Author Interviews, Genetic Research, Leukemia, Personalized Medicine / 12.11.2024

MedicalResearch.com Interview with: Professor Ong Sin Tiong Cancer & Stem Cell Biology Signature Research Programme Duke-NUS Medical School, Singapore Dr Yu Mengge Research Fellow, Cancer & Stem Cell Biology Signature Research Programme Duke-NUS Medical School MedicalResearch.com: What is the background for this study? Response: The background of this study is rooted in the observation that certain genetic variations among East Asian populations, notably the BIM deletion polymorphism (BDP), impact treatment outcomes in chronic myeloid leukaemia (CML). Patients with the BDP show resistance to conventional treatments, specifically tyrosine kinase inhibitors like imatinib. This resistance stems from the variant's role in promoting cancer cell survival, which leads to more aggressive disease progression. (more…)
AI and HealthCare, Author Interviews, Breast Cancer, Genetic Research / 06.11.2024

MedicalResearch.com Interview with: Prof. Dina Schneidman-Duhovny PhD Academic researcher Hebrew University of Jerusalem MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study analyzed genetic data of 12 families (~ 40 patients) with high incidence of breast cancer cases. Most families originate from ethnic groups that are poorly represented in public resources. All participants were tested negative to all known breast cancer predisposing genes. We developed a novel approach to study genetic variants utilizing state-of-the-art deep learning models tailored for analysis of familial data. The study highlighted 80 high-risk genes (out of > 1200 genes) and narrowed down on a group of 8 genes circulating in 7 out of 12 families in the study. These genes are involved in a cellular organelle called the peroxisome and play a role in fatty acids metabolism. We show that  these genes significantly affect breast cancer survival and use 3-dimensional protein structural analysis to illustrate the effect of some of the variants on protein structure. These provide strong evidence of the peroxisome involvement in breast cancer predisposition and pathogenicity, and provide potential targets for patient screening and targeted therapies. (more…)
Genetic Research / 16.10.2024

In medical school, students learn the significant facts about rare diseases, including their prognosis, treatment options, and predisposing factors. However, it's entirely different when a doctors diagnoses a patient with a rare disease and have to care for them. Since the providers wants to get all the details and provide the best care possible despite the limited information available, the task can prove challenging. This article shows steps to help ensure that patients get the quality of care they need. Consider Investigational Therapies Since there are not many drugs out there proven to be effective for treating rare diseases, investigational therapies might be worth trying for your patient.  Such treatments are worth considering when patients are experiencing severe side effects from using the conventional therapies and when the early study results of the investigational drugs are promising. Before proceeding with it  consider what the investigational drug is being studied for, the accessibility to clinical trial sites, and how much is already known about such therapies. For your patient's safety  the potential risks and the scientific evidence available must be examined and existing treatments exhausted. Determine if the patient will meet the inclusion criteria for participation in the study, such as the type or stage of their disease, age group, medical history, and current health status. As the physician, it is the responsibility to request such drugs. However, expanded access programs for investigational drugs are sometimes hard to navigate. If there is  difficulty getting patients into such clinical trials, you might want to consider using an Early Access Care program. Such programs connect patients to needed investigational products and streamline the request processes. (more…)
Author Interviews, Genetic Research, Nutrition, Pediatrics / 25.09.2024

MedicalResearch.com Interview with: Dr Zeynep Nas Ph.D. Postdoctoral Research Fellow Department of Behavioural Science and Health Institute of Epidemiology & Health Care University College London MedicalResearch.com: What is the background for this study? Response: We were interested in why some children are more selective in their food intake and more reluctant to try new foods compared to those who are not. We investigated this question in a twin study, which compares identical twins (who share all of their genes) to non-identical twins (who share half) to understand the relative influence of genetics versus the environment in shaping individual differences in fussy eating. (more…)
Author Interviews, Autism, Brigham & Women's - Harvard, Genetic Research / 26.08.2024

