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

Nearly a Million People Live with Parkinson’s Disease and Number Expected to Grow

MedicalResearch.com Interview with:

Dr-James Beck

Dr. Beck

James Beck, Ph.D., Chief Scientific Officer
Adjunct Associate Professor
Department of Neuroscience and Physiology
New York University Langone School of Medicine

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

Response: The most frequently cited study for prevalence in the US was based on a door-to-door survey conducted in 1978 in a rural county in Mississippi.  Only 26 cases of Parkinson’s disease (PD) were identified.  That has been extrapolated to our current US population of 330,000,000 people.  To give a sense of how long ago that was, Microsoft was considered a startup company.  Therefore, to provide an improved estimate of who has Parkinson’s disease, the Parkinson’s Foundation lead the Parkinson’s Prevalence study to do just that, using datasets that were from more geographically and ethnically diverse communities that can better reflect the US population as a whole.

The main finding is that we know now that there are nearly 1,000,000 people living with PD – and that number is expected to increase dramatically as our population ages. (The biggest risk factor for Parkinson’s disease is age.)

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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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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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Gabapentin and Pregabalin Should Be Used Cautiously in Hemodialysis Patients

MedicalResearch.com Interview with:

Dr. Julie H. Ishida MD Department of Medicine, Division of Nephrology University of California, San Francisco and San Francisco Veterans Affairs Medical Center

Dr. Ishida

Dr. Julie H. Ishida MD
Department of Medicine, Division of Nephrology
University of California, San Francisco and
San Francisco Veterans Affairs Medical Center

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

Response: Gabapentin and pregabalin are used for the management of symptoms such as neuropathic pain, itching, and restless leg syndrome in patients receiving hemodialysis. However, hemodialysis patients may be particularly vulnerable to adverse events related to these agents, which are cleared by the kidney, but there is limited data evaluating their risk in this population.

Gabapentin and pregabalin use were associated with risk for altered mental status, fall, and fracture, and in some cases, even at doses that would be considered safe for use in this population.  Continue reading

Guillain-Barré Syndrome With and Without Zika

MedicalResearch.com Interview with:

Dr. Emilio Dirlikov, PhD Office of Epidemiology and Research, Puerto Rico Department of Health Epidemic Intelligence Service Division of Scientific Education and Professional Development CDC

Dr. Dirlikov

Dr. Emilio Dirlikov, PhD
Office of Epidemiology and Research, Puerto Rico Department of Health
Epidemic Intelligence Service
Division of Scientific Education and Professional Development
CDC

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

Response: After reporting local Zika transmission in December 2015, the Puerto Rico Department of Health (PRDH), US Centers for Disease Control and Prevention (CDC), and University of Puerto Rico began identifying cases of Guillain-Barré syndrome (GBS), testing specimens, and conducting follow-up telephone interviews after patients left the hospital.

Through these efforts, we were able to characterize acute clinical features and long-term disability of GBS associated with Zika infection by analyzing data from GBS patients with and without evidence of Zika infection.

This investigation increases scientific and medical understanding of Guillain-Barré syndrome following Zika infection, provides insight into the disease processes involved in GBS following Zika infection, and adds to growing evidence of a causal association between Zika and GBS.  Continue reading

Higher Connectivity of Brain Networks Linked to Increased Risk of Psychopathology

MedicalResearch.com Interview with:

Maxwell Elliott Clinical psychology PhD student Working with Ahmad Hariri and the Moffitt & Caspi lab Duke University

Maxwell Elliott

Maxwell Elliott
Clinical psychology PhD student
Working with Ahmad Hariri and the Moffitt & Caspi lab
Duke University

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

Response: The traditional clinical science model identifies individuals who meet specific criteria for mental illness diagnoses (e.g. Depression, Anxiety) and compares them to “healthy” controls to find brain correlates of mental illness.  However, this approach often overlooks the high rates of comorbidity and shared symptamatology across mental illnesses. Emerging research has identified a general factor of psychopathology that accounts for shared risk among internalizing, externalizing, and thought disorders across diverse samples.

This general factor of psychopathology has been called the p-factor. In our study we investigate the brain correlates of the p-factor using a data-driven analysis of resting state functional connectivity. We find that higher p-factor scores and associated risk for common mental illness maps onto hyper-connectivity between visual association cortex and both frontoparietal and default mode networks.

