NeuroDerm Announces Start of Bioequivalence Trial in Healthy Volunteers of ND0701

July 26, 2016

A New Continuous Subcutaneously Delivered Apomorphine Product Candidate for the Treatment of Advanced Parkinson’s Disease

• ND0701 complements the company’s product pipeline for the treatment of advanced Parkinson's disease  
• ND0701's proprietary formulation is designed to improve patient convenience by allowing delivery through a small, disposable, low-volume patch-pump and improve the tolerability and pain associated with current continuous apomorphine therapy -
• Company pursuing an abbreviated EU regulatory pathway based on demonstrating bioequivalence vs. commercially available apomorphine in healthy volunteers -

NeuroDerm Ltd. (Nasdaq:NDRM), a clinical stage pharmaceutical company developing drugs for central nervous system (CNS) disorders, today announced that dosing has started in its EU bioequivalence trial (Trial 101) comparing ND0701, the company’s continuous, subcutaneously delivered liquid apomorphine-base formulation, with commercial continuous, subcutaneously delivered apomorphine-HCl. ND0701 is based on a novel, proprietary formulation of concentrated apomorphine-base that was designed to significantly improve patient convenience by enabling its administration via a small, disposable, low-volume patch-pump, and to improve the local tolerability and pain associated with current commercially available subcutaneously administered continuous apomorphine-HCl. Apomorphine is the most potent dopamine agonist used for the treatment of Parkinson's disease. The company's EU regulatory pathway for ND0701 is based on the demonstration of bioequivalence vs. commercial apomorphine-HCl in healthy volunteers. As previously disclosed, the company is currently designing the clinical and regulatory development plan of ND0701 in the United States.

Trial 101 is a crossover, randomized, two-sequence, 12 hour bioequivalence study that compares the pharmacokinetics, safety and tolerability of ND0701 with those of a reference commercial apomorphine product. The study is expected to enroll a total of 18 healthy volunteers and is expected to be completed in the fourth quarter of this year.

“Following multiple preclinical studies, this first clinical trial of ND0701, based on apomorphine, our second molecule for the treatment of Parkinson's disease, marks the introduction of an important new product candidate by NeuroDerm," said Oded S. Lieberman, PhD, NeuroDerm's CEO. "NeuroDerm's unique technology and knowhow in drug-device combinations that incorporate our novel, proprietary, drug formulations for continuous, subcutaneous delivery is being developed to allow us to offer Parkinson's patients a spectrum of new treatment alternatives aimed at different patient segments at different stages of the disease. ND0701 complements NeuroDerm's product line for treating Parkinson's disease beyond its ND0612 product candidates, which provide continuous subcutaneously administered levodopa/carbidopa, the gold standard therapy in Parkinson's disease. ND0701's proprietary formulation is designed to overcome some of the limitations of commercially available apomorphine formulations, which we believe have prevented their more widespread adoption. We believe that ND0701, if approved, may reposition apomorphine, the most potent dopamine agonist, as an effective therapy with an attractive profile, enabling its increased use as a relevant, non-surgical, convenient treatment alternative for Parkinson's disease patients, including severe patients who face limited treatment options.”

About ND0701
ND0701 contains apomorphine, the most potent dopamine agonist. Apomorphine is the most effective drug for the symptomatic treatment of Parkinson's disease after levodopa, which is considered the gold standard Parkinson's therapy. In addition, Apomorphine is approved both in the United States and in the EU for acute administration as rescue treatment for off periods in Parkinson's disease (currently administered subcutaneously as bolus injections) and only in the EU and not in the United States for continuous, subcutaneously delivered chronic therapy of advanced Parkinson's patients. Current commercial apomorphine formulations, based on apomorphine-HCl, are associated with low tolerability and pain and require daily subcutaneous administration of large volumes that limit its more widespread adoption. ND0701 is being developed as a chronic therapy of Parkinson's disease by continuous subcutaneous apomorphine administration. Based on a proprietary formulation of apomorphine-base, ND0701 is up to five times more concentrated than currently available commercial apomorphine-HCl products and should enable delivery through a small, low-volume, disposable patch-pump. In preclinical studies, ND0701 was also shown to have better local tolerability than a leading commercial apomorphine product. ND0701 is designed to offer superior convenience and better tolerability to current, continuous, subcutaneously administered apomorphine-HCl products.