MedicalResearch.com Interview with: Caroline Dias, M.D., Ph.D. Assistant Professor, Pediatrics-Developmental Pediatrics University of Colorado Anschutz Medical Campus       Christopher Walsh, M.D., Ph.D. Chief, Division of Genetics and Genomics Bullard Professor of Pediatrics and Neurology at Harvard Medical School and researcher who has used material donated to the brain bank     MedicalResearch.com: What is the background for this study? Response: Many different types of genetic variants contribute to neurodevelopmental disorders such as autism. Copy number variants are large pieces of genetic material that are duplicated or deleted. We have known for many years that many copy number variants at certain genetic locations are linked to autism. Because these copy number variants may include lots of different genes, it has been difficult to understand how these copy number variants alter human brain function. Furthermore, although animal models are important, autism is in many ways defined by differences in uniquely human cognitive and social functioning. Better understanding of how these copy number variants change human brain function will shed light on universal mechanisms that regulate neurodevelopment. We studied a copy number variant called dup15q, that is associated with almost 40-fold higher rates of autism vs. the general population. We studied post-mortem human brain tissue from individuals with dup15q, individuals with autism not related to dup15q, and neurotypical controls, to better understand how the human brain is impacted by dup15q. We focused on frontal cortex, an important brain region in executive function and social perspective taking. We applied cutting edge techniques that allow us to assess individual cells in the brain.  (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, JAMA, Karolinski Institute, Prostate Cancer / 05.07.2024

MedicalResearch.com Interview with: Anna Plym PhD Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Epidemiology, Harvard T. H. Chan School of Public Health Department of Urology, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts MedicalResearch.com: What is the background for this study? Response: Prostate cancer is one of the leading causes of cancer death among men, with approximately one third of the deaths occurring before the age of 75 years. There is a need for a better understanding of the risk factors for those early deaths. Our previous research has indicated that inherited factors play a major role. (more…)
Author Interviews, Breast Cancer, Colon Cancer, Genetic Research, JAMA / 20.06.2024

MedicalResearch.com Interview with: Dr. Jeremy L. Davis M.D. Surgical Oncologist Center for Cancer Research Dr. Davis’ research focuses on sporadic and inherited forms of stomach cancer. National Cancer Institute   MedicalResearch.com: What is the background for this study? Response: Individuals who are born with a CDH1 gene mutation are at increased risk of developing specific cancers in their lifetime. Those cancers are called diffuse-type gastric cancer and lobular breast cancer. The background that is relevant here is that when mutations in this gene were first identified as the cause of inherited forms of these cancers, the estimated lifetime risk of gastric cancer, for instance, was around 60-83%. Because of this very high risk and because gastric cancer is particularly difficult to treat, many experts recommend prophylactic surgery to remove the stomach. In recent years, as we have seen more families who carry a CDH1 gene mutation, we have also observed that gastric cancer rates did not seem quite as high as those risk estimates would have suggested. We sought to re-evaluate lifetime risk of cancer with a large and diverse cohort of individuals throughout North America. (more…)
Author Interviews, Genetic Research, Heart Disease, Nature / 14.06.2024

MedicalResearch.com Interview with: Ben Omega Petrazzini, B.Sc. Associate Bioinformatician Ron Do Laboratory Ron Do, Ph.D. Professor, Department of Genetics and Genomic Sciences Director, Center for Genomic Data Analytics Associate Director in Academic Affairs, The Charles Bronfman Institute for Personalized Medicine Charles Bronfman Professor in Personalized Medicine Icahn School of Medicine at Mount Sinai     MedicalResearch.com: What is the background for this study? Response: Rare coding variants directly affect protein function and can inform the role of a gene in disease. Discovery of rare coding variant associations for coronary artery disease (CAD) to date have only had limited success. Genetic studies typically use standard phenotyping approaches to classify cases versus controls for CAD. However, this phenotyping approach doesn’t capture disease progression or severity in individuals. We recently introduced an in-silico score for CAD (ISCAD) that tracks CAD progression, severity, underdiagnosis and mortality (Forrest et al. The Lancet, 2023, PMID 36563696). ISCAD was built using a machine learning model trained on clinical data from electronic health records (EHR). Importantly, ISCAD is a quantitative score that measures CAD on a spectrum. The quantitative nature of the score provides an opportunity to discover additional rare coding variant associations that may not have been detected with the standard case-control phenotyping approach. Here in this study, we performed a large-scale rare variant association study in the exome sequences of 604,915 individuals for ISCAD, a machine learning-based score for CAD. (more…)
ASCO, Author Interviews, Breast Cancer, Genetic Research / 05.06.2024

