LPA Gene Variant May Help Identify Increased Risk of Aortic Stenosis 

MedicalResearch.com Interview with:

Aortic Stenosis Blaus Image Wikipedia

Aortic Stenosis Blaus Image Wikipedia

Hao Yu Chen, MSc
Department of Medicine
McGill University
Montreal, Quebec, Canada
Senior author: George Thanassoulis, MD, MSc

MedicalResearch.com: What is the background for this study?

Response: Aortic stenosis, a narrowing of the main valve of the heart, is the most common type of valve disease in the US. Present in more than 2.5 million individuals in North America, aortic stenosis can lead to heart failure and death. However, there is little known about the causes of aortic stenosis and how it should be treated.

Previously, we have demonstrated that variants of the gene LPA are associated with the development of aortic stenosis. A better understanding of how this region contributes to aortic stenosis could identify higher-risk individuals and inform the development of new medical therapies for aortic stenosis.  Continue reading

Mechanism Identified Linking ASD and Intellectual Disability, Opening Door To Development of Treatment Options

MedicalResearch.com Interview with:

Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience  Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960

Dr-Woo-Yang Kim

Woo-Yang Kim, Ph.D
Associate Professor
Department of Developmental Neuroscience
Munroe-Meyer Institute
University of Nebraska Medical Center
Omaha, NE 68198-5960

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions.

Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown.

Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes.

Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability.

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Improved DNA Analysis Reduces False Positive Prenatal DNA Testing For Trisomy Conditions

MedicalResearch.com Interview with:

Professor Sir Nicholas Wald FRCP FRS Professor of Preventive Medicine Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary University of London London

Prof. Wald

Professor Sir Nicholas Wald FRCP FRS
Professor of Preventive Medicine
Wolfson Institute of Preventive Medicine
Barts and The London School of Medicine and Dentistry
Queen Mary University of London
London

MedicalResearch.com: What is the background for this study?

Response: Prenatal screening for Down’s syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) by maternal plasma DNA analysis has an improved screening performance compared with conventional screening but is too expensive to be performed routinely and has a technical failure rate.

The aim of the study was to take advantage of the improved screening performance of the DNA analysis in conjunction with the existing methods thereby providing a seamless testing interface between the “old” and the “new” methods that would detect a larger proportion of affected pregnancies with a much lower false-positive rate, at a much reduced cost compared with universal DNA testing and with no failed tests. The novel approach was to conduct a conventional screening test using a screening cut-off level that identifies about 10% of women with the highest risks of having an affected pregnancy (much higher than in conventional screening) and then to perform a DNA test using a portion of the original blood sample collected for the conventional test. Progressing to the DNA test was automatic for these high risk women without their having to be recalled for counseling and a fresh blood sample (ie as a reflex response hence the term “reflex DNA screening”).

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FDA Advisory Committee Recommended Approval of First Gene Therapy For Inherited Eye Disease

MedicalResearch.com Interview with:
Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting BlindnessDr. Stephen M. Rose, PhD
Chief Research Officer
Foundation Fighting Blindness

Dr. Rose discusses the FDA advisory panel unanimously recommended approval of Spark Therapeutics’ Gene Therapy Luxturna  for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal dystrophies, a group of rare blinding conditions caused by one of more than 220 different genes.

MedicalResearch.com: Would you tell us a little about IRD? Whom does it affect and how?  How common is this disorder?

Response: The retina at the back of the eye is responsible for collecting light and turning it into signals that are transmitted to the brain and interpreted as vision. Think of the retina as the film in a camera, or more recently the sensor at the back of a digital camera. Inherited rare retinal degenerations are when the retina at the back of the eye deteriorates and loses its ability to capture light, thereby leading to blindness.

iRDs can affect anyone, no matter race or ethnicity. These are inherited conditions that are passed down from parents to children, if a parent or both parents are either affected already or are carriers for a variant in any of the over 250 genes responsible for retinal degeneration.

There are over 15 different types of iRDs, with retinitis pigmentosa being the most common with a US affected population around 100,000. The rest of the iRDs make up another approximately 100,000 affected individuals in the US, so there are about 200,000 total affected individuals in the US. Worldwide these iRDs affect somewhere around one to two million individuals.

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Single Injection of Klotho Gene Protected Animals From Cognitive Decline

MedicalResearch.com Interview with:

Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain

Dr. Chillon

Dr Miguel Chillon PhD
Department of Biochemistry and Molecular Biology
Universitat Autonoma Barcelona
Spain

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer’s disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer’s patients than in human controls of the same age; and it is lower in the elderly with respect to young adults.

Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho.

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Failure of Dental Fillings Is At Least Partially Genetically Determined

MedicalResearch.com Interview with:
“Dental Mold_002” by Ano Lobb is licensed under CC BY 2.0
Alexandre R. Vieira, DDS. MS, PhD
Professor, Director of Clinical Research,  Director of Student Research
Department of Oral Biology
Center for Craniofacial and Dental Genetics
Department of Pediatric Dentistry
School of Dental Medicine
Department of Human Genetics
Graduate School of Public Health
Clinical and Translational Sciences Institute
University of Pittsburgh 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One aspect is the dilemma between continuing to use dental amalgams and the perception that composite resins are not as durable.

We show that composite resin restorations can perform similarly to dental amalgams for the first 5 years. But the most remarkable is that composite resin failures may be related to certain individual risk factors, such as genetic variation.

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With Aging, Males and Females Express Genes Differently

MedicalResearch.com Interview with:
Dr Mandy Peffers BSc MPhil PhD BVetMed FRCVS
Wellcome Trust Clinical Intermediate Fellow
Institute of Ageing & Chronic Disease
Faculty of Health & Life Sciences
University of Liverpool Liverpool UK

MedicalResearch.com: What is the background for this study?

Response: The project was an extension of Louise Pease’s MSc research project in bioinformatics which aimed to re-analyse existing RNA-seq data to determine age related changes in gene expression in musculoskeletal tissues that may lead to the development of degenerative diseases.  From existing literature we identified that degenerative diseases such as osteoarthritis and tendinitis were more prevalent in females and became more frequent following menopause.  We looked at the biology of the cohort we were trying to assess and discovered a gender imbalance, we hypothesised that this was why few results had been obtained from the original analysis. So we developed a research proposal that detailed extending the existing data to publicly available data and merging the experiments; to increase the number of replicates available and balance the experimental design.  We conducted multiple analyses and discovered that splitting samples by age and gender obtained the most significant results, and that whilst in a lot of cases the same genes were being differentially expressed, they were changing in opposite directions.  Louise remembered her statistics lecturer Gerard Cowburn (Ged) taught her about the assumptions of statistical tests, in particular covariance analysis (which has previously been used to show that age and gender do not affect gene expression) assumed that under the conditions being tested data points were not opposites.  Realising that this assumption had been violated by the data she began to think about what other assumptions we were working with and how to test their validity.