http://www.globenewswire.com/news-release/2016/07/26/858908/0/en/NeuroDerm-Announces-Start-of-Bioequivalence-Trial-in-Healthy-Volunteers-of-ND0701-a-New-Continuous-Subcutaneously-Delivered-Apomorphine-Product-Candidate-for-the-Treatment-of-Advan.html

Newron to Re-Submit US NDA for Xadago® (Safinamide)

July 26, 2016 

Newron, Zambon, and US WorldMeds announced today the US FDA no longer require any studies to clinically evaluate the potential abuse liability or dependence/withdrawal effects of Xadago.

FDA agrees no additional evaluation of abuse liability or dependence/withdrawal effects in humans is required

Newron to Re-Submit US NDA for Xadago® (Safinamide)

Newron Pharmaceuticals S.p.A. (“Newron”) (SIX: NWRN), a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central nervous system (CNS) and pain, and its partners Zambon S.p.A. and US WorldMeds announced today that the US Food and Drug Administration (FDA) and the Controlled Substance Staff (CSS) in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration no longer require Newron to perform any studies to clinically evaluate the potential abuse liability or dependence/withdrawal effects of Xadago®. The FDA decision was communicated during a meeting with Newron that was scheduled following the March 29, 2016 Complete Response Letter (CRL). 

The CRL did not require submission of any additional new data/studies/analyses for efficacy or safety in patients with Parkinson’s disease, thus Newron will now expedite re-submission of the New Drug Application (NDA) to the FDA. 

Ravi Anand, MD, Newron’s CMO, said: “We thank the FDA and CSS for their help over the last months. Newron’s submission of additional pre-clinical abuse liability studies and additional analyses of the clinical data requested by the CSS led the FDA and CSS to conclude that no further evaluation of the abuse liability or dependence/withdrawal effects of Xadago® were required. Newron and the FDA agreed on the contents of the NDA re-submission which Newron expects to complete by November of this year.”

“We appreciate the exciting development which will allow us to advance the introduction of this potential new treatment option to the one million Americans living with Parkinson’s disease,” said P. Breckinridge (“Breck”) Jones, CEO of US WorldMeds. 

“We are very pleased that the FDA has allowed the re-submission of Xadago® in the next months. This reinforces once more our commitment in finding innovative therapies for patients suffering from PD and other Central Nervous System diseases,” said Elena Zambon, President of Zambon. 

About Xadago® (safinamide)

Safinamide is a new chemical entity with a unique mode of action, including selective and reversible MAO-B-inhibition and blocking of voltage dependent sodium channels, which leads to modulation of abnormal glutamate release. Clinical trials have established its efficacy in controlling motor symptoms and motor complications in the short term, maintaining this effect over 2 years. Results from 24 month double-blind controlled studies suggest that safinamide shows statistically significant effects on motor fluctuations (ON/OFF time) without increasing the risk of developing troublesome dyskinesia. This effect may be related to its dual mechanism acting on both the dopaminergic and the glutamatergic pathways. Safinamide is a once-daily dose and has no diet restrictions due to its high MAO-B/MAO-A selectivity. Zambon has the rights to develop and commercialize Xadago® globally, excluding Japan and other key territories where Meiji Seika has the rights to develop and commercialize the compound. The rights to develop and commercialize Xadago® in the USA have been granted to US WorldMeds, by Zambon. 

References:

Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson’s disease.

Borgohain, Rupam; Szasz, Jozsef; Stanzione, Paolo; Meshram, Chandrashekhar; Bhatt, Mohit H et al. (2014).

Movement disorders : official journal of the Movement Disorder Society vol. 29 (10) p. 1273-80.