MedicalResearch.com Interview with: Rima Patel, MD Assistant Professor, Division of Hematology/Oncology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai   MedicalResearch.com: What is the background for this study? Response: The 21-gene Oncotype DX Recurrence Score (RS) and 70-gene MammaPrint (MP) assays provide prognostic information for distant recurrence and are used to guide chemotherapy use in hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC). Previous reports have demonstrated racial differences in the prognostic accuracy of the RS. In both the TAILORx and RxPONDER trials, Black women with low genomic risk (RS 0-25) had a higher recurrence risk than White women. In another study using the NCDB database, Black race was associated with worse overall survival in multivariate models including RS. The impacts of race/ethnicity on the MammaPrint assay are unknown. (more…)
Endocrinology, Exercise - Fitness, Genetic Research / 21.05.2024

As public interest in health and wellness continues to grow, so does the number of innovative trends aimed at improving physical, mental, and emotional well-being. These new trends offer accessible and effective ways to enhance lifestyle choices and promote overall health. Individuals need to stay informed about these developments to make educated decisions that align with their health goals. By embracing novel and scientifically backed wellness practices, people can significantly enhance their quality of life, finding balance and improved health through modern solutions.

1.   Digital Fitness Apps

Digital fitness apps have redefined the way people engage with personal fitness, providing tools that help users manage their health and wellness directly from their smartphones. These apps offer a range of functionalities, including personalized workout plans, step tracking, calorie counting, and even virtual coaching sessions. The integration of these features makes it easier for users to stay committed to their fitness goals, providing a convenient and adaptable approach to exercise that fits into the user's lifestyle. The benefits of digital fitness apps extend beyond simple workout assistance; they also play a crucial role in motivating users to stay active and healthy. By setting personalized goals and receiving instant feedback on progress, users can see tangible results that encourage continued effort. Additionally, many apps now offer social connectivity features, allowing users to join communities of like-minded individuals who support and inspire each other. This sense of community can be particularly motivating, making it easier for individuals to maintain a consistent fitness routine. (more…)
Diabetes, Genetic Research / 16.05.2024

How At-Home Genetic Testing Can Detect Your Diabetes Risk 

Disclaimer: This blog content is for informational purposes only and should not be taken as medical advice. In recent years, the popularity of at-home genetic testing has surged, offering individuals ease and convenience at their doorstep. These tests provide a glimpse into their genetic blueprint and the potential health risks they might face. The promise of insights into various genetic predispositions, including the risk for diseases like diabetes is one you can’t miss.  While these tests can provide valuable information about one's genetic susceptibility to diabetes, it is crucial to approach the results with caution. They are not a substitute for traditional methods of diabetes screening and risk assessment but can complement them by providing additional layers of insight. (more…)
Author Interviews, Dermatology, Genetic Research, Nature, Rheumatology / 28.03.2024

MedicalResearch.com Interview with: Chelisa Cardinez PhD Postdoctoral Researcher The Burr Laboratory- Cancer Immunology and Epigenetics Genome Sciences and Cancer Division The John Curtin School of Medical Research The Australian National University Canberra, Australia   MedicalResearch.com: What is the background for this study? Response: Psoriasis is a skin inflammatory disease that affects approximately 2-3% of the population. Previous research had identified that the cytokine IL-17 drives the development of this disease. However, key questions that remained unknown about psoriasis included where did the IL-17 come from, and why do some patients with psoriasis also go on to develop systemic inflammatory conditions such as arthritis. Our research aimed to address these questions using a gain of function (GoF) mouse model that carried a genetic variant in a gene called IKBKB. (more…)
Author Interviews, Genetic Research / 31.01.2024