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Complexity of Animals Depends On Diverse Patterns of Gene Regulation

MedicalResearch.com Interview with:
Colin Sharpe

School of Biology
Institute of Biomolecular and Biomedical Science
School of Biological Sciences
University of Portsmouth
Portsmouth, United Kingdom 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have long been fascinated by the question of what underpins the increasing complexity of multicellular animals. In a recent publication we looked at changes to the diversity of the NCoR family corepressors (NCoRs) across the Deuterostomes and found an increase in diversity from sea urchins to humans (1). This is due to gene duplication, an increase in alternative splicing and the encorporation of more protein motifs and domains.

In this study we devised a measure of functional diversity based on these three factors and calculated this value for over 12000 genes involved in transcription in nine species from the nematode worm to humans. Orthologues whose increase in diversity correlated with the increase in complexity of these animals were then selected and we looked for common features and interactions between the selected genes.

We found that proteins that regulate the dynamic organisation of chromatin were significantly enriched within the selection.

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Genetic Testing Reduces Risk Of Side Effects From Anticoagulation After Surgery

MedicalResearch.com Interview with:

Anne R. Bass, MD Associate Professor of Clinical Medicine Weill Cornell Medical College Rheumatology Fellowship Program Director Hospital for Special Surgery New York, NY 10021

Dr. Bass

Anne R. Bass, MD
Associate Professor of Clinical Medicine
Weill Cornell Medical College
Rheumatology Fellowship Program Director
Hospital for Special Surgery
New York, NY 10021

MedicalResearch.com: What is the background for this study?

Response: Blood thinners are used after orthopedic surgery to prevent blood clots from forming in the legs and traveling to the lungs. They are also used in patients with certain heart diseases to prevent strokes. Blood thinners, like warfarin, are effective but can be associated with serious bleeding complications, especially if the wrong dose is given. Genetic testing can help doctors predict the right warfarin dose to use in an individual patient.

In this trial, ≈1600 elderly patients undergoing hip or knee replacement were randomly assigned to receive warfarin dosing based on genetics plus clinical factors (like height, weight and gender), or based on clinical factors alone. The specific genes tested wereVKORC1, CYP2C9, and CYP4F2 which influence warfarin metabolism and the body’s ability to produce clotting factors.

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Despite Evolution, Genetic Diseases Persist

MedicalResearch.com Interview with:

Carlos Eduardo G. Amorim PhD Columbia University Department of Systems Biology Irving Cancer Research Center

Dr. Amorim

Carlos Eduardo G. Amorim PhD
Columbia University Department of Systems Biology
Irving Cancer Research Center 

MedicalResearch.com: What is the background for this study?

Response: More generally, we were interested in understanding the determinants of the frequencies of mutations that cause disease in humans.

More specially, we wanted to test if a long-standing theory in population genetics (namely mutation-selection balance) was a good explanation for the observed frequencies of disease mutations in humans.

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Autism Spectrum Disorder Found To Be Highly Heritable

MedicalResearch.com Interview with:

Sven Sandin, PhD Assistant Professor Department of Psychiatry Icahn School of Medicine at Mount Sinai New York, NY 10029

D. Sandin

Sven Sandin, PhD Assistant Professor
Department of Psychiatry
Icahn School of Medicine at Mount Sinai
New York, NY 10029 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In 2014, we estimated the heritability of autism to be approximately 50%. Motivating us then was the lack of studies in autism heritability using population based and the findings from a twin-study in California finding the heritability to be substantially lower than the 80-90% estimated in previous studies. Since then continued efforts working with the questions on heritability and environmental factors for autism we found differences between different methods and different samples. When we went back to our previous data we found the heritability of autism to be higher than previously estimated. We found that our previous result was due to a methodological artifact where the adjustment for differences in follow-up used in that manuscript underestimated the heritability. Using methods used in other heritability studies the heritability is now estimated to 84%. Importantly, as previously concluded, there is no support for any ‘shared environmental factors’ in the etiology of autism, e.g. environmental factors shared between two siblings.

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Facial Structure Linked To Sexual Drive and Orientation

MedicalResearch.com Interview with:

Steven Arnocky PhD Faculty of Arts & Science-Psychology Nipissing University Canada

Dr. Arnocky

Steven Arnocky PhD
Faculty of Arts & Science-Psychology
Nipissing University
Canada 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  – Previous research has linked the facial width-to-height ratio to a number of testosterone-mediated traits, primarily in men, such as aggression and achievement drive. Some research has also linked FWHR to testosterone directly, although this research is less consistent. If testosterone is linked to cranio-facial development then we hypothesized that facial masculinization should therefore correlate with other testosterone-linked traits. In both men and women, there is good evidence that testosterone increases sexual motivation.

In two samples of young-adults from two Canadian cities, we found that  facial width-to-height ratio predicted sex-drive, regardless of whether participants were male or female.

In the second study (the larger of the two) we also found that FWHR predicted a more unrestricted sociosexual orientation, in other words, attitudes and behavior consistent with more pluralistic mating, as well as more intended infidelity.

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Pandemic Flu May Increase Risk of Type 1 Diabetes In Genetically Predisposed Patients

MedicalResearch.com Interview with:
Paz Lopez-Doriga Ruiz MD, PhD candidate Norwegian Institute of Public Health Department of Non Communicable Diseases OsloPaz Lopez-Doriga Ruiz MD, PhD candidate

Norwegian Institute of Public Health
Department of Non Communicable Diseases
Oslo 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Some case reports have linked pandemic influenza to the development of type 1 diabetes. Other studies have suggested that also respiratory infections may contribute to type 1 diabetes risk.

 Our findings supports a suggested role of respiratory infections in the etiology of type 1 diabetes and influenza virus could be a contributing factor to the development of clinical diabetes, due to stress and inflammation in predisposed individuals.

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Tall Height Is a Risk Factor For Venous Thromboembolism

MedicalResearch.com Interview with:
Bengt Zöller, MD, PhD
Associate professor in Internal Medicine
Specialist Physician in Clinical Chemistry
Specialist Physician in Family Medicine
Lund University/ Region Skåne
Center for Primary Health Care Research
University Hospital, Malmö, Sweden

MedicalResearch.com: What is the background for this study?

Response: Previous studies have suggested an association between height and venous thromboembolism but association might be confounded. We therefore permed a Nationwide study including a cohort of siblings -a co sibling analysis to adjust for familial confounders (genetic and shared familial environmental factors).

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Study Opens Door To Reducing Melanoma Risk in Redheads

MedicalResearch.com Interview with:

Rutao Cui, MD/PhD Professor  Vice Chair for Laboratory Administration  Director, Laboratory of Melanoma Biology Department of Pharmacology and Experimental Therapeutics Professor of Dermatology Boston University Boston, Mass 02118

Dr. Cui

Rutao Cui, MD/PhD
Professor
Vice Chair for Laboratory Administration
Director, Laboratory of Melanoma Biology
Department of Pharmacology and Experimental Therapeutics
Professor of Dermatology
Boston University
Boston, Mass 02118


MedicalResearch.com: What is the background for this study?