Anand R: Safinamide is associated with clinically important improvement in motor symptoms in fluctuating PD patients as add-on to levodopa (SETTLE). 17th International Congress of Parkinson’s Disease and Movement Disorders, Sydney, Australia, June 16-20, 2013. 

About Parkinson’s disease

PD is the second most common chronic progressive neurodegenerative disorder in the elderly after Alzheimer’s disease, affecting 1-2% of individuals aged ≥ 65 years worldwide. The prevalence of the PD market is expected to grow in the next years due to the increase in the global population and advancements in healthcare that contribute to an aging population at increased risk for PD. The diagnosis of PD is mainly based on observational criteria of muscular rigidity, resting tremor, or postural instability in combination with bradykinesia. As the disease progresses, symptoms become more severe. Early-stage patients are more easily managed on L-dopa. L-dopa remains as the most effective treatment for PD, and over 75% of the patients with PD receive L-dopa. However, long term treatment with L-dopa leads to seriously debilitating motor fluctuations, i.e. phases of normal functioning (ON-time) and decreased functioning (OFF-time). Furthermore, as a result of the use of high doses of L-dopa with increasing severity of the disease, many patients experience involuntary movements known as L-dopa-Induced Dyskinesia (LID). As the disease progresses, more drugs are used as an add-on to what the patient already takes, and the focus is to treat symptoms while managing LID and the “off-time” effects of L-dopa. Most current therapies target the dopaminergic system that is implicated in the pathogenesis of PD, and most current treatments act by increasing dopaminergic transmission that leads to amelioration of motor symptoms. 

References:

BMC Oertel. European Handbook of Neurological Management, Vol1, Chapter 14 & 15, 2011.

NICE PD guideline, 2006. 

About Newron Pharmaceuticals

Newron (SIX: NWRN) is a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central nervous system (CNS) and pain. The Company is headquartered in Bresso near Milan, Italy. Xadago® (Safinamide) has received marketing authorization for the treatment of Parkinson’s disease in the European Union and Switzerland and is commercialized by Newron’s Partner Zambon. US WorldMeds holds the commercialization rights in the US. Meiji Seika has the rights to develop and commercialize the compound in Japan and other key Asian territories. In addition to Xadago® for Parkinson’s disease, Newron has a strong pipeline of promising treatments for rare disease patients at various stages of clinical development, including sarizotan for patients with Rett syndrome and ralfinamide for patients with specific rare pain indications. Newron is also developing NW-3509 as the potential first add-on therapy for the treatment of patients with positive symptoms of schizophrenia.

For more information, please visit: www.newron.com.

About US WorldMeds

US WorldMeds is a specialty pharmaceutical company dedicated to developing, licensing and commercializing unique and significant specialty pharmaceuticals that address unmet medical needs or overcome limitations of existing products. Through sound science and targeted commercialization, the Kentucky-based company continually strives to identify specialty and orphan products for diseases with limited patient populations. US WorldMeds’ portfolio includes Revonto® (dantrolene sodium for injection) for the treatment of malignant hyperthermia, MYOBLOC® (rimabotulinumtoxinB) Injection for the treatment of cervical dystonia in adults and APOKYN® (apomorphine hydrochloride injection) for the acute, intermittent treatment of hypomobility, “off” episodes associated with advancing Parkinson’s disease. In addition, US WorldMeds is working on the development of a non-narcotic drug product (Lofexidine) for the treatment of opiate withdrawal symptoms. For more information about US WorldMeds, visit www.usworldmeds.com. 

About Zambon

Zambon is a leading Italian pharmaceutical and fine-chemical multinational company that has earned a strong reputation over the years for high quality products and services. Zambon is well-established in 3 therapeutic areas: respiratory, pain and woman care, and is very strongly committed to its entry into the CNS space. Zambon S.p.A. produces high quality products thanks to the management of the whole production chain which involves Zach (Zambon chemical), a privileged partner for API, custom synthesis and generic products. The Group is strongly working on the treatment of the chronic respiratory diseases as asthma and BPCO and on the CNS therapeutic area with Xadago® (safinamide) for the Parkinson treatment. Zambon is headquartered in Milan and was established in 1906 in Vicenza. Zambon is present in 19 countries with subsidiaries and almost 2,700 employees with manufacturing units in Italy, Switzerland, France, China and Brazil. Zambon products are commercialized in 84 countries.