The market for personal genetic-testing kits is experiencing significant growth, enabling individuals to explore their ancestry and health vulnerabilities for a few hundred dollars. Genetic testing, or DNA test, is a medical examination designed to detect mutations in genes, chromosomes, or proteins. These mutations serve as indicators for the presence or absence of genetic conditions. Moreover, DNA tests can reveal your susceptibility to particular health conditions or the likelihood of passing on a genetic disorder. Before you go to DNA testing in Gainesville, GA, know everything in detail. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Hearing Loss, Lancet, Pediatrics / 29.01.2024

MedicalResearch.com Interview with: Zheng-Yi Chen, D.Phil. Department of Otolaryngology-Head and Neck Surger Harvard Medical School Boston, MA MedicalResearch.com: What is the background for this study?  Would you briefly explain the process and indication Response: This clinical trial is to use gene therapy to treat a type of genetic hearing loss. Genetic hearing loss mainly affects children. One in 600 newborns can have genetic hearing loss. There is no drug treatment for any type of hearing loss except for cochlear implants, which have limitations. This study focuses on a type of genetic hearing loss, DFNB9, due to a missing gene called Otoferlin. Without Otoferlin,  children are born with complete hearing loss and without the capacity to speak. The goal of the trial is to study if gene therapy is safe and efficacious in treating children so they can regain hearing and the ability to speak. (more…)
Abuse and Neglect, Author Interviews, Gender Differences, Genetic Research, Science, University of Michigan / 05.01.2024

MedicalResearch.com Interview with: Jianzhi "George" ZhangMarshall W. Nirenberg Collegiate ProfessorDepartment of Ecology and Evolutionary BiologyUniversity of MichiganAnn Arbor, MI 48109-1085 MedicalResearch.com: What is the background for this study? Response: A few percent of humans perform same-sex sexual behavior (SSB), a trait that is partially heritable. Because SSB leads to fewer children, the stable maintenance of SSB-associated alleles in populations has been a long-standing Darwinian paradox. A number of hypotheses have been proposed to resolve this paradox, but most of them lack clear empirical evidence. One version of the antagonistic pleiotropy hypothesis posits that SSB-associated alleles are subject to heterosexual advantage. Specifically, it was found that SSB-associated alleles are associated with more sexual partners when in heterosexuals (individuals of exclusive opposite-sex sexual behavior), which could lead to more offspring, potentially compensating the reduced reproduction of SSB individuals. While the above mechanism has likely worked in premodern societies, our recent study (PNAS 2023) found that it is no longer working in the modern United Kingdom, because the widespread use of contraception has decoupled the number of offspring from the number of sexual partners in heterosexuals. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, JAMA, Stanford / 07.11.2023

MedicalResearch.com Interview with: Michael E. Belloy, PhD Department of Neurology and Neurological Sciences Stanford University, Stanford, California MedicalResearch.com: What is the background for this study? Response: Apolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, genetic variants for late-onset Alzheimer disease. As such, one’s APOE genotype is highly relevant towards clinical trial design and Alzheimer’s disease research. However, most insights so far are focused on the associations of these APOE genotypes with Alzheimer’s disease risk in non-Hispanic white individuals. One important aspect of our work is that we really increased sample sizes for non-Hispanic Black, Hispanic, and East Asian individuals, so that we now have better understanding of the associations of APOE genotypes with Alzheimer’s disease risk in these groups. In complement, we also did the largest investigation to date on the role of ancestry on the associations of APOE genotypes with Alzheimer’s disease risk. The scale of our study was thus a critical factor in generating novel insights. (more…)
Author Interviews, Genetic Research, Melanoma / 06.10.2023

MedicalResearch.com Interview with: Dr Mitchell Stark B.App.Sc (Hons), PhD UQ Amplify Senior Research Fellow Skin Cancer Genomics and Biomarker Discovery Group Leader Frazer Institute Faculty of Medicine The University of Queensland Translational Research Institute Woolloongabba, QLD 4102   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nodular melanoma (NM) is one of the most aggressive subtypes of melanoma. Despite making up only 14 per cent of cases, it is the largest contributor to melanoma deaths. Nodular melanoma is difficult to catch early because it grows fast and has often spread deeper in the skin by the time it’s diagnosed. Around a quarter of NM cases also appear as a skin-coloured tumour, which might go unnoticed for longer. In this study we wanted to determine whether there were genetic variants associated with nodular melanoma, which might contribute to nodular melanoma risk. We identified 39 genes with rare DNA variants which had the greatest frequency in nodular melanoma patients compared to non-NM patients. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Ovarian Cancer / 07.08.2023