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Epilepsy Patients Have Small Increased Risk of Unnatural Death

MedicalResearch.com Interview with:

Dr Hayley Gorton PhD MPharm MRPharmS FHEA Research Associate Centre for Pharmacoepidemiology and Drug Safety Research Division of Pharmacy & Optometry| Faculty of Biology, Medicine & Health University of Manchester

Dr. Gorton

Dr Hayley Gorton PhD MPharm MRPharmS FHEA
Research Associate Centre for Pharmacoepidemiology and Drug Safety Research
Division of Pharmacy & Optometry| Faculty of Biology, Medicine & Health
University of Manchester

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

Response: It is already known that people with epilepsy are at a higher risk of death than those without epilepsy but we didn’t know much about the risks of different types of death. Unnatural death (mainly accident and suicide) accounts for a very small number of all deaths but, compared to people without epilepsy, people with epilepsy are three times more likely to die by accident and twice as likely to die by suicide. Within these broad categories, persons with epilepsy are five times more likely to die specifically by accidental poisoning with medication, and three times more likely to die by intentionally poisoning themselves with medication. Opioid painkillers and medicines for mental illness were the ones most commonly used in poisoning deaths among people with epilepsy and those without epilepsy. Antiepileptic drugs were taken relatively infrequently-they were involved in about 10% of poisoning deaths in people with epilepsy.  Continue reading

Simple Screening Tool Predicts Parkinson’s Patients At Risk of Dementia

MedicalResearch.com Interview with:

Benjamin Dawson, B.Sc.  MD Candidate 2020

Benjamin Dawson

Benjamin Dawson, B.Sc.
MD Candidate 2020

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

Response: Dementia in Parkinson’s Disease is one of its most feared complications, and may happen eventually to most patients if they reached advanced age. Identifying those at especially high risk of dementia has important potential implications – it would facilitate clinical counselling, it has treatment implications (e.g. knowing a person is likely to get dementia in the near future would probably steer you away from certain medications and towards others).  Most critically, it can help select patients for trials to prevent dementia.

While several factors that show high risk for dementia in Parkinson’s disease have previously been described, these have yet to shape patient-care, either because they are not very strong predictors, or they are not user-friendly.  So, we designed a very simple clinical screening tool, called the Montreal Parkinson’s Risk of Dementia Scale (MoPaRDS).  It took predictors of dementia that were established from large-scale studies and boiled them down into a simple 8-point scale that uses information that you can get in a simple office visit.  The 8 predictors were being over 70, being male, having a blood pressure drop with standing, showing early mild cognitive changes, having a symmetric bilateral disease (that is, one side not clearly worse than the other), experiencing falls or freezing, having experienced hallucinations, and having symptoms of REM sleep behavior disorder (‘acting out’ the dreams at night).

When we tested the scale in a combined cohort of 607 patients with Parkinson’s (of whom 70 developed dementia over mean follow-up of 4.4-years) a positive MoPaRDS screen (≥4 out of 8 items) identified 14-fold increased risk of dementia compared to a negative screen. We recommend dividing the scale into three categories; low-, intermediate- and high-risk. Those in the highest score group (MoPaRDS, 6-8) had a 14.9% risk of developing dementia each year, while those with the lowest scores (MoPaRDS, 0-3) had only 0.6% annual risk.  So, these simple measures can be pretty powerful predictors of dementia. Continue reading

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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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

Study Finds Modest Survival Increase in Parkinson’s Patients Who Receive Deep Brain Stimulation

MedicalResearch.com Interview with:
Dr. Frances M. Weaver PhD
Hines VA Hospital
Center of Innovation for Complex Chronic Healthcare
Hines, IL 60141

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

Response: Research has shown that deep brain stimulation (DBS) for Parkinson’s disease (PD) improves motor function and this improvement is sustained. There is also improvement in quality of life after DBS. However, it is not known whether DBS also effects survival. A few studies that have examined survival have had mixed results.

In the current study we compared survival for a large cohort of persons with Parkinson’s disease who underwent DBS to a match group of persons with PD who were managed medically.

We found a modest improvement in survival for persons with Parkinson’s disease who underwent DBS compared to individuals who did not.

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Mitochondrial Link To Cocaine Addiction Explored

“cocaine photo” by Imagens Evangélicas is licensed under CC BY 2.0MedicalResearch.com Interview with:
Mary Kay Lobo, PhD

Associate Professor
University of Maryland School of Medicine
Department of Anatomy and Neurobiology
Baltimore, MD 21201 

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

Response: Altered energy balance has been studied in drug abuse but the fundamental source of energy, mitochondria, has not been well examined.  In this study we found that a molecular regulator of mitochondrial fission (division) is increased in the nucleus accumbens, a major brain reward region, of rodents exposed to repeated cocaine and postmortem samples of cocaine dependent individuals.  We further found that mitochondrial fission is increased in a nucleus accumbens neuron subtype in rodents that self-administer cocaine. Pharmacological blockade of mitochondrial fission can prevent physiological responses to cocaine in this neuron subtype while reducing cocaine-mediated behaviors.  Finally, genetic reduction of mitochondrial fission in this neuron subtype in the nucleus accumbens can reduce drug (cocaine) seeking in rodents previously exposed to cocaine. In contrast, increasing mitochondrial fission, in this neuron subtype, enhances cocaine seeking behavior.

