Maybe Spinal Repair Cells Can Be Turned On and Off

MedicalResearch.com Interview with:

Pier Lorenzo Puri, M.D PhD Professor in the Development, Aging and Regeneration Program Sanford Burnham Prebys Medical Discovery Institute 

Dr. Puri

Pier Lorenzo Puri, M.D PhD
Professor in the Development, Aging and Regeneration Program
Sanford Burnham Prebys Medical Discovery Institute 

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

Response: My lab has been studying special repair cells called fibro-adipogenic progenitors (FAPs) and how these cells change in models of motor neuron diseases. These cells usually repair muscles after acute injury. But we are finding the FAPs change dramatically in disease settings.

In this study we looked at these cells in models of spinal cord injury, ALS and spinal muscular atrophy, including muscle tissue from ALS patients. We found that FAPs change radically in several ways.

Most importantly, the cells used a different signaling pathway, IL-6-STAT3, and when we blocked this signaling muscle atrophy and fibrosis halted. While further studies in humans are needed, this is a promising finding as FDA-approved medicines that block IL-6 and STAT3 are available.  Continue reading

Pregabalin Linked To Increased Risk for Opioid-Related Deaths

MedicalResearch.com Interview with:

Tara Gomes, MHSc Li Ka Shing Knowledge Institute, St Michael’s Hospital, The Institute for Clinical Evaluative Sciences Leslie Dan Faculty of Pharmacy Department of Health Policy, Management, and Evaluation University of Toronto, Toronto, Ontario, Canada

Tara Gomes

Tara Gomes, MHSc
Li Ka Shing Knowledge Institute, St Michael’s Hospital,
The Institute for Clinical Evaluative Sciences
Leslie Dan Faculty of Pharmacy
Department of Health Policy, Management, and Evaluation
University of Toronto, Toronto, Ontario, Canada 

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

Response: Pregabalin is a medication increasingly being prescribed to manage pain, however there is emerging evidence that this drug may increase one’s risk of opioid overdose when prescribed with opioids.

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How Our Brain Lets Us Believe What We Want To Believe

MedicalResearch.com Interview with:

People demonstrate biased belief updating: They tend to regard good news indicating that personal risks are lower than expected, and to disregard bad news indicating that personal risks are higher than expected. Kuzmanovic and colleagues show that this optimism bias depends on the update valuation by the ventromedial prefrontal cortex (vmPFC) and its influence on the dorsomedial prefrontal cortex (dmPFC) associated with self-referential reasoning. Credit: Bojana Kuzmanovic

People demonstrate biased belief updating: They tend to regard good news indicating that personal risks are lower than expected, and to disregard bad news indicating that personal risks are higher than expected. Kuzmanovic and colleagues show that this optimism bias depends on the update valuation by the ventromedial prefrontal cortex (vmPFC) and its influence on the dorsomedial prefrontal cortex (dmPFC) associated with self-referential reasoning.
Credit: Bojana Kuzmanovic

Dr. Bojana Kuzmanovic PhD
Max Planck Institute for Metabolism Research
Translational Neurocircuitry Group
Cologne, Germany

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

Response: Do our beliefs depend on what we want to believe? Until now, researchers failed to show how interactions between brain regions mediate the influence of motivation to adopt desirable notions on ongoing reasoning. Our study used optimized design and analyses to rule out alternative explanations and to identify underlying neurocircuitry mechanisms.

MedicalResearch.com: What are the main findings?

Response: First, we demonstrated that people’s belief formation behavior depends on their preferences. When people were asked to reconsider their beliefs about their future outcomes, they tended to rely more strongly on good news and to disregard bad news.

Second, we showed that favorable belief updating activated the brain valuation system known to be responsive to rewards such as food or money (ventromedial prefrontal cortex, vmPFC). That is, the valuation system was activated when participants incorporated good news to improve their risk estimates, and when they disregarded bad news to avoid a worsening of their risk estimates.

And third, the valuation system influenced other brain regions that are involved in deriving conclusions about oneself (dorsomedial prefrontal cortex, dmPFC). Importantly, the more participants were biased in their belief formation behavior, the stronger was the engagement and the influence of the valuation system.