Response: Red-headed people are making up to 1~2% of the world’s population. They carry “red hair color” variants of MC1R (MC1R-RHC) which are responsible for their characteristic features, including red hair, pale skin, freckles and poor tanning ability.

MC1R-RHC also increases risk of melanoma, the deadliest form of skin cancer. People without red hair but with a single copy of MC1R-RHC also have an increased melanoma risk, who may make more than 50% of the northern European population. It is unknown why redheads are more prone to melanoma, and whether the activity of red hair color variants could be restored for therapeutic benefits.

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Genetic Variants Demonstrate Humans Continue To Evolve Through Natural Selection

MedicalResearch.com Interview with:

Hakhamanesh Mostafavi, MS PhD student Department of Chemical Engineering Columbia University

Mostafavi Hakhamanesh

Hakhamanesh Mostafavi, MS
PhD student
Department of Biological Sciences
Columbia University 

MedicalResearch.com: What is the background for this study?

Response: We know very little about the genetic variants that underlie adaptation in humans. This is in part because we have mostly been limited to methods that search for footprints of ancient selection (that has acted for over thousands to millions of years) in the genomes of present-day humans; so by design are indirect and make strong assumptions about the nature of selection.

These days, thanks to advances in genomic technologies, genetic data for large numbers of people is being collected, mostly for biomedical purposes. Accompanied by information on survival and reproductive success of these individuals, such large datasets provide unprecedented opportunities for more direct ways to study adaptation in humans.

In this work, we introduced an approach to directly observe natural selection ongoing in humans. The approach consists in searching for mutations that change in frequency with the age of the individuals that carry them, and so are associated with survival. We applied it to around 210,000 individuals from two large US and UK datasets.

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Gene Helps Explain Why More Women Than Men Have Alzheimer’s

MedicalResearch.com Interview with:

Arthur W. Toga PhD Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences, Radiology and Engineering Ghada Irani Chair in Neuroscience Director, USC Mark and Mary Stevens Neuroimaging and informatics institute USC Institute for Neuroimaging and Informatics Keck School of Medicine of USC University of Southern California Los Angeles, CA  90032

Dr. Toga

Arthur W. Toga PhD
Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences,
Radiology and Engineering
Ghada Irani Chair in Neuroscience
Director, USC Mark and Mary Stevens Neuroimaging and informatics institute
USC Institute for Neuroimaging and Informatics
Keck School of Medicine of USC
University of Southern California
Los Angeles, CA  90032 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The ε4 allele of the Apolipoprotein E (APOE) gene is the main genetic risk factor for late-onset Alzheimer’s disease.  This study reexamines and corrects the sex-dependent risks that white men and women with one copy of the ε4 allele face for developing Alzheimer’s disease using a very large data set of 57,979 North Americans and Europeans from the Global Alzheimer’s Association Interactive Network (GAAIN).

The study results show that these men and women between the ages of 55 and 85 have the same odds of developing Alzheimer’s disease, with the exception that women face significantly higher risks than men between the ages of 65 and 75.  Further, these women showed increased risk over men between the ages of 55 and 70 for mild cognitive impairment (MCI), which is often a transitional phase to dementia.

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Familial Hypercholesterolemia: “Junk” RNA May Facilitate Gene Therapy

MedicalResearch.com Interview with:

Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 

Dr. Sallam

Tamer Sallam, MD PhD
Assistant Professor of Medicine
Co-Director UCLA Center for Lipid Management
Lauren B. Leichtman and Arthur E. Levine CDF Investigator
Assistant Director, STAR Program
Division of Cardiology, Department of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, California 90095-1679

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease.

In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases.

Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments.

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DNA Analysis Identifies Subtype of Pancreatic Cancer With Good Prognosis

MedicalResearch.com Interview with:

Nancy You, MD, MHSc, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston

Dr. You

Nancy You, MD, MHSc, FACS
Department of Surgical Oncology
The University of Texas MD Anderson Cancer Center
Houston 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study was motivated by the emerging promise of precision medicine and the emerging evidence that immunotherapy may have phenomenal efficacy in particular molecular subtypes of cancers.  This specific molecular subtype shows deficiency in DNA mismatch repair mechanisms and therefore is thought to be more immunogenic.  DNA mismatch repair deficiency can arise from germline defects such as in the case of patients with Lynch Syndrome, an inherited cancer syndrome, or from epigenetic inactivation DNA mismatch repair genes.

Overall, pancreas cancer has seen limited success with conventional chemotherapy.  In our study, we demonstrated that there is a particular molecular subtype of pancreas cancer that is characterized by defect in DNA mismatch repair genes and by microsatelie instability that has a different prognosis than other pancreas cancers.  This subtype of pancreas cancer is suspected to also respond to immunotherapy.

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16 New Genetic Links To Longevity Discovered

MedicalResearch.com Interview with:

Dr. Zoltán Kutalik, PhD Group Leader Swiss Institute of Bioinformatics

Dr. Kutalik

Dr. Zoltán Kutalik, PhD
Group Leader
Swiss Institute of Bioinformatics
Assistant professor at the Institute of Social and Preventive Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Why do some of us live longer than others? While the environment in which we live – including our socio-economic status or the food we eat – plays the biggest part, about 20 to 30% of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity. Until now, the most comprehensive studies had found only two hits in the genome.

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One Time Injection With Spark’s Gene Therapy LUXTURNA Demonstrated Lasting Visual Improvement

MedicalResearch.com Interview with:

Stephen R. Russell, MD Dina J Schrage Professor of Macular Degeneration Research Service Director, Vitreoretinal Diseases and Surgery Professor of Ophthalmology and Visual Sciences The University of Iowa

Dr. Russell

Stephen R. Russell, MD
Dina J Schrage Professor of Macular Degeneration Research
Service Director, Vitreoretinal Diseases and Surgery
Professor of Ophthalmology and Visual Sciences
The University of Iowa

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study examines the efficacy (and safety) of treating children and adults with a form of retinitis pigmentosa known as RPE65-associated Lebers congenital amaurosis, with an adeno-associated viral vector(AAV) delivered RPE65 construct.  Building on successful phase 1/2b trials from multiple centers, the AAV-hRPE65v2 agent now designated as voretigene neparvovec, contains a highly optimized enhancing sequence and promoter.

The main findings were an improvement on a multiple light level mobility test (MLMT) and multiple additional supportive secondary endpoints which included improvements in full-field light sensitivity, Goldmann visual field, and others.