MedicalResearch.com Interview with: Pei Wang, PhD Professor, Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Michael J. Birrer MD PhD Director, Winthrop P. Rockefeller Cancer Institute University of Arkansas for Medical Sciences Little Rock, AR 72205 Amanda G. Paulovich MD PhD Translational Science and Therapeutics Division Fred Hutchinson Cancer Center Seattle WA 98109 MedicalResearch.com: What is the background for this study? How common is serous ovarian cancer? Response: Epithelial ovarian cancer accounts for >185,000 deaths/year worldwide. The most common subtype, high-grade serous ovarian cancer (HGSOC), accounts for 60% of deaths. Despite improvements in surgical and chemotherapeutic approaches, HGSOC mortality has not changed in decades. Five-year survival remains ~30% for the majority of patients. Standard of care involves surgical debulking combined with adjuvant or neoadjuvant chemotherapy with carbo- or cisplatin in combination with a taxane. At diagnosis, HGSOC is among the most chemo-sensitive of all epithelial malignancies, with initial response rates of ~85%, presumably related to DNA repair defects. Platinum is thought primarily to drive the response rate, due to the lower single-agent response rate for taxanes. Unfortunately, 10-20% of HGSOC patients have treatment-refractory disease at diagnosis, fail to respond to initial chemotherapy, and have a dismal prognosis. The poor response to subsequent therapy and median overall survival of ~12 months for these patients has not changed in 40 years. Despite >30 years of literature studying platinum resistance in cancer, there currently is no way to distinguish refractory from sensitive HGSOCs prior to therapy. Consequently, patients with refractory disease experience the toxicity of platinum-based chemotherapy without benefit. Due to their rapid progression, they are commonly excluded from participating in clinical trials. Consequently, there is no ongoing clinical research that could identify effective therapeutic agents for these patients or provide insights into molecular mechanisms of refractory disease.  “Right now, we can’t identify drug-resistant ovarian cancer patients up front,” said co-senior author Michael Birrer, MD, PhD, who directs UAMS’ Winthrop J. Rockefeller Cancer Institute. “We find them by default: They get sick and pass away so quickly that they can’t even be put on new clinical trials.” To address this unmet clinical need, we performed proteogenomic analysis of treatment-naïve HGSOCs (chemo-sensitive and chemo-refractory) to identify molecular signatures of refractory HGSOC and to identify potential treatment targets. (more…)
Author Interviews, Genetic Research, JAMA, Pediatrics / 17.07.2023

MedicalResearch.com Interview with: Prof. Jonathan Davis, MD, Chief of Newborn Medicine Tufts Medical Center and   Jill Maron, MD, MPH Chief of Pediatrics Women & Infants Hospital of Rhode Island   MedicalResearch.com: What is the background for this study? Response: The Genomic Medicine for Ill Neonates and Infants (GEMINI) trial was designed to be the first comparative study to explore the diagnostic yield, clinical utility and time to diagnosis between whole genomic sequencing (WGS) and a targeted genomic sequencing panel specifically designed to detect gene disorders that present in early life. GEMINI was a US based study that enrolled 400 hospitalized infants, along with their available parents, suspected of having an undiagnosed genetic diagnosis. Every participant underwent testing on each platform simultaneously, allowing us to better understand the limitations and advantages of each approach. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 14.06.2023

MedicalResearch.com Interview with: Alexandra M Whiteley PhD Department of Biochemistry University of Colorado Boulder Boulder, Colorado MedicalResearch.com: What is the background for this study? Response: My laboratory was interested in understanding how UBQLN2 maintains cellular health. Ubiquilins facilitate protein degradation, but the precise proteins that they help to break down were not well understood. UBQLN2 is of particular interest because mutations in the UBQLN2 gene lead to a familial form of ALS. This project, which was published in eLife this year, stems from work that was published when I was a postdoctoral researcher at Harvard Medical School, where we found a link between UBQLN2 and the virus-like protein PEG10. Now at the University of Colorado, Boulder, my laboratory has focused on trying to understand this connection between the two proteins, and how PEG10 could contribute to ALS. (more…)
ASCO, Author Interviews, Cancer Research, Genetic Research, JAMA, Race/Ethnic Diversity, Stanford / 06.06.2023