The influence of the valuation system on the reasoning system helps to understand how motivation can affect reasoning. It supports the idea that memories and knowledge we recall to form our beliefs are selected in such a way as to yield the desired conclusions. For example, when we wish to convince ourselves that our risk of having a heart attack is low although federal statistics indicate a higher risk, we might recall our healthy life style but not our family history of heart-related diseases, or neglect the fact that the federal population may have a comparable life style. Continue reading

PITS Gene Linked To Rare Neurologic Disorders

MedicalResearch.com Interview with: 

Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030

Dr. Marcogliese

Paul C Marcogliese, Ph.D.
Postdoctoral Associate,
Laboratory of Dr. Hugo Bellen
Department of Molecular and Human Genetics
Baylor College of Medicine
Houston, Texas 77030

Loren D. Pena, MD PhD Pediatric Medical Genetics Specialist Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine, Durham, NC

Dr. Peña


Loren D. Pena, MD PhD
Division of Human Genetics
Cincinnati Children’s Hospital Medical Center
Department of Pediatrics
University of Cincinnati
Cincinnati, OH 45229


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

Response: The Undiagnosed Diseases Network (UDN) is a multi-site collaboration across the US that seeks to help diagnose patients with rare disorders that are ill-defined.

Dr. Loren D.M. Pena and Dr. Vandana Shashi at the Duke-Columbia clinical site of the UDN had seen a patient with a severe neurological disorder. While the patient had no symptoms at birth, the patient began falling at about 3 years of age, eventually losing motor coordination and developing seizures. In the interim, the regression has progressed to a severely debilitating state. Re-analysis of the participant’s exome data by our site bioinformatician at Columbia (Nicholas Stong) in Dr. David Goldstein’s laboratory revealed a truncating variant in the single exon gene IRF2BPL that could be the candidate disease-causing gene. The UDN clinicians at Duke then contacted the UDN Model Organism Screening Center (MOSC) led by Dr. Hugo Bellen at Baylor College of Medicine and the Howard Hughes Medical Institute for functional analysis. In parallel, four more patients were found with truncating mutations causing a similar disorder though the UDN and GeneMatcher.org. Additionally, two patients with missense variants in IRF2BPL were identified that displayed seizures and some developmental delay or autism spectrum disorder but no motor regression.

Work in MOSC by Dr. Paul Marcogliese using fruit flies revealed that the IRF2BPL truncating variants are severe loss of function mutations and one of the missense variants was a partial loss of function. Additionally, it was found that the fruit fly IRF2BPL gene, called pits, is expressed in the neurons of the adult fly brain. Lowering the levels of pits by about 50% in fly neurons leads to progressive behavioural abnormalities and neurodegeneration. By combining the human genetics, bioinformatics and model organism data, IRF2BPL was found to be a novel disease-causing gene in humans.

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Statins May Reduce Need For Surgery in Chronic Subdural Hematoma

MedicalResearch.com Interview with:
Jianning Zhang MD, Ph.D Chairman, II, VII Chinese Medical Association of Neurosurgery President, Tianjin Medical University General Hospital, China  Jianning Zhang MD, Ph.D
Chairman, II, VII Chinese Medical Association of Neurosurgery
President, Tianjin Medical University General Hospital,
China  

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

Response: The elderly population is growing dramatically world widely, especially in China. The incidence of chronic subdural hematoma has been rising over the past years. Although the surgery is not a difficult process, the risk of death and recurrence persist, and the affliction and economic expenditure of the patients are relatively higher in the elderly. For these reasons, it is urgent to develop novel pharmacological therapies with sufficient safety and efficacy. 

It has been known that the high expression of VEGF and inflammatory factors in chronic subdural hematoma can lead to abundant angiogenesis of immature vessels on the wall of hematoma. In our previous study, patients with chronic subdural hematoma have impaired ability to promote vascular maturation. For example, the number of endothelial progenitor cells in circulating blood is about 67% of the healthy individuals with similar age. 

Atorvastatin can mobilize endothelial progenitor cells to reduce inflammation. It increases the number of circulating endothelial cells that are inversely correlated with the volume of hematoma. We have demonstrated that atorvastatin can promote endothelial cell formation and reduce the leakage of endothelial cell barrier in vitro. Results from in vivo experiments in animal models of subdural hematoma suggest that atorvastatin can promote the maturation of blood vessels and reduce inflammation on the margin of hematoma, and thus improve the neurological outcome. Continue reading

Migraine Management Crucial For Treatment of Tinnitus

MedicalResearch.com Interview with:
“Day 50: Headache” by kizzzbeth is licensed under CC BY 2.0Jen-Tsung Lai, MD
Department of Otolaryngology
Kuang-Tien General Hospital
Shalu, Taichung, Taiwan

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

Response: Cochlear Migraine( CM ) is a new proposed diagnosis in 2018. CM could present as fluctuating hearing loss or sudden hearing loss that provoked the tinnitus.

Furthermore , CM with underlying hypersensitive brain might cause the tinnitus switch out of function.  

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

Response: Cochlear Migraine (could be one of the key code for chronic tinnitus. Similar to vestibular migraine (VM ) in vertigo diagnosis, Cochlear Migraine is a very important cause of tinnitus and heating loss.

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

Response: The clinical implication : the migraine management is crucial for tinnitus treatment. 