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New Gene Mutation Found to Cause Retinitis Pigmentosa in SW USA Hispanics

MedicalResearch.com Interview with:

Stephen P. Daiger, PhD TS Matney Professor of Environmental and Genetic Sciences Human Genetics Center, School of Public Health and Mary Farish Johnston Distinguished Chair of Ophthalmology Ruiz Dept. of Ophthalmology and Visual Science The Univ. of Texas HSC at Houston

Dr. Daiger

Stephen P. Daiger, PhD
Professor, Human Genetics Center
Thomas Stull Matney, Ph.D. Professor in Environmental and Genetic Sciences
Mary Farish Johnston Distinguished Chair in Ophthalmology
The University of Texas Health Science Center at Houston

 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Thanks for your questions about our research.  My research group and I have a long-term interest in finding genes and mutations causing inherited retinal diseases.  Our main focus is on retinitis pigmentosa (RP) and, more specifically, the autosomal dominant form of RP.

Inherited retinal diseases are progressive, degenerative diseases of the retina.  Onset can be very early in life, even at birth, or much later in life.  As the degeneration develops an affected person may first experienced limited loss of vision, progressing to severe loss of vision, ending, in many cases, in legal or complete blindness.  About 300,000 Americans are affected by inherited retinal disease and 50% of these have RP.  RP, like most hereditary conditions, can be inherited in an autosomal dominant, autosomal recessive or X-linked fashion.

One of the surprising, and in some sense, disturbing findings in studying  retinitis pigmentosa is that mutations in many different genes can cause this disease.  We now know that mutations in more than 80 genes can cause RP and thousands of different mutations have been found in these genes.  With next-generations sequencing it is possible to find the cause of RP in from 50% to 80% of cases, depending on the underlying mode of inheritance.For example, in our research we can find the disease-causing mutation in about 75% of families with autosomal dominant RP.  Needless to say, a primary aim of our research is to find the cause in the remaining 25%.

In looking for the cause of retinitis pigmentosa in the remaining 25%, that is, those in whom mutations were not detected by earlier methods, we found a potential dominant-acting mutation in the arrestin-1 gene (gene symbol “SAG”) using whole-genome sequencing.  Molecular modeling suggests this mutation is damaging.  This was unexpected because previously-reported mutations in this gene were associated with Oguchi disease, a recessive retinal disease with symptoms distinct from RP.  On further testing our cohort of patients with autosomal dominant RP, we found this mutation in nearly 4% of families.  Even more surprisingly, when we looked closely at the affected families, and worked with our collaborators to test other patients, we discovered that all of the families with the dominant-acting SAG mutation — 12 total — were of Hispanic origin.  By interviewing informative family members we learned that these families have their roots in the Southwestern United States.  Historically, the mutation may have arisen hundreds of years ago, consistent with genetic variation tracking with the mutation.

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Study Finds Link Between Genetic Variant, Opioid Addiction and Binge Eating

MedicalResearch.com Interview with:

Camron D. Bryant Ph.D Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry Boston University, Boston, MA

Dr. Bryant

Camron D. Bryant Ph.D
Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry
Boston University, Boston, MA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We previously used genome-wide linkage analysis, fine mapping, gene validation, and pharmacological targeting to identify a negative regulatory role for the gene casein kinase 1-epsilon (Csnk1e) in behavioral sensitivity to drugs of abuse, including psychostimulants and opioids.

Parallel human candidate genetic association studies identified an association between multiple genetic variants in CSNK1E with heroin addiction in multiple populations. Drug addiction is a multi-stage process that begins with the initial acute subjective and physiological responses that can progress to chronic administration, tolerance, and withdrawal. The recovery process begins with abstinence from drug taking but can quickly be derailed by relapse to drug taking behavior. Preclinical pharmacological studies also support a role for CSNK1E in reinstatement of opioid self-administration and relapse to alcohol drinking.

Despite the evidence that disruption of Csnk1e gene and protein function can affect various behaviors associated with drug and alcohol addiction, it is unclear what stage of the addiction process these genetic and pharmacological manipulations modulate. In this study, we show that disruption of the Csnk1e gene resulted in an enhancement of the rewarding properties of the highly potent and addictive opioid, fentanyl.  Unexpectedly, we also discovered that disruption of Csnk1e also enhanced binge eating – but only in female mice.

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Gene Linked To Decreased Plasma Amyloid and Lower Alzheimer’s Disease Risk

MedicalResearch.com Interview with:

Mikko Hiltunen, PhD Professor of Tissue and Cell Biology University of Eastern Finland School of Medicine, Institute of Biomedicine Kuopio,  Finland

Dr. Hiltunen

Mikko Hiltunen, PhD
Professor of Tissue and Cell Biology
University of Eastern Finland
School of Medicine, Institute of Biomedicine
Kuopio,  Finland 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  We wanted to assess among the population-based METSIM (METabolic Syndrome In Men) cohort whether protective variant in APP gene (APP A673T) affects the beta-amyloid levels in plasma. The rationale behind this was that previous genetic studies have discovered that the APP A673T variant decreases the risk of having Alzheimer’s disease (AD).

However, the protective functional outcome measures related to this variant were lacking and thus we anticipated that the elucidation of plasma samples in terms of beta-amyloid levels would provide the much needed link between APP A673T variant and potential protective functions.

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Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

MedicalResearch.com Interview with:

Antonis Antoniou PhD Reader in Cancer Risk Prediction Academic Course Director MPhil in Epidemiology Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge University of Cambridge

Dr. Antoniou

Antonis Antoniou PhD
Reader in Cancer Risk Prediction
Academic Course Director MPhil in Epidemiology
Centre for Cancer Genetic Epidemiology
Department of Public Health and Primary Care
Strangeways Research Laboratory Cambridge
University of Cambridge

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Several studies demonstrated that women with genetic faults in the BRCA1 and BRCA2 genes are at increased risk of developing breast and ovarian cancer. Having accurate age-specific cancer risk estimates for women with mutations is essential for their optimal clinical management.

Most studies to date that estimated cancer risks for BRCA1 and BRCA2 mutation carriers have been “retrospective”, in other words they look at what happened in the past. Estimates from such studies are prone to biases because they rely on the experience of women who have already developed cancer and on self-reported cancer family history information on relatives – which may have inaccuracies.

The ideal epidemiological study design for estimating cancer risks are prospective studies.  In prospective studies, healthy women with genetic faults are followed over time and overcome these potential biases. However, to date, published  prospective studies have been very small.

In the present study we used data from a prospective cohort of women with BRCA1 and BRCA2 mutations who were recruited from 1997 to 2011 and were followed over time. The study included almost 10,000 women who were included in the analyses, and was made possible through collaborations between scientists from Europe, North America and Australia.  The prospective study design explains why it has taken 20 years of hard work to get these results. Most importantly, it took an enormous long-term contribution and commitment from the women themselves to allow the scientists to be able to assemble this dataset.

Here, we were able to estimate more precisely the breast and ovarian cancer risks for women with faults in BRCA1 and BRCA2.  These risk estimates will provide more confidence in the counseling and clinical management of women with faults in the BRCA1 and BRCA2  genes.