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Deep Brain Stimulation Helpful For Some Visual Hallucinations

MedicalResearch.com Interview with:

Dr. Foltynie

Dr. Foltynie

Thomas Foltynie MD PhD
Senior Lecturer and Honorary Consultant Neurologist
Unit of Functional Neurosurgery Institute of Neurology and
National Hospital for Neurology and Neurosurgery
University College London

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

Response: Stimulation of the Nucleus Basalis of Meynert can enhance cholinergic innervation of the cortex in animal models and has been previously reported to have beneficial cognitive effects in a single patient with Parkinson’s Disease dementia.

In this double blind crossover trial, six patients with Parkinson’s Disease underwent low frequency stimulation to the NBM bilaterally.  While there were no consistent objective improvements in cognitive performance, there was a marked reduction in visual hallucinations in two of the participants. .

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Chronic Inflammation in Midlife May Predispose To Smaller Brain Volumes and Memory Ability In Seniors

MedicalResearch.com Interview with:
Keenan A. Walker, PhD
Johns Hopkins University School of Medicine
Baltimore, MD

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

Response: There is quite a bit of evidence linking immune function with dementia. For example, several of the risk genes for Alzheimer’s disease are known to play a key role in immune functioning and the regulation of inflammation. We conducted the current study to determine whether systemic inflammation earlier in life might be a risk factor for neurodegeneration decades later. This long temporal window allows us to get closer to understanding causality. That is, which comes first – systemic inflammation or brain volume loss.

Using a large community sample, we found that individuals with higher levels of blood inflammatory markers during midlife tended to have smaller brain volumes in select regions and reduced memory ability as older adults. We found the strongest associations between systemic inflammation and brain volume loss in brain regions most vulnerable Alzheimer’s disease.

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Refined Biomarker Model Can Guage Risk of Alzheimer’s In Patients With Mild Cognitive Impairment

MedicalResearch.com Interview with:
Ingrid S. van Maurik, MSc
Department of Neurology and Alzheimer Center
Department of Epidemiology and Biostatistics
Amsterdam Neuroscience
VU University Medical Center
Amsterdam, the Netherlands

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

Response: CSF and MRI biomarkers are increasingly used in clinical practice, but their diagnostic and prognostic value is not perfect. Furthermore, criteria do not specify how to deal with conflicting or borderline results, or how to take patient characteristics into account. Therefore, optimal use of these biomarkers in clinical practice remains challenging.

As part of the ABIDE project, we constructed biomarker-based prognostic models (CSF, MRI and combined) that enable prediction of future Alzheimer’s disease, or any type of dementia, in individual patients with mild cognitive impairment. When using these models, any value can be entered for the variables, resulting in personalized probabilities with confidence intervals.

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Weakening Neural Connections Can Eliminate Fearful Memories

MedicalResearch.com Interview with:

Jun-Hyeong Cho MD PhD Department of Molecular, Cell and Systems Biology University of California, Riverside Riverside, CA 92521

Dr. Jun-Hyeong Cho

Jun-Hyeong Cho MD PhD
Department of Molecular, Cell and Systems Biology
University of California, Riverside
Riverside, CA 92521

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

Response: To survive in a dynamic environment, animals develop fear responses to dangerous situations. For these adaptive fear responses to be developed, the brain must discriminate between different sensory cues and associate only relevant stimuli with aversive events.

In our current study, we investigated the neural mechanism how the brain does this, using a mouse model of fear learning and memory. Our study demonstrates that the formation of fear memory associated with an auditory cue requires selective synaptic strengthening in neural pathways that convey the auditory signals to the amygdala, an essential brain area for fear learning and memory.

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Refined Deep Brain Stimulation Turns On ‘As Needed’ To Treat Tremors

MedicalResearch.com Interview with:

Howard Jay Chizeck ScD Professor, Electrical Engineering Adjunct Professor, Bioengineering Co-Director UW Biorobotics Laboratory Graduate Program in Neuroscience UW CoMotion Presidential Innovation Fellow Research Thrust Testbed Co-Leader

Prof. Chizeck

Howard Jay Chizeck ScD
Professor, Electrical Engineering
Adjunct Professor, Bioengineering
Co-Director UW Biorobotics Laboratory
Graduate Program in Neuroscience
UW CoMotion Presidential Innovation Fellow
Research Thrust Testbed Co-Leader

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

Response: Essential Tremor is treated using Deep Brain Stimulation (DBS) in some patients. Current clinical practice involves Deep Brain Stimulation with an “always on” stimulation. This causes extra battery drain, because stimulation is applied when not needed. Also excessive stimulation is not necessarily a good thing,

Our work is aimed at adjusting the stimulation, so that it comes on and turns off only when needed to suppress tremor symptoms.

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Extended-Release Amantadine Reduces Dyskinesia in Parkinson’s Disease

MedicalResearch.com Interview with:
Rajesh Pahwa MD
Department of Neurology
University of Kansas Medical Center, Kansas City, KS,

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

Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia.

This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017).

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