Citation:

Hwang J, Tsai S, Liu T, Chen Y, Lai J. Association of Tinnitus and Other Cochlear Disorders With a History of Migraines. JAMA Otolaryngol Head Neck Surg. Published online July 12, 2018. doi:10.1001/jamaoto.2018.0939

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How Quickly and Accurately Can Ischemic Stroke Be Diagnosed and Treated with tPA?

MedicalResearch.com Interview with:

Perttu J. Lindsberg, MD, PhD Professor of Neurology Clinical Neurosciences and Molecular Neurology Research Programs Unit, Biomedicum Helsinki University of Helsinki Helsinki, Finland

Dr. Lindsberg

Perttu JLindsberg, MD, PhD
Professor of Neurology
Clinical Neurosciences and Molecular Neurology
Research Programs Unit, Biomedicum Helsinki
University of Helsinki Helsinki, Finland

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

Response: The past 20 years in shaping the Helsinki model in stroke thrombolysis have proven that we can be very fast in examining the patient, completing the imaging and starting thrombolytic therapy. This is a university hospital center that receives roughly three stroke suspects per day for evaluation of recanalization therapies. Already seven years ago we were able to push the median ’door-to-needle’ time permanently below 20 minutes. What we had not been monitoring was how well we had kept up the accuracy of our emergengy department (ED) diagnostic process. Prehospital emergency medical services (EMS) have been trained to focus on suspecting thrombolysis-eligible stroke and we usually get also pre-notifications of arriving stroke code patients during transportation, but the diagnosis on admission is an independent clinical judgment as the CT findings are largely nondiagnostic for acute changes.

The admission evaluation of suspected acute stroke is therefore a decisive neurologic checkpoint, building the success of acute treatments such as recanalization therapy, but is complicated by differential diagnosis between true manifestations of stroke and numerous mimicking conditions. Although we have invested a lot on training and standardized ED procedures, time pressure and therapy-geared expectations may blur the diagnostic process.

With this background, we embarked on an in-depth-analysis of the admission and final diagnoses of stroke code patients, as well as misdiagnoses, immediate treatment decisions and their consequences.

Continue reading

Multimodal Imaging Can Personalize and Predict Therapeutic Needs

MedicalResearch.com Interview with:

Yasser Iturria-Medina, PhD Primary Investigator, Ludmer Centre for Neuroinformatics & Mental Health Assistant Professor, Department of Neurology and Neurosurgery Faculty of Medicine McGill University

Dr. turria-Medina

Yasser Iturria-Medina, PhD
Primary Investigator, Ludmer Centre for Neuroinformatics & Mental Health
Assistant Professor, Department of Neurology and Neurosurgery
Faculty of Medicine
McGill University

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

Response: There are millions of patients following therapeutic interventions that will not benefit them. In this study, we aimed to illustrate that it is possible to identify the most beneficial intervention for each patient, in correspondence with the principles of the personalized medicine (PM). Our results show that using multimodal imaging and computational models it is possible to predict individualized therapeutic needs. The predictions are in correspondence with the individual molecular properties, which validate our findings and the used computational techniques.

The results highly also the imprecision of the traditional clinical evaluations and categories for understanding the individual therapeutic needs, evidencing the positive impact that would have to use multimodal data and data-driven techniques in the clinic, in addition to the medical doctor’s criterion/evaluations.   Continue reading

Understanding the Neuroscience of Creativity Through Music Improvisation

MedicalResearch.com Interview with:

Andrew Goldman PhD Laboratory for Intelligent Imaging and Neural Computing Department of Biomedical Engineering, Columbia University Presidential Scholar in Society and Neuroscience, Columbia University Andrew Goldman PhD
Laboratory for Intelligent Imaging and Neural Computing
Department of Biomedical Engineering, Columbia University
Presidential Scholar in Society and Neuroscience,
Columbia University 

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

Response: Many Western musicians have difficulty improvising, despite having extensive training and experience. These musicians learn about and use similar musical structures in their playing (like chords, scales, rhythmic patterns, etc.) as experienced improvisers, but they may know about them in different ways. In other words, different musicians have different ways of knowing and learning about similar musical structures. To understand which ways of knowing facilitate the ability to improvise contributes to an understanding of how people are able to use knowledge creatively. Western music provides an important opportunity to compare these different ways of knowing because in other improvisatory domains of behavior (like speaking), it is difficult to find people who know how to do it but cannot improvise with it (e.g., if you know a language, you can very likely improvise with that language).