MedicalResearch.com Interview with: Allison W. Kurian, M.D., M.Sc. Professor of Medicine and of Epidemiology and Population Health Associate Chief, Division of Oncology Co-Leader, Population Sciences Program, Stanford Cancer Institute Director, Women’s Clinical Cancer Genetics Program Stanford University School of Medicine Stanford, CA 94305-5405 MedicalResearch.com: What is the background for this study? What types of cancers were in the study? Response: Genetic testing for cancer risk is increasingly important after a cancer diagnosis, to inform use of targeted therapies, secondary cancer prevention approaches and cascade genetic testing of family members. However, very little is known about how genetic testing is used after a cancer diagnosis at the population level. We leveraged a very large population-based data resource, the Surveillance, Epidemiology and End Results (SEER) cancer registries of the states of California and Georgia, and linked data from these registries to clinical genetic testing results provided by the four major laboratories that provide such testing. We used this linked registry-genetic testing dataset to study adults (age >=20 years) diagnosed with all types of cancer in the states of Georgia and California from 2013-2019. (more…)
Author Interviews, Genetic Research, PNAS, UCSD / 20.04.2023

MedicalResearch.com Interview with: Chinmay Kalluraya a Selma and Robert Silagi Award for Undergraduate Excellence winner UC San Diego and now a graduate student at MIT and Matt Daugherty  Ph.D Associate Professor University of California, San Diego Department of Molecular Biology, School of Biological Sciences La Jolla CA, 92093-0377 MedicalResearch.com: What is the background for this study? Would you explain the role of retinoid-binding protein? eye, visionResponse: We were broadly interested in discovering instances of bacterial genes that have been acquired by diverse animal genomes over millions of years of evolution by the process of horizontal gene transfer (HGT). Since these events are quite rare and most previous discoveries have been serendipitous, we developed computational methods to identify genes acquired by HGT in animals. One of the exciting discoveries from our work was that vertebrate IRBP appeared to have originated in bacteria and is now a critical component of the vertebrate visual cycle, so this paper focuses on that one discovery. IRBP or interphotoreceptor retinoid binding protein is an important protein present in the space between two major cell types in our eyes, photoreceptor cells and RPE cells. Our ability to see involves an intricate set of steps where light is first sensed by causing a change (isomerization) in the chemical structure of molecules in the eye called retinoids. This sensing of light occurs in our photoreceptor cells. Following this change in the chemical structure, the retinoid needs to be recycled back to the chemical structure that can again sense light. This recycling occurs in RPE cells. IRBP performs the essential function of shuttling retinoids between the photoreceptors and the RPE cells, which allows the cycle of sensing and regeneration to work. Supporting its importance, mutations in IRBP (also known as retinol binding protein 3 or RBP3) can cause several severe human eye diseases. (more…)
Author Interviews, Genetic Research, Neurological Disorders, Novartis / 29.03.2023

MedicalResearch.com Interview with: Sitra Tauscher-Wisniewski, MD Vice President Clinical Development & Analytics Novartis Gene Therapies MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of Spinal muscular atrophy (SMA)? Response: At the 2023 Muscular Dystrophy Association Conference, we presented new data from two of our  Long-Term Follow-Up (LTFU) studies, LT001 and LT002, which show the continued efficacy and durability of Zolgensma across a range of patient populations, with an overall benefit-risk profile that remains favorable. LT001 is a 15-year ongoing observational LTFU study following the Phase 1 START patients, who were the very first patients to receive our gene replacement therapy. LT-002 is a voluntary Phase 4 15-year ongoing follow-up safety and efficacy study of Zolgensma IV and investigational intrathecal (IT) OAV101 in patients previously treated in the Phase 3 IV studies (STR1VE-US, STR1VE-EU, STR1VE-AP, SPR1NT) and the Phase 1 IT study (STRONG). Spinal muscular atrophy (SMA) is a rare, devastating genetic disease that leads to progressive muscle weakness, paralysis, and when left untreated in one of its most severe forms (SMA Type 1), permanent ventilation or death in 90% of cases by age 2. It is caused by a lack of a functional survival motor neuron 1 (SMN1) gene, and in the most severe forms results in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement. (more…)
Addiction, Author Interviews, Genetic Research, Nature / 29.03.2023