For details on Zambon please see: www.zambongroup.com.

Important Notices

This document contains forward-looking statements, including (without limitation) about (1) Newron’s ability to develop and expand its business, successfully complete development of its current product candidates and current and future collaborations for the development and commercialisation of its product candidates and reduce costs (including staff costs), (2) the market for drugs to treat CNS diseases and pain conditions, (3) Newron’s anticipated future revenues, capital expenditures and financial resources, and (4) assumptions underlying any such statements. In some cases these statements and assumptions can be identified by the fact that they use words such as “will”, “anticipate”, “estimate”, “expect”, “project”, “intend”, “plan”, “believe”, “target”, and other words and terms of similar meaning. All statements, other than historical facts, contained herein regarding Newron’s strategy, goals, plans, future financial position, projected revenues and costs and prospects are forward-looking statements. By their very nature, such statements and assumptions involve inherent risks and uncertainties, both general and specific, and risks exist that predictions, forecasts, projections and other outcomes described, assumed or implied therein will not be achieved. Future events and actual results could differ materially from those set out in, contemplated by or underlying the forward-looking statements due to a number of important factors. These factors include (without limitation) (1) uncertainties in the discovery, development or marketing of products, including without limitation negative results of clinical trials or research projects or unexpected side effects, (2) delay or inability in obtaining regulatory approvals or bringing products to market, (3) future market acceptance of products, (4) loss of or inability to obtain adequate protection for intellectual property rights, (5) inability to raise additional funds, (6) success of existing and entry into future collaborations and licensing agreements, (7) litigation, (8) loss of key executive or other employees, (9) adverse publicity and news coverage, and (10) competition, regulatory, legislative and judicial developments or changes in market and/or overall economic conditions. Newron may not actually achieve the plans, intentions or expectations disclosed in forward-looking statements and assumptions underlying any such statements may prove wrong. Investors should therefore not place undue reliance on them. There can be no assurance that actual results of Newron’s research programmes, development activities, commercialisation plans, collaborations and operations will not differ materially from the expectations set out in such forward-looking statements or underlying assumptions. Newron does not undertake any obligation to publicly up-date or revise forward looking statements except as may be required by applicable regulations of the SIX Swiss Exchange where the shares of Newron are listed. This document does not contain or constitute an offer or invitation to purchase or subscribe for any securities of Newron and no part of it shall form the basis of or be relied upon in connection with any contract or commitment whatsoever.

https://www.freshnews.com/newron-to-re-submit-us-nda-for-xadago-safinamide/20160726

New approaches to understanding Alzheimer's and Parkinson's disease

July 26, 2016

In a study presented today at the Alzheimer's Association International Conference 2016, researchers at the Douglas Mental Health University Institute have explored how some people may develop the hallmarks of Alzheimer's or Parkinson's but never develop symptoms.

Alzheimer's is typified by the build-up of amyloid protein in the brain, and Parkinson's disease by the loss of a key chemical messenger in the brain called dopamine.

However, it's becoming clear that individuals can exhibit these changes but show no changes in their memory, thinking or day-to-day function. Using brain imaging data from large-scale studies into both diseases, the team identified regions of the brain associated with resilience to these changes, such as a key region in the memory centre of the brain which was preserved despite the build-up of amyloid. 

By mapping these potential protective networks in the brain, the researchers hope to identify potential new approaches to treat the disease as well as ways to indicate those most at risk.