In order to advance our understanding of these improvisatory ways of knowing, we compared musicians with varying degrees of improvisation experience in a task that tested how they categorized musical chords. In Western music, different chords are theorized to have similar “functions.” For example, on a guitar, there are different ways to play a C chord, and you could often substitute one for the other. You might even play another chord in place of the C chord and have it sound similar, or lead to a similar subsequent harmony. Improvisers often use notation that specifies classes of chords rather than specific realizations (versions) of a chord whereas those who do not typically improvise use notation that specifies the full realization of the chord. By analogy, one chef might use a recipe that calls for “citrus” (in music, a class of musical chord) while another chef’s recipe might specifically call for “lemon” (in music, a specific realization of a functional class of chords). We tested whether improvisers categorize similar-functioning harmonies as more similar to each other than different-functioning harmonies, and compared how less experienced improvisers categorize the same harmonies.

Our task required the musicians to listen to a series of repeating harmonies (the “standard” stimuli) and pick out occasional chords that were different in any way (the “deviant” stimuli). Some deviant stimuli were different versions of the standard chord (like limes in place of lemons) and some deviant stimuli were chords with different musical functions (like bananas instead of lemons).

The more experienced improvisers were better at detecting the function deviants than the exemplar deviants whereas the less experienced improvisers showed little difference in their ability to detect the two types of deviants. In other words, because improvisers categorize the different versions of the same chord as similar, they have a relatively harder time picking out the similarly functioning harmonies. This was measured using behavioral data, and electroencephalography (EEG), which can be used to provide a neural measure of how different stimuli are perceived to be from each other.

Continue reading

Investigational RNAi Drug Patisiran Show Promise in Hereditary Amyloidosis

MedicalResearch.com Interview with:
Prof. David Adams Head of the French National Reference Centre for Familial Amyloidotic Polyneuropathy (NNERF)/APHP/INSERM Paris FranceProf. David Adams
Head of the French National Reference Centre for Familial Amyloidotic Polyneuropathy (NNERF)/APHP/INSERM
Paris France

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

Response: Hereditary transthyretin amyloidosis is an autosomal dominant, multisystemic, progressive, life-threatening disease caused by mutations in the gene encoding transthyretin (TTR ).

The liver is the primary source of circulating tetrameric TTR protein. In hereditary transthyretin amyloidosis, both mutant and wild-type transthyretin deposit as amyloid in peripheral nerves and the heart, kidney, resulting in polyneuropathy and cardiomyopathy. Neuropathic changes result in profound sensorimotor disturbances, with deterioration in activities of daily living and ambulation, hypotension, diarrhea, impotence, and bladder disturbances.

Until now,  only few patients have access to anti-amyloid therapy : Liver Transplantation or TTR stabilizers which are able only to slow progression of the disease at very early stage of the disease.

Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin and is specifically addressed to the liver by lipid nanoparticle (LNP) formulation.

This study carried out a multicenter, international, randomized, double-blind, placebo-controlled, phase 3 trial of patisiran in patients with hereditary transthyretin amyloidosis with polyneuropathy.

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CRISPR-Gold Has Potential To Edit Brain Genes

MedicalResearch.com Interview with:

Niren Murthy PhD Professor of Bioengineering University of California at Berkeley

Prof. Murthy

Niren Murthy PhD
Professor of Bioengineering
University of California at Berkeley

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

Response: In this paper we delivered Cas9 RNP in the brain using a delivery vehicle termed CRISPR-Gold.  We were able to knock out the mGluR5 gene and rescue mice from autism using CRISPR-Gold.  The background here is that there is a great need for safe and effective CRISPR delivery vehicles, and that brain gene editing has great therapeutic potential.  This paper demonstrates for the first time that non-viral delivery of Cas9 RNP into the brain can have therapeutic effects.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Brain gene editing has tremendous therapeutic potential, and can be achieved with non-viral Cas9 RNP delivery

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

Response:   We need to be able to edit the brains of large animals.  The particles will need to be modified for this, we are currently working on this.  GenEdit, a start-up company spun out from our lab, is also working on this.

Disclosures: I was a co-founder of GenEdit, but now have no equity in GenEdit, there should be no conflict of interest

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Bumwhee Lee, Kunwoo Lee, Shree Panda, Rodrigo Gonzales-Rojas, Anthony Chong, Vladislav Bugay, Hyo Min Park, Robert Brenner, Niren Murthy, Hye Young Lee. Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours. Nature Biomedical Engineering, 2018; DOI: 10.1038/s41551-018-0252-8

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

 

Eye Sign of Dementia Risk? Thinning of Retinal Nerve Fiber Layer

MedicalResearch.com Interview with:

Dr. Paul Foster

Dr. Foster

Paul Foster BMedSci(Hons) BMBS PhD FRCS(Ed) FRCOphth FRCS(Eng)
Professor of Glaucoma Studies & Ophthalmic Epidemiology
Research Theme Lead Integrative Epidemiology & Visual Function
UCL Institute of Ophthalmology & Moorfields Eye Hospital
London 

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

Response:  Dementia is the medical challenge of the moment – increasingly common, adversely impacting quality of life for millions, and a great worry for all. Efforts to identify treatments or interventions rely on being able to identify those people at greatest risk. Our motivation was to help identify those people, primarily to aid in the development of treatments through clinical trials.