A novel finding in this study is that breast cancer risk for women with faults in BRCA1 and BRCA2  increases rapidly at a young age then remains at a constant high level for the rest of their lives. It peaks in the 40’s for BRCA1 mutation carriers and in the 50’s for BRCA2 carriers, but  carriers of mutations in both genes  are at about the same high risk in later life. This is important information to inform the clinical management of older mutation carriers.

This study also shows clearly that for women with a mutation, there are other factors that are important in modifying the breast cancer risk. The study has demonstrated that the extent of the woman’ family history of cancer and the exact place on the gene where her mutation is located are very important in determining the actual risk.

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Rapid Improvements Coming to Gene Editing Techniques

MedicalResearch.com Interview with:

Michael Farzan PhD Co-chair and Professor Department of Immunology and Microbiology  Florida Campus  The Scripps Research Institute Jupiter, Florida

Dr. Farzan

Michael Farzan PhD
Co-chair and Professor
Department of Immunology and Microbiology
Florida Campus
The Scripps Research Institute
Jupiter, Florida

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: CRISPR is system for immune protection of bacteria.  It has now been widely adopted for use in editing mammalian cells.  The most commonly used CRISPR effector protein is Cas9.  Cas9 binds a guide RNA to recognize a DNA target, for example an incoming virus infecting a bacterium, or a gene in a human chromosome.  In bacteria, Cas9 requires a second protein to clear the guide RNA from a longer “CRISPR array”, basically a string of guide RNAs.

We have been studying a CRISPR effector protein related to Cas9 called Cpf1.  In bacteria it was know that, unlike Cas9, Cpf1 could cleave a CRISPR array by itself, without assistance from a second protein.  We knew that if it could do the same thing in human cells, it would help to simplify a number of gene-editing applications.  We were able to show that Cas9 could indeed excise multiple guide RNAs from a single message RNA in human cells.  We further showed that this approach was more efficient than the previous ways that guide RNAs were generated for gene editing, even more so when multiple guide RNAs were needed.

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Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing’s disease

MedicalResearch.com Interview with:

Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda

Dr. Stratakis

Constantine A. Stratakis, MD, DMSci
Section on Endocrinology and Genetics
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health, Bethesda

MedicalResearch.com: What is the background for this study?

Response: The pituitary and adrenal glands operate on a kind of feedback loop. In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol. Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease.

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Mind–Body Interventions Reduce Inflammatory Activity of Genes

MedicalResearch.com Interview with:

Ivana Buric Brain, Belief, and Behaviour Lab Centre for Psychology, Behaviour, and Achievement, Faculty of Health and Life Sciences Coventry University, Coventry, United Kingdom Donders Institute for Brain, Cognition and Behaviour Radboud University, Nijmegen, Netherlands

Ivana Buric

Ivana Buric
Brain, Belief, and Behaviour Lab
Centre for Psychology, Behaviour, and Achievement, Faculty of Health and Life Sciences
Coventry University, Coventry, United Kingdom
Donders Institute for Brain, Cognition and Behaviour
Radboud University, Nijmegen, Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Genes that we inherited can change their activity – the​y can be active and produce proteins, but they can also stop producing proteins and remain silent. We are now beginning to understand what aspects of our environment affect the activity of which genes.

In this study, we analysed all the existing studies that examined the effects of mind-body interventions on the expression of our genes and found that mind-body techniques reduce the activity of genes that produce inflammatory proteins.

This pattern was found in all studies despite the fact that they vary in the amount of physical activity: Tai Chi, yoga, breathing techniques and different types of meditation. We believe that this effect is observed due to reduced stress.

When we experience something stressful, the brain regions associated with pain get activated and send that signal further to sypmathetic nervous system that produces epinephrine and norepinefrine, and activates nuclear factor kappa B – a molecule that travels to and activated the genes that produce inflammatory proteins. When we do yoga or meditation, we learn to perceive situations differently and consequently experience less stress, which then prevents the production of inflammatory proteins.

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Genetic Cause of Cushing’s Disease Detected

MedicalResearch.com Interview with:

Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda

Dr. Stratakis

Constantine A. Stratakis, MD, DMSci
Section on Endocrinology and Genetics
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health, Bethesda 

MedicalResearch.com: What is the background for this study?

Response: The pituitary and adrenal glands operate on a kind of feedback loop.  In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol.  Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease.

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Which Diet Is Best For You? It Depends On Your Genes

MedicalResearch.com Interview with:

Kaixiong (Calvin) Ye, PhD Post-doctoral Associate Dept. of Biological Statistics & Computational Biology Cornell University thaca, NY

Dr. Kaixong Ye

Kaixiong (Calvin) Ye, PhD
Post-doctoral Associate
Dept. of Biological Statistics & Computational Biology
Cornell University
thaca, NY

MedicalResearch.com: What is the background for this study?

Response: Omega-6 and omega-3 fatty acids are critical for human brain development, cognitive function, immune response, and cardiovascular health. Physiologically active forms of omega-6 and omega-3 fatty acids, such as AA, EPA, and DHA, are readily available in meat and seafood, but are absent in most plant-based foods (e.g. fruits and vegetables). Instead, plant-based foods contain two precursor fatty acids, LA and ALA, which could be metabolized in our body and converted into physiologically active forms. Fatty acid desaturase (FADS) genes encode key enzymes for this biosynthesis.

We hypothesized that genetic variations in FADS genes that enhance the biosynthesis efficiency were adaptive to plant-based diets in traditional farming populations and thus became more frequent over time. Our study compiled a huge data set of genetic information (DNA) from both present-day and ancient individuals. For the first time, we examined the action of natural selection on humans for the past 30,000 years in Europe.

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Epigenetic Changes Identified In Children Who Develop Early Onset Conduct Problems

MedicalResearch.com Interview with:
Charlotte Cecil, PhD

ESRC FRL Fellow
Edward Barker, PhD
Lab Director, DEVELOPMENTAL PSYCHOPATHOLOGY LAB

Department of Psychology
Institute of Psychiatry, Psychology& Neuroscience
King’s College London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Conduct problems (CP) are the most common reason for child treatment referral in the UK, costing an estimated £22 billion per year. Children with CP engage in a range of aggressive and antisocial behaviours (e.g. fighting, stealing, lying), that affect their ability to follow rules and adapt to society, do well in school, and form healthy relationships. Those who do not receive treatment are also at increased risk for many negative outcomes in adulthood, including lower job prospects and earnings, more contact with the police and a lower quality of life. Therefore, it is important to understand how CP develop in the first place, in order to create more effective prevention and intervention strategies.

Studies have found that children who develop conduct problems before the age of 10 (early-onset CP) are at greatest risk for poor outcomes across the lifespan. Compared to other children, those showing early-onset CP tend to have experienced more adversity in early life (e.g. prenatal stress, poverty) as well as having more genetic risk. However, little is known about about how genetic factors interact with environmental influences – especially during foetal development – to increase the risk for early-onset conduct problems.