Dr Rosa Sancho, Head of Research at Alzheimer's Research UK, said:

"The observation that some individuals can exhibit Alzheimer's or Parkinson's disease changes in their brainwithout showing any symptoms has raised important questions for researchers trying to tackle these diseases. This study suggests that there may be differences in the brains of individuals who are more resilient to diseases like Alzheimer's, providing clues to what brain areas may be most important for that protection. Understanding the mechanisms underpinning resilience to neurodegenerative diseases across the population can help to uncover new targets for treatments or approaches to intervene to delay the onset in those most at risk."

Provided by: Alzheimer's Research UK

http://medicalxpress.com/news/2016-07-approaches-alzheimer-parkinson-disease.html?

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Clinical advances in gene therapy for central nervous system disorders

July 25, 2016

Credit: Mary Ann Liebert, Inc., publishers

The encouraging results of early stage clinical studies and the tremendous amount of preclinical data demonstrating the feasibility and promise of gene therapy to treat disorders of the central nervous system (CNS) are driving new advances for the treatment of both genetic and acquired neurodegenerative diseases. Recent progress in therapeutic adeno-associated virus (AAV)-mediated gene transfer strategies and prospects for the future are presented in a Review article in Human Gene Therapy.

n the article "Adeno-Associated Virus-Based Gene Therapy for CNS Diseases" coauthors Michael Hocquemiller, Laura Giersch, Mickael Audrain, Samantha Parker, and Nathalie Cartier, of Lysogene (Neuilly sur Seine), Université Paris Descartes (Paris), Université Paris-Sud and Université Paris-Saclay (Orsay), and CEA, DSV, I2BM, MIRCen (Fontenay-aux-Roses), France, describe the expanding scope of CNS diseases being targeted with gene therapy. These include lysosomal storage diseases, Alzheimer disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA). The researchers discuss the rapid advances in the development of new viral vectors and compare the advantages and limitations of different gene therapy delivery strategies to treat CNS dis-orders.

"The global disease burden of neurodegenerative diseases is increasing dramatically with the aging of populations in the developed world," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. "Gene therapy promises to be a critically important part of the response of the biomedical research community to this enormous public health challenge."

More information: Michaël Hocquemiller et al, Adeno-Associated Virus-Based Gene Therapy for CNS Diseases, Human Gene Therapy (2016).  DOI: 10.1089/hum.2016.087 

Journal reference: Human Gene Therapy  

Provided by: Mary Ann Liebert,Inc 
http://medicalxpress.com/news/2016-07-clinical-advances-gene-therapy-central.html

New theory explains how beta waves arise in the brain

July 25, 2016

Jones led a team that has posited a new theory of how beta rhythms arise in the brain, backed by evidence from humans, animal models and computer simulation. Credit: Brown University


Beta rhythms, or waves of brain activity with an approximately 20 Hz frequency, accompany vital fundamental behaviors such as attention, sensation and motion and are associated with some disorders such as Parkinson's disease. Scientists have debated how the spontaneous waves emerge, and they have not yet determined whether the waves are just a byproduct of activity, or play a causal role in brain functions. Now in a new paper led by Brown University neuroscientists, they have a specific new mechanistic explanation of beta waves to consider.

The new theory, presented in the Proceedings of the National Academy of Sciences, is the product of several lines of evidence: external brainwave readings from human subjects, sophisticated computational simulations and detailed electrical recordings from two mammalian model organisms.

"A first step to understanding beta's causal role in behavior or pathology, and how to manipulate it for optimal function, is to understand where it comes from at the cellular and circuit level," said corresponding author Stephanie Jones, research associate professor of neuroscience at Brown University. "Our study combined several techniques to address this question and proposed a novel mechanism for spontaneous neocortical beta. This discovery suggests several possible mechanisms through which beta may impact function."

Making waves

The team started by using external magnetoencephalography (MEG) sensors to observe beta waves in the human somatosensory cortex, which processes sense of touch, and the inferior frontal cortex, which is associated with higher cognition.

They closely analyzed the beta waves, finding they lasted at most a mere 150 milliseconds and had a characteristic wave shape, featuring a large, steep valley in the middle of the wave.