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Which Brain Circuits Determine Maternal Behavior?

MedicalResearch.com Interview with:
“Mother and Child” by Mary Cassatt (American, Pittsburgh, Pennsylvania 1844–1926 Le Mesnil-Théribus, Oise) via The Metropolitan Museum of Art is licensed under CC0 1.0Yi-Ya Fang

NYU School of Medicine
Dayu Lin, PhD
Neuroscience Institute, New York University Langone School of Medicine,  Department of Psychiatry,
Center for Neural Science
New York, NY

Response: Maternal behaviors are essential for survival of offspring across mammalian species. In rodents, mothers show several characteristic pup caring behaviors including grooming pups, crouching over pups and approaching and retrieving pups. Decades of research has been trying to understand how the neural circuit is wired to generate these elaborate maternal behaviors. Medial preoptic area (MPOA), which is located at anterior part of hypothalamus, has been indicated to be important for maternal behaviors. Many studies consistently found deficits in maternal behaviors after damaging the MPOA. To dissect the maternal circuits in the brain, we looked into the properties of the Esr1+ cells.

In this study, we identify estrogen receptor α (Esr1) expressing cells in MPOA as key mediators of pup approach and retrieval. We focused on Esr1 (Esr1) expressing cells in the MPOA since estrogen has been shown to facilitate maternal behaviors, presumably through its action of estrogen sensing cells. We found that reversible inactivation of MPOA Esr1+ cells impairs maternal behaviors whereas optogenetic activation of MPOA Esr1+ cells induces immediate pup retrieval. Additionally, we found that MPOA Esr1+ cells are preferentially activated during maternal behaviors, and the cell responses changed across reproductive states. Tracing studies revealed that MPOA Esr1+ cells project strongly to ventral tegmental area (VTA), a region that has been indicated in motivation and reward. Specifically, MPOA Esr1+ cells provide strong inhibitory inputs preferentially to the GABAergic cells in the VTA, which in turn could disinhibit the dopaminergic cells.  VTA dopaminergic cells are highly activated during maternal behaviors.

Altogether, our study provides new insight into the neural circuit that generates maternal behaviors.

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Duchenne Muscular Dystrophy: As Survival Increases, New Focus on Quality of Life

MedicalResearch.com Interview with:
David Birnkrant, MD
Professor of Pediatrics, Case Western Reserve University School of Medicine
Director of Pediatric Pulmonology & Student Education, MetroHealth Medical Center

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

Response: This study updates guidance on all aspects of the multi-disciplinary care of patients with Duchenne muscular dystrophy (DMD). The project was funded by the CDC’s National Center on Birth Defects and Developmental Disabilities and the results were recently published as three articles in The Lancet Neurology. The project was guided by a 25-member steering committee. Eleven expert committees worked over a period of three years to develop guidelines based on the RAND/UCLA appropriateness method, in which assessments and interventions were evaluated for appropriateness and necessity. The recommendations update those originally published in 2010.

Duchenne muscular dystrophy is transmitted by X-linked recessive inheritance and thus affects primarily boys and men. Patients affected by DMD do not produce functional dystrophin protein, resulting in progressive weakness of skeletal, respiratory, and heart muscles, causing a shortened life span. Teens and young men may require surgery for curvature of the spine, a ventilator device to assist breathing, and a feeding tube to help ensure adequate nutrition. The approach of the various subspecialties involved in DMD management has evolved, with more anticipatory assessment and therapy, identifying and addressing predictable medical complications as early as possible for optimal patient outcomes. With this kind of multi-disciplinary care, people with DMD now live into their 30s and beyond.

Along with the emergence of new genetic and molecular therapies, the recognition that people with DMD are living longer was one of the main motivations behind the need for these updated care considerations. Patients with DMD, their families and their advocacy organizations are driving a new emphasis on optimizing quality of life, not just prolongation of survival. Thus, there was a need to address issues related to transitions of care from childhood to adulthood, coordination of care across subspecialties, and other topics related to education, vocation, independence, personal relationships, emotional health, and intimacy. The updated care considerations thus include eleven topic areas, eight of which were part of the 2010 guidelines.

These are: (1) diagnosis, (2) neuromuscular management, (3) rehabilitation management, (4) gastrointestinal and nutritional management, (5) respiratory management, (6) cardiac management, (7) orthopedic and surgical management, and (8) psychosocial management. Three topics are new: (9) primary care and emergency management, (10) endocrine management (including growth, puberty, adrenal insufficiency, and bone health), and (11) transitions of care across the lifespan.