MedicalResearch.com Interview with: Alexander S. Hatoum, PhD Research Assistant Professor Institute for Behavioral Genetics Washington University in St. Louis     MedicalResearch.com: What is the background for this study? Response: It is well known that someone with one substance use disorder will have another sometime in their lifetime or concurrently.  Further, individuals that do manifest two or more substance use disorders in their lifetime have the most morbid conditions. However, research often ignores the comorbidity and focuses on diagnosis of one substance use disorder at a time (i.e. opioid use disorder or alcohol use disorder). We set out to identify the biology behind the cross-substance liability. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research / 27.03.2023

MedicalResearch.com Interview with: Florence Le Calvez-Kelm, Ph.D. Genomic Epidemiology Branch International Agency for Research on Cancer Lyon, France and Trevor Levin Ph.D. Founder and CEO of Convergent Genomics that produces the Uroamp assay San Francisco, CA     MedicalResearch.com: What is the background for this study? Response: Bladder cancer is one of the most expensive and challenging to diagnose and treat. Therefore, identifying cost-effective urine bladder cancer biomarkers to complement or replace the gold-standard invasive and costly cystoscopy for the early detection and monitoring of this highly recurrent disease is crucial. At the international Agency for research on Cancer (IARC-WHO), we have developed a simple urine-based assay TERT promoter mutations, the most common mutations in bladder cancer, and showed that the urine biomarker could detect bladder cancer patients at diagnosis but many years prior to clinical diagnosis. However, in this study, we wanted to see whether a more comprehensive genomic profiling of urine samples collected years prior to clinical diagnosis of bladder cancer could identify even more patients before they develop any symptoms. The study was based on the UroAmp test, a general urine test that identifies mutations in 60 genes, developed by the Oregon Health Science University spin out company, Convergent Genomics. Drawing on previous research to identify genetic mutations linked to bladder cancer, the research team narrowed the new test down to focus on mutations within just ten genes. Working with colleagues from the Tehran University of Medical Sciences in Iran, they trialled the potential new test using samples from the Golestan Cohort Study, which has tracked the health of more than 50,000 participants over ten years, all of whom provided urine samples at recruitment. Forty people within the study developed bladder cancer during that decade, and the team were able to test urine samples from twenty-nine of them, along with samples from 98 other similar participants as controls. (more…)
Author Interviews, Genetic Research / 21.03.2023

MedicalResearch.com Interview with: Ernest Turro, PhD Associate Professor Genetics and Genomics Sciences The Turro group runs a research program on statistical genomics, with a dual focus on rare diseases and blood-related traits at the Icahn School of Medicine Mount Sinai Health System   MedicalResearch.com: What is the background for this study? Would you describe the Rareservoir database? Response:   The main motivation for our work is that only half of the approximately 10,000 catalogued rare diseases have a resolved genetic cause (or aetiology). Patients with these diseases are unable to obtain a genetic diagnosis which could otherwise inform prognosis, treatment for themselves and affected relatives. One route towards resolving the remaining aetiologies is to enroll large numbers of rare disease patients into research studies so that statistical analyses can be performed comparing the genetic with the clinical characteristics of the study participants. One major endeavour, the 100,000 Genomes Project (100KGP), sequenced the genomes and collected clinical phenotype data for 34,523 UK patients and 43,016 unaffected relatives across 29,741 families. The scale of this study is unprecedented, partly thanks to the ever-decreasing cost of DNA sequencing (25 years ago, it cost $1bn to sequence a whole genome, while now it costs only a few hundred dollars). Working with such large datasets is notoriously cumbersome. To overcome this, we developed a computational approach (the Rareservoir) that distills the most important information into a relatively small database, allowing us to apply our statistical methods nimbly. We noted that the "genetic variants" that cause rare diseases are typically kept rare in the human population by natural selection because affected individuals tend to have few children, if any. This meant that we could discard the genetic information corresponding to variants that are common in the human population without throwing away the key disease-causing variants. By focussing on these "rare variants", we were able to perform our analyses using a small database (a `Rareservoir’), only 5.5GB in size, hastening our progress significantly. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA, Personalized Medicine, Vanderbilt / 18.03.2023