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Genetic Cause and Clinical Cure Found For Rare Skin Disorder

MedicalResearch.com Interview with:

Keith Adam Choate, MD, PhD, FAAD Associate Professor of Dermatology, of Genetics and of Pathology Director of Research, Dermatology Yale University School of Medicine New Haven, CT

Dr Choate

Keith Adam Choate, MD, PhD, FAAD
Associate Professor of Dermatology,
Genetics and Pathology
Director of Research, Dermatology
Yale University School of Medicine
New Haven, CT

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Over the last 10 years, we have systematically been examining patients with ichthyosis to identify new genetic causes of this group of disorders.  We found that autosomal recessive mutations in KDSR cause ichthyosis and that the resulting skin disease is effectively treated with isotretinoin.

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Gene Dosage at 22q11.2 Helps Determine Schizophrenia vs Autism Brain Differences

MedicalResearch.com Interview with:

Carrie Bearden, Ph.D. Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology Semel Institute for Neuroscience and Human Behavior University of California, Los Angeles

Dr. Bearden

Carrie Bearden, Ph.D.
Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology
Semel Institute for Neuroscience and Human Behavior
University of California, Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population.

Thus, we became interested in trying to understand whether there were differences in brain development that might predispose to one condition vs. the other.

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Familial History Improves Predictive Value of TOMM40 Gene in Alzheimer’s Disease

MedicalResearch.com Interview with:

Auriel Willette, M.S., Ph.D. Assistant Professor Departments of Food Science and Human Nutrition and Psychology Iowa State University

Dr. Willette

Auriel Willette, M.S., Ph.D.
Assistant Professor
Departments of Food Science and Human Nutrition and Psychology
Iowa State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is a gene that regulates the width of the outer mitochondrial pore, facilitating the transport of ribosomal pre-proteins into the inner mitochondrial matrix for translational modification into functional proteins. In 2010, Dr. Allen Roses, who discovered the Apolipoprotein E (APOE) gene, Dr. Michael Lutz, and other colleagues found that a variation in poly-T length at locus rs10524523 (‘523) within intron 6 predicted Alzheimer’s disease onset. Specifically, a “long” versus “short” poly-T length was related to earlier age of onset by 8 years.

However, several multi-cohort studies either failed to replicate the findings or found the opposite relationship, where a “long” or “very long” poly-T length was related to later age of onset. The literature has remained mixed to this day.

We were interested in testing factors that might change the relationship between TOMM40 and both cognitive decline and risk for having Alzheimer’s disease. It is known that a family history (FH) of Alzheimer’s disease has been associated with mitochondrial dysfunction. We reasoned, then, that FH may interact with TOMM40 to modulate how it was related to our outcomes of interest. We investigated this hypothesis in two separate cohorts: the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a late middle-aged cohort, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a well-characterized sample of aged participants from across the Alzheimer’s spectrum.

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Genomic Profile Can Improve Confidence in Active Surveillance of Prostate Cancer

MedicalResearch.com Interview with:

Bela S. Denes, MD, FACS Senior Director Medical Affairs UROLOGY Genomic Health Inc. Redwood City, CA. 94063

Dr. Bela S. Denes

Bela S. Denes, MD, FACS
Senior Director Medical Affairs
UROLOGY
Genomic Health Inc.
Redwood City, CA. 94063

MedicalResearch.com: What is the background for this study?

Response: This is a prospective community based non-interventional study designed to provide information on the utility of Oncotype GPS in the management of men presenting with a new diagnosis of clinically localized low risk prostate cancer. We sought to understand the impact of incorporating a molecular marker into the shared treatment decision in practices already well versed in Active Surveillance (AS) as measured by persistence on surveillance at 2 years as well as a number of patient reported outcomes. The current publication reports on the results of a one year pre-specified interim analysis.

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Malignancies More Common In Men With BRCA Germline Mutations

MedicalResearch.com Interview with:
Roy Mano, MD and
David Margel, MD, PhD
Department of Urology, Rabin Medical Center
Petach Tikva, Israel

MedicalResearch.com: What is the background for this study?

Response: According to previous reports, male BRCA mutation carriers have a higher risk of developing malignancies of the prostate, pancreas, breast, colon and melanoma. While malignancy screening protocols for female BRCA carriers are well established and widely implemented, little is known about the optimal screening protocol for male BRCA carriers, and current screening protocols focus on malignancies of the breast and prostate rather than offer a comprehensive screening protocol for all BRCA associated malignancies.

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TeloView Measures Genomic Stability To Predict Disease Aggressiveness

MedicalResearch.com Interview with:

3D SignaturesJason Flowerday, CEO
Director of 3D Signatures 

MedicalResearch.com: What is the background for 3D Signatures?

Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level.

By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date.

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Gene Delivered By Nanoparticle System Can Potentially Cure Congenital Blindness

MedicalResearch.com Interview with:
Zheng-Rong Lu, Ph.D.

M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering
Department of Biomedical Engineering
Case Western Reserve University
Cleveland, OH 44106

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders.

This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered.

In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder.

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Gene-silencing RNAs Targeting CTNNB1 and PD-L1 May Attack a Variety of Cancers

MedicalResearch.com Interview with:
Dr. Youzhi Li

Vice President at Boston Biomedical 

MedicalResearch.com: What are the main findings?

Response: RNAi (RNA interference) technology has the potential to target any genes causing disease, including conventionally “undruggable” targets in cancer. One particularly interesting RNAi target in oncology is the CTNNBI oncogene, which encodes the β-Catenin protein whose nuclear form acts as a transcription factor promoting tumorigenesis. Aberrant β-Catenin signaling has been demonstrated in 90 percent of colorectal carcinomas, 40 percent of hepatocellular carcinoma, and 90 percent of non-ductal pancreatic carcinomas. Recent research also suggests active β-Catenin contributes to tumor immune evasion and to the recurrence of melanoma in patients post the check-point blockage immunotherapy.

However, the direct blockade of β-Catenin activity has proved difficult with conventional approaches. While the application of traditional RNAi technology has the potential to block this pathway, in clinical cancer therapy, this approach has proven challenging due to the difficulty in systemic delivery of RNAi to tumor sites located in various organs.

We have recently developed BBI-801, a lipid-based nanoparticle that encapsulates therapeutic aiRNAs targeting CTNNB1 and PD-L1 to simultaneously target immune evasion via both these pathways. Here, we investigate the in vivo delivery and anti-tumor activity of BBI-801.

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Do Our Genes Influence Our Attraction to Social Media?

MedicalResearch.com Interview with:

Chance York, Ph.D. Assistant Professor of Mass Communication Kent State University

Dr. Chance York

Chance York, Ph.D.
Assistant Professor of Mass Communication
Kent State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This research used twin study survey data from the Midlife in the United States (MIDUS) to investigate the relative influence of genetics and environment on social media use.