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Early Clinical Trials of AMO-02 Show Promise in Congenital and Childhood Myotonic Dystrophy Type 1

MedicalResearch.com Interview with:

Joseph Horrigan MD, Pediatric neuropsychiatrist

Dr. Horrigan

Dr. Joseph Horrigan MD
Pediatric neuropsychiatrist

Chief medical officer

 


MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by myotonic dystrophy? What are the manifestations of this disease?

Response: This was the first pharmaceutical intervention study conducted in adolescents and adults with congenital and juvenile onset DM1. Myotonic dystrophy type 1 (DM1) is a disorder that impacts multiple body systems following a trinucleotide expansion repeat of the DMPK gene on chromosome 19. Children with Congenital DM1 present at birth with respiratory insufficiency, talipes equinovarus (clubfoot), feeding difficulties and hypotonia. There is a risk mortality rate in the first year of life. As children grow, they are at risk for intellectual impairment, autistic features, gastrointestinal symptoms, motor delay and a variety of muscle-based symptoms.

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Do We Have Free Will? Neuroscientists Aren’t Sure

MedicalResearch.com Interview with:

Veljko Dubljević, Ph.D., D.Phil. Assistant Professor of Philosophy, Department of Philosophy and Religious Studies, and  Science Technology and Society Program, North Carolina State University Raleigh, NC 27607 

Dr. Veljko Dubljević

Veljko Dubljević, Ph.D., D.Phil.
Assistant Professor of Philosophy,
Department of Philosophy and Religious Studies, and
Science Technology and Society Program,
North Carolina State University
Raleigh, NC 27607 

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

Response: There is considerable controversy about the interpretation of data of the neuroscientific studies done by Benjamin Libet. On the one hand, Libet claimed that his work disproves certain metaphysical conceptions of free will (Libertarianism), whereas it does not disprove others (e.g., Compatibilism). In a nutshell, the reason for these claims is that Libet found preparatory brain activity (Readiness Potentials or RPs) some 500ms before the conscious decision to act was felt by study participants. That seemed to exclude the possibility that mental causation was taking place. At the same time, the onset of movement left a time-window for a ‘veto-decision’. This led Libet to conclude that there is no ‘free will’, but that there is a ‘free won’t’.

On the other hand, there were many criticisms of the study – methodological or substantive. Most notably, Patrick Haggard argued that it is not RPs that are correlates of a decision to act, but Lateralized Readiness Potentials (LRPs). Haggard agreed with many critics of Libet in that RPs could be connected to a range of other phenomena, and that preparatory brain activity that is most important for a decision to act already has to be ‘lateralized’. Namely, the decision to move the left or right arm is critical in this regard, and will lead to RP being focused in one or the other hemisphere, thus making LRPs the point of interest for any conscious decision to act. All in all, Haggard claimed to have replicated Libet’s major findings, with the caveat that timing of LRPs excludes the time-frame for a ‘veto-decision’. This Haggard claimed makes the evidence more in line with the metaphysical doctrine of ‘hard determinism’, which excludes agency and responsibility.

Many other neuroscientists followed Libet’s (and Haggard’s) lead and these experiment became part of ‘lore’ in neuroscience education – many other labs performed similar experiments and claimed to basically replicate the findings.

Our study was the first to review all available evidence.

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Lack of Awareness of Cognitive Issues Presages Alzheimer’s Disease

MedicalResearch.com Interview with:
Joseph Therriault

Integrative Program in Neuroscience 

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

Response: Neurologists have known for a long time that Anosognosia, or unawareness of illness, appears in individuals with Alzheimer’s disease. For example, these patients will have diminished awareness of their memory loss, and will also engage in dangerous behaviors, such as leaving the house to go for a walk, without knowing they are at high risk of getting lost.

However, it was not known if decreased awareness of cognitive problems existed in the pre-dementia phase of Alzheimer’s disease. In our study, we compared the ratings of cognitive decline from the patient and their close relative, who also filled out the same questionnaire. When a patient reported having no cognitive problems but the family member reported significant difficulties, the patient was considered to have poor awareness of illness.

We found that patients who are less aware had increased disease pathology, and were nearly three times as likely to progress to dementia within two years, even when taking into account other factors like genetic risk, age, gender and education. The increased progression to dementia was mirrored by increased brain metabolic dysfunction in regions vulnerable to Alzheimer’s disease.

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How does SURPRISE! Make You Stop What You Are Doing?