MedicalResearch.com Interview with: Jonathan Mosley, MD, PhD Associate Professor Division of Clinical Pharmacology Departments of Internal Medicine and Biomedical Informatics Vanderbilt University Medical Center MedicalResearch.com: What is the background for this study? Response: Prostate cancer is an important source of morbidity and mortality among men. Earlier detection of disease is essential to reduce these adverse outcomes. Prostate cancer is heritable, and many single nucleotide polymorphisms (SNPs) associated with disease risk have been identified. Thus, there is considerable interest in using tools such as polygenic risk scores, which measure the burden of genetic risk variants an individual carries, to identify men at elevated risk of disease. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Race/Ethnic Diversity, Stanford / 21.02.2023

MedicalResearch.com Interview with: Yann Le Guen, Ph.D. Assistant Director, Computational Biology Quantitative Sciences Unit Stanford Medicine MedicalResearch.com: What is the background for this study? Response: Apart from aging, the strongest contributing factor for late-onset Alzheimer’s disease is a specific allele of the APOE gene, which has three common alleles E2, E3, and E4. While E3 is the most common and considered as the reference, E2 is associated with decreased Alzheimer’s disease risk and E4 is associated with increased Alzheimer’s disease risk. Notably the prevalence of E4 among Alzheimer’s patient is high with about 60% of these carrying at least one E4 allele, while solely about 30% Americans carry one E4 allele. It’s worth emphasizing that individuals with an E4/E4 genotype have an exponential increased in their risk to develop AD (10 times as likely than the reference E3/E3 genotype), and individuals with an E3/E4 genotype have an intermediate risk. Though, most studies of Alzheimer’s disease genetic have been focused on European ancestry, this is beginning to change thanks to NIH’s efforts to fund more studies in non-European ancestry individuals. Our study built on these recent efforts to assess the Alzheimer disease risk associated with an APOE variant (R145C) present in about ~4% African Americans, but extremely rare in Europeans. (more…)
Author Interviews, Genetic Research, NIH, Pediatrics / 20.02.2023

MedicalResearch.com Interview with: Natalie Shaw, M.D., MMSc. Principal Investigator Head of the Pediatric Neuroendocrinology Group Dr. Shaw holds a secondary appointment in NIEHS Reproductive and Developmental Biology Laboratory.   MedicalResearch.com: What is the background for this study? Would you briefly describe the two affected conditions? Dr. Shaw: Congenital arhinia is a rare congenital malformation characterized by the complete absence of an external nose and internal olfactory (smell) structures.  It is frequently associated with eye and reproductive defects.  Facioscapulohumeral muscular dystrophy (FSHD) type 2 is a form of muscular dystrophy that presents in young adulthood.  Both conditions are caused by mutations in the gene SMCHD1.  In FSHD type 2, we know that loss of SMCHD1 activity leads to expression of a toxic protein called DUX4 in muscle.  The cause of arhinia was unknown. (more…)
Author Interviews, Coffee, Genetic Research, JAMA, Kidney Disease / 15.02.2023

MedicalResearch.com Interview with: Dr. Sara Mahdavi, PhD Clinical Scientist and Clinical Instructor Research Appointment in the Faculty of Medicine University of Toronto Toronto, ON MedicalResearch.com: What is the background for this study? Response: This was a long-term study spanning 16 years and began with a population of young adults who were medically assessed on a regular basis. It was remarkable to see just how striking the effects of coffee were in the group that had the susceptible genetic variant, what we termed “slow caffeine metabolizers” yet no effect whatsoever in those who did not were termed “fast metabolizers”. (more…)