While the research cannot directly examine the gene-level influence on social media behavior, I was able to leverage known levels of genetic relatedness between identical and fraternal twins to suss out how much genetic traits and environmental factors impact frequency of using social media.

The results showed that between one- and two-thirds of variance in social media use is explained by genes, while environmental factors (parental socialization, peers, work, school, individual characteristics, etc.) explained the rest. In other words, this very specific communication behavior—social media use—is partially guided by our genetic makeup.

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GeneStrat Test Provides Quick Analysis of Genetic Lung Cancer Mutations

MedicalResearch.com Interview with:
Hestia Mellert, PhD

Director, Molecular Product Development
Biodesix: Making Medicine Personal
Boulder, CO

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies.

This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians.

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Proove Opioid Risk Profile Predictive of Opioid Use Disorder

MedicalResearch.com Interview with:

Maneesh Sharma, M.D</strong> Director of Pain Medicine MedStar Good Samaritan Hospital Medical Director of the Interventional Pain Institute Baltimore, Maryland

Dr. Maneesh Sharma

Maneesh Sharma, M.D
Director of Pain Medicine
MedStar Good Samaritan Hospital
Medical Director of the Interventional Pain Institute
Baltimore, Maryland

MedicalResearch.com: What is the background for this study?

Response: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Just in the last year alone according to the CDC, synthetic opioid deaths have increased 72%. As a practicing interventional pain specialist, I am confronted with the challenge of assessing patient risk for opioids as I evaluate multi-modal approaches to effective pain management. Existing tools are inadequate, as they either rely on a urine toxicology test to evaluate a patient’s current potential substance abuse as a predictor of future abuse, or on a patient’s honesty to fill out a questionnaire. We know that many patients who are not currently abusing illicit drugs or misusing prescription medications can develop prescription opioid tolerance, dependence, or abuse—especially with prolonged opioid therapy. Furthermore, we know that patients who are looking to abuse medications or divert those prescriptions will obviously lie on questionnaires.
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Trunk and Branch Drivers Distinguish Early vs Late Mutations in Hepatocellular Carcinoma

MedicalResearch.com Interview with:
Sara Torrecilla Recio

PhD Student
Mount Sinai Liver Cancer Program – Division of Liver Diseases Icahn School of Medicine at Mount Sinai
New York, NY

MedicalResearch.com: What is the background for this study?

Response: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which represents the second-leading cause of cancer related death worldwide. The landscape of molecular alterations in HCC has been thoroughly explored using next-generation sequencing technologies in single biopsies of tumors. However, in the recent years it has been demonstrated that not all the regions of a tumor harbor the same molecular alterations. This intra-tumor heterogeneity may lead to a misinterpretation of the molecular landscape of the malignancy since not all the molecular alterations would be captured by single-biopsies.

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Gene Linked To X-linked Intellectual Disability Identified In Less Than A Day

MedicalResearch.com Interview with:
Daryl Armstrong Scott, M.D., Ph.D
Associate Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This case started with a male child with intellectual disability, developmental delay, hypotonia, hypermobile joints and relative macrocephaly (large head size). Clinical testing showed that he carried a small deletion on chromosome Xp11.22. Since the deleted region had not been previously associated with human disease, the patient was referred to our clinic for additional testing. However, a more detailed analysis revealed that mice that were missing one of the genes located in the deletion interval, Maged1, had neurocognitive and neurobehavioral problems. This sparked additional inquiries which resulted in the identification of three other males from two other families who carried small, overlapping Xp11.22 deletions and had similar features. In all cases, their deletions were inherited from their asymptomatic mothers.

We concluded that deletion of an ~430 kb region on chromosome Xp11.22 that encompasses two pseudogenes (CENPVL1 and CENPVL2) and two protein-coding genes (MAGED1 and GSPT2) causes a novel, syndromic form of X-linked intellectual disability characterized by developmental delay, hypotonia, hypermobile joints and relative macrocephaly.

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New Breast Cancer Genes May Identify Women Who Can Benefit From Enhanced Screening

MedicalResearch.com Interview with:

Fergus J. Couch, Ph.D. Zbigniew and Anna M. Scheller Professor of Medical Research Chair, Division of Experimental Pathology Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, MN 55905

Dr. Couch

Fergus J. Couch, Ph.D.
Zbigniew and Anna M. Scheller Professor  of Medical Research
Chair, Division of Experimental Pathology
Department of Laboratory Medicine  and Pathology
Mayo Clinic
Rochester, MN

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The main finding is that RAD51D, BARD1, and MSH6 can now be included in the list of moderate risk breast cancer genes. In contrast, other genes such as MRE11A and RAD50 do not increase risk of breast cancer. In addition, we provide initial estimates of the level of breast cancer risk associated with mutations in the genes that cause breast cancer. The “new” breast cancer genes may now be useful for identifying women who can benefit from enhanced screening. These new data will need to be considered by the National Comprehensive Cancer Network (NCCN) which provides guidelines for clinical management of individuals with mutations in cancer predisposition genes. These results will also be useful for identifying members of families who are at increased risk of breast cancer.

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Gene Involved in Defective Skin Barrier and Eczema and Ichthyosis Identified

MedicalResearch.com Interview with:

Akio Kihara, PhD. Laboratory of Biochemistry Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan

Dr. Akio Kihara

Akio Kihara, PhD.
Laboratory of Biochemistry
Faculty of Pharmaceutical Sciences, Hokkaido University
Sapporo, Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The skin barrier is the most powerful defensive mechanism terrestrial animals possess against pathogens and harmful substances such as allergens and pollutants. Recent studies indicate that lipids play a central role in skin barrier formation. Multi-lamellar structures consisting of lipids are formed extracellularly in the stratum corneum, the outermost layer of epidermis, and their high hydrophobicity prevents the invasion of external pathogens and compounds.

The stratum corneum-specific lipid acylceramide is especially important for skin barrier formation. Decreases in acylceramide levels are associated with cutaneous disorders such as ichthyosis and atopic dermatitis. However, the mechanism behind acylceramide production is poorly understood, especially regarding the last step of acylceramide production: i.e., esterification of ω-hydroxyceramide with linoleic acid. This means that the broader picture of the molecular mechanisms behind skin barrier formation still remained unclear.

Although PNPLA1 has been identified as an ichthyosis-causative gene, its function in skin barrier formation remains unresolved. In the present study, we revealed that PNPLA1 catalyzes the last step of acylceramide synthesis. Our finding completes our knowledge of the entire pathway of the acylceramide production, providing important insights into the molecular mechanisms of skin barrier formation.