MedicalResearch.com Interview with:

Jan R. Wessel, Ph.D. Asst. Professor Department of Psychological and Brain Sciences Department of Neurology Iowa Neuroscience Institute University of Iowa

Dr. Wessel

Jan R. Wessel, Ph.D.
Asst. Professor
Department of Psychological and Brain Sciences
Department of Neurology
Iowa Neuroscience Institute
University of Iowa 

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

Response: We found that the occurence of unexpected events, such as sudden, surprising sounds lead to an automatic engagement of a well-known brain network for action-stopping, thereby leading to a suppression of ongoing motor activity. Specifically, we found that when participants had to stop an action, their ability to do so was significantly improved when the cue to stop was accompanied by a sudden, unexpected sound. This improvement was accompanied by an amplification of the brain activity that is related to action-stopping, and was also accompanied by an increase of suppression of excitability of the motor cortex.  Continue reading

Similar Incidence of Autoimmune and Infectious Brain Inflammatory Disease Encephalitis

MedicalResearch.com Interview with:

Eoin Flanagan, M.B., B.Ch. Mayo Clinic Rochester, Minnesota

Dr. Flanagan

Eoin Flanagan, M.B., B.Ch.
Mayo Clinic
Rochester, Minnesota 

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

 

Response: Traditionally it has been thought that infections (e.g., viruses)  account for the majority of encephalitis cases. Recent discoveries of neural autoantibody markers of encephalitis (e.g., NMDA receptor autoantibodies) have led to an appreciation that encephalitis cases can be caused by the body’s own immune system attacking the brain, what we term autoimmune encephalitis. Continue reading

Lampreys Can Regenerate Severed Spinal Cord – Maybe Humans Can Too

MedicalResearch.com Interview with:
Ona Bloom PhD
“Duluth Boat Show - Sea Lamprey Booth” by USFWSmidwest is licensed under CC BY 2.0Associate Professor, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases,
The Feinstein Institute for Medical Research
Associate Professor, Department of Molecular Medicine,
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell

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

Response: Scientists have known for years that an ancient species of fish called the lamprey has a remarkable ability to rebuild their spinal cord after it’s been severed. After the lamprey spinal cord is cut, they recover from paralysis to fully swimming again in about twelve weeks, without taking any medicines or other treatments. We are studying the lamprey because we want to know the recipe of molecular ingredients that supports successful recovery after spinal cord injury.

The genome of this animal was reported about 5 years ago, in a publication led by my colleagues Dr. Jeramiah Smith at the University of Kentucky and Dr. Weiming Li at Michigan State University.  It turns out that many aspects of the lamprey genome are similar to ours, particularly in the central nervous system. Therefore, we think it is a reasonable expectation that what we learn from lamprey could give us some relevant clues about what might be different about the responses in mammals and other animals that are not good at regenerating their spinal cord.

In this study, we found that the expression of many genes in the spinal cord and brain of lampreys change during their recovery from spinal cord injury. Some of the genes that get activated are similar to what happens when our peripheral nervous system is injured, which is better at regenerating than the central nervous system. We also identified that a pathway called the Wnt pathway plays an important role in the regeneration and recovery process. This is a large, complex network of genes that are important in many biological processes, from embryological development in fruit flies to cancer in humans. Continue reading

Genetics Underlies Differences in Parkinson’s Disease Progression

MedicalResearch.com Interview with:

Rachel Saunders-Pullman, MD, MPH Associate Professor of Neurology Icahn School of Medicine at Mount Sinai Chief, Movement Disorders, Mount Sinai Beth Israel Co-Director Clinical/Translational Research and Research Mentoring Movement Disorders, Department of Neurology, Mount Sinai Beth Israel New York, NY 10003

Dr. Saunders-Pullman

Rachel Saunders-Pullman, MD, MPH
Associate Professor of Neurology
Icahn School of Medicine at Mount Sinai
Chief, Movement Disorders, Mount Sinai Beth Israel
Co-Director Clinical/Translational Research and Research Mentoring
Movement Disorders, Department of Neurology,
Mount Sinai Beth Israel
New York, NY 10003

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

Response: There is a diversity in causes of Parkinson’s Disease (PD), and this may lead to heterogeneity in drug response. While LRRK2 PD due to G2019S mutations may fully mimic idiopathic PD (IPD), cross-sectional study suggests that the course may be slightly milder than IPD. Further, the pathology is heterogeneous with a minority not demonstrating Lewy bodies, and this may also correspond to less severe non-motor features.

To better understand the course of PD associated with the G2019S LRRK2 mutation (the most common LRRK2 mutation), we evaluated motor and cognitive progression in individuals enrolled in the LRRK2 Ashkenazi Jewish Consortium. Subjects were recruited from a Center in Tel Aviv, Israel, Sourasky Medical Center, and from two centers in New York, Columbia University and Mount Sinai Beth Israel. 144 participants were LRRK2 mutation carriers and 401 were not. We utilized all study visits, and constructed linear mixed-effects models to estimate the association between harboring the LRRK2 mutation and rate of change of both motor features- as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS), and cognition, as measured by the Montreal Cognitive Assessment Scale (MoCA). Models adjusted for sex, site, age, disease duration and (for the motor models) cognitive score.

We found a small but significant difference in rate of progression, with LRRK2 PD progressing at 0.69 points/year, and IPD at 1.06 points/year. While the cognitive decline was also less in the LRRK2 PD (-0.10 vs. -0.19 in the IPD, this difference was not statistically different (p=0.08).

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Multiple Sclerosis: Rituximab Had Better Short and Medium Term Outcomes

MedicalResearch.com Interview with:
Fredrik Piehl MD PhD, prof. of Neurology

Neuroimmunology Unit. Dept Clinical Neuroscience
Neurology Dept.
Karolinska University Hospital (Solna)
Stockholm

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

Response: In recent years we have seen a drastic increase in treatment options for relapsing-remitting multiple sclerosis (RRMS). However, it is difficult to deduce long term performance of different drugs based only on data from randomized controlled trials, since such trials are performed in selected patients without major co-morbidities and perhaps also enriched for those with a milder disease course. In addition, most trials only last for two years and lack relevant comparators. This lack of knowledge makes it difficult to predict if a drug will work or not for a given patient, in turn leading to frequent treatment switches but also different treatment practices across countries, regions or even between centers. This is also the case in Sweden, but with the additional aspect that some regions have opted to treat most newly diagnosed RRMS patients with rituximab (Rituxan/Mabthera), a drug not formally approved for RRMS, but with extensive safety data from other indications.

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Babies’ Brain Responses Predict Dyslexic Reading Skills in School

MedicalResearch.com Interview with:

Kaisa Lohvansuu, PhD
Postdoctoral Researcher
Jyväskylä Centre for Interdisciplinary Brain Research
Department of Psychology
University of Jyväskylä 

MedicalResearch.com: What is the background for this study?
Response: Developmental dyslexia, a specific reading disability, has a strong genetic basis: The risk of having developmental dyslexia at school age is eight times higher than usual if either of the parents has reading difficulty. It has been known that dyslexia and also family risk for dyslexia are strongly associated with a speech perception deficit, but the underlying mechanism of how the impaired speech processing leads to reading difficulties has been unclear.

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SVC As Marker of Respiratory Decline in Amyotrophic Lateral Sclerosis

MedicalResearch.com Interview with:

Jinsy Andrews, MD, MS Director of Neuromuscular Clinical Trials Columbia University The Neurological Institute New York, NY 10032 

Dr. Andrews

Jinsy Andrews, MD, MS
Director of Neuromuscular Clinical Trials
Columbia University
The Neurological Institute
New York, NY 10032 

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

Response: The importance of respiratory function in Amyotrophic Lateral Sclerosis (ALS) has long been recognized. Despite ALS being a clinical diagnosis with variable presentation and variable rates of disease progression, all patients experience respiratory symptoms and inevitably die typically from respiratory failure. At present there is no validated biomarker of disease progression or clinical staging system. Direct measure of respiratory function in ALS is important and can be measured using vital capacity. Although the forced maneuver (FVC) has been widely used in patients with ALS, it can underestimate the actual lung capacity by causing fatigue or inducing bronchospasm in patients with ALS. More recently, the slow maneuver (SVC) has been used since it can be obtained from patients with advancing disease which can potentially minimize missing data and may reduce any underestimation of actual lung capacity due to a forceful effort. However, the prognostic value of the decline in SVC is unclear in patients with ALS.

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Parasitic Infection With Toxoplasmosis May Be Linked To Parkinson’s & Alzheimer’s Disease

MedicalResearch.com Interview with:

Under a magnification of 900X, this hematoxylin and eosin-stained (H&E) photomicrograph of a brain tissue specimen revealed a case of neurotoxoplasmosis in a patient who had also been diagnosed with multiple myeloma. Note the Toxoplasma gondii tissue cyst, within which bradyzoites could be seen developing. CDC Image

Rima McLeod, M.D., F.A.C.P, F.I.D.S.A
Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College,
Director, Toxoplasmosis Center,
Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis,
Member Global Health Center, Affiliate CHeSS;
Attending Physician, Chicago Medicine,
The University of Chicago

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

* One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii.
* Approximately fifteen million of these have congenital toxoplasmosis.
* The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites.
* In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process.
* Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior.
* Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases.
* Although neurobehavioral disease is associated with seropositivity, causality is unproven.
* Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality.
* Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases.
* We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design
* To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments?
* We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions.
* To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain.  Continue reading