The question from there was what neural activity in the cortex could produce such waves. The team sought to recreate the waves using a computer model of a cortical circuitry, made up of a multilayered cortical column that contained multiple cell types across different layers. Importantly, the model was designed to include a cell type called pyramidal neurons, whose activity is thought to dominate the human MEG recordings.

They found that they could closely replicate the shape of the beta waves in the model by delivering two kinds of excitatory synaptic stimulation to distinct layers in the cortical columns of cells: one that was weak and broad in duration to the lower layers, contacting spiny dendrites on the pyramidal neurons close to the cell body; and another that was stronger and briefer, lasting 50 milliseconds (i.e., one beta period), to the upper layers, contacting dendrites farther away from the cell body. The strong distal drive created the valley in the waveform that determined the beta frequency.

Meanwhile they tried to model other hypotheses about how beta waves emerge, but found those unsuccessful.

With a model of what to look for, the team then tested it by looking for a real biological correlate of it in two animal models. The team analyzed measurements in the cortex of mice and rhesus macaques and found direct confirmation that this kind of stimulation and response occurred across the cortical layers in the animal models.

"The ultimate test of the model predictions is to record the electrical signals inside the brain," Jones said. "These recordings supported our model predictions."

Beta in the brain

Neither the computer models nor the measurements traced the source of the excitatory synaptic stimulations that drive the pyramidal neurons to produce the beta waves, but Jones and her co-authors posit that they likely come from the thalamus, deeper in the brain. Projections from the thalamus happen to be in exactly the right places needed to deliver signals to the right positions on the dendrites of pyramidal neurons in the cortex. The thalamus is also known to send out bursts of activity that last 50 milliseconds, as predicted by their theory.

With a new biophysical theory of how the waves emerge, the researchers hope the field can now investigate whether beta rhythms affect or merely reflect behavior and disease. Jones's team in collaboration with Professor of neuroscience Christopher Moore at Brown is now testing predictions from the theory that beta may decrease sensory or motor information processing functions in the brain. New hypotheses are that the inputs that create beta may also stimulate inhibitory neurons in the top layers of the cortex, or that they may may saturate the activity of the pyramidal neurons, thereby reducing their ability to process information; or that the thalamic bursts that give rise to beta occupy the thalamus to the point where it doesn't pass information along to the cortex.

Figuring this out could lead to new therapies based on manipulating beta, Jones said.

"An active and growing field of neuroscience research is trying to manipulate brain rhythms for optimal function with stimulation techniques," she said. "We hope that our novel finding on the neural origin of beta will help guide research to manipulate beta, and possibly other rhythms, for improved function in sensorimotor pathologies."

Explore further: New study to test unusual hypothesis on beta brainwaves

More information: Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice, www.pnas.org/cgi/doi/10.1073/pnas.1604135113 

Journal reference: Proceedings of the National Academy of Sciences 

Provided by: Brown University 

 http://medicalxpress.com/news/2016-07-theory-beta-brain.html

Imaging technique shows in living brain what was once only visible in cadavers

Chris Wood
July 22, 2016

The researchers were able to use a PET scanner to image synapse health in living patients  (Credit: Yale PET center)

Our understanding of prevalent brain disorders such as Alzheimer's disease is constantly evolving, but when observing how such conditions affect synapses, researchers have had to rely on post-mortem observations. A Yale University team of scientists has developed and tested a technique that could revolutionize how we observe the progress of common brain disorders. In the long run, it could lend a hand in the development of treatments for everything from Alzheimer's to epilepsy.

Synapses are the junctions between the brain's nerve cells; they're essential to how the brain works, allowing signals to pass from one neuron to another. Certain conditions cause damage to synapses, which stops the brain from functioning in a normal, healthy manner.

The new method makes use of a positron emission tomography (PET) scanner, combined with a radioactive tracer, which is a chemical compound with an atom swapped out for a radioactive isotope, which can then be detected by sensitive equipment. The tracer is injected into the body, and binds with a particular protein present in synapses in the brain. 

The PET scanner is then used to observe the radioactive emissions from the tracer, with a custom