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26 Additional Genes Linked to Intellectual Disability Identified

MedicalResearch.com Interview with:
Dr. Muhammad Ayub MBBS, MRCPsych, MSc., MD

Professor of Psychiatry Chair Division of Developmental Disabilities
Department of Psychiatry Queens
University Kingston
Kingston ON Canada

MedicalResearch.com: What is the background for this study? 

Response: Intellectual Disability affects about 1 percent of the population worldwide. Genetics play a major role in its etiology. Better understanding of the genetic causes is a necessary step in development of improved diagnosis and treatment. Recessive inheritance where the affected child inherits a defective copy of a gene from both the parents is an important genetic mechanism for prevalence of the disease in populations where within family marriages are common. These types of marital bonds are common in South Asia and Middle Eastern countries. The families where parents are related are an effective resource to study recessive forms of Intellectual Disability.

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Novel Viral Vector Allows Gene Transfer To Correct Hearing Loss

MedicalResearch.com Interview with:

Lukas Landegger MD Molecular Neurotology Laboratory (PI Konstantina Stankovic) Massachusetts Eye and Ear Infirmary

Dr. Landegger

Lukas Landegger MD
Molecular Neurotology Laboratory (PI Konstantina Stankovic)
Massachusetts Eye and Ear Infirmary

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Genetic hearing loss affects more than 125 million people worldwide and constitutes a major hurdle for language acquisition and child development in general. Technological advances over the last decades, such as cochlear implants, have made it possible for deaf children to partially regain their sense of hearing. However, these devices still have several shortcomings, especially when listeners attempt to understand speech in noise or listen to music.

In establishing Anc80L65 as a reliable vector for gene delivery in the inner ear and releasing the first data demonstrating convincing hearing and vestibular function rescue in mice, we provide a foundation for other researchers interested in assessing the benefits of gene therapy in animal models of human disease.

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Rare Gene Variant Linked To Depressive Symptoms

MedicalResearch.com Interview with:
Najaf Amin, PhD
Erasmus University Medical Center
Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identifying genetic risk factors for depression has not been easy. Over a decade of genetic research did not yield a single replicable genetic factor for depression. It was only recently that 15 common genetic variants mostly in the non-coding parts of the genome were identified through a large genome-wide association study performed by 23andMe. All of these variants add a very small risk to depression individually (odds ratio < 1.05). These common variants cannot explain the cases that have a family history of depression.

Our hypothesis is that such familial cases are enriched for variants that are rare, lie in the coding region of the genome and thus have a large effect on depression. Such variants are enriched in families and isolated populations and therefore have a higher chance of being discovered compared to more cosmopolitan populations. Through gene-based analysis of rare coding variants we have identified a novel gene NKPD1 that may be relevant for depression. Further, we have noticed that the more deleterious the effect of the variant is on the protein, the larger the effect is on depressive symptoms.

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Colorectal Cancer Risk Model Using Environmental and Genetic Factors

MedicalResearch.com Interview with:

Victor Moreno, PhD. Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain Department of Clinical Sciences, Faculty of Medicine University of Barcelona Barcelona, Spain

Dr. Moreno

Victor Moreno, PhD.
Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
Department of Clinical Sciences, Faculty of Medicine
University of Barcelona
Barcelona, Spain

Gemma Ibáñez-Sanz, MD Gastroenterologist. *Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN *Gastroenterology Department, Bellvitge University Hospital-IDIBELL,  L’Hospitalet de Llobregat, Spain

Dr. Ibáñez-Sanz

Gemma Ibáñez-Sanz, MD
Gastroenterologist.
*Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN
*Gastroenterology Department, Bellvitge University Hospital-IDIBELL,
L’Hospitalet de Llobregat, Spain 

MedicalResearch.com: What is the background for this study?

Response: Colorectal cancer (CRC) screening by faecal occult blood testing has been demonstrated to reduce CRC incidence and mortality, as well as being a cost-effective strategy compared to no screening. Currently, the target population is defined basically by age (≥50 years old), which has been called a ‘one-size-fits-all’ strategy. This strategy implies performing unnecessary screening tests in low-risk people leading to avoidable risks for patients and extra costs for the healthcare system. On the other hand, high-risk patients may receive non-invasive testing, which is a suboptimal screening technique in their case. Several risk prediction models, either for  colorectal cancer or advanced neoplasia, have been previously developed, all with limited discriminating ability.

We have developed a risk stratification model that combines environmental factors with family history and genetic susceptibility. Furthermore, we have assessed the relative contribution of these factors and the utility of the model for risk stratification and public health intervention.

MedicalResearch.com: What are the main findings?

Response: Data from common genetic susceptibility loci could be useful to stratify colorectal cancer screening in average-risk population. Individuals in the top quintile of risk alleles have an 82% increased risk compared to those in the lower quintile. We have estimated the impact of determining an individual environmental and genetic risk score in a Spanish CRC screening population. In our model, although the genetic factors are significant contributors, the modifiable risk factors contribute more strongly. Risk assessment may increase screening participation and adoption of healthier lifestyles.

MedicalResearch.com: What should readers take away from your report?

Response: On average, each environmental risk factor increases CRC risk by 35%, while each risk allele only increases it by 7%. This implies that the change of one modifiable risk factor towards healthier lifestyle might offset the effect of 4 risk alleles. Given the fact that environmental factors explain part of the CRC risk, we believe it to be important to give thought to incorporating clinical data to encourage individuals to achieve a healthier lifestyle. As the European Code Against Cancer recommends, and our findings confirm, one should have a healthy diet, a healthy body weight, be physically active and should not smoke or a high consumption of alcohol.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Future prospective studies should aim to analyse if stratifying by genetic and lifestyle risk scores is useful and cost-effective to improve screening. Subjects with higher predicted risk should probably start screening earlier and decrease the intervals between tests, while low risk individuals could start later or space more the between test intervals.

MedicalResearch.com: Is there anything else you would like to add? 

Response: Population acceptability of genetic tests is not well known. We are currently recruiting subjects from colorectal cancer screening and gastroenterology clinics in a study called COLSCREEN to assess risk perception and attitudes regarding genetic testing to prevent cancer.

No disclosures

Citation:

Sci Rep. 2017 Feb 24;7:43263. doi: 10.1038/srep43263.

Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study.

Ibáñez-Sanz G1, Díez-Villanueva A1, Alonso MH1,2, Rodríguez-Moranta F2,3, Pérez-Gómez B2,4,5, Bustamante M2,6, Martin V2,7, Llorca J2,8, Amiano P2,9, Ardanaz E2,10, Tardón A2,11, Jiménez-Moleón JJ2,12, Peiró R2,13, Alguacil J2,14, Navarro C2,15, Guinó E1,2, Binefa G1,2, Navarro PF2,4,5, Espinosa A2,6, Dávila-Batista V7, Molina AJ2,7, Palazuelos C8, Castaño-Vinyals G2,6,16,17, Aragonés N2,4,5, Kogevinas M2,6,16,17,18, Pollán M2,4,5, Moreno V1,2,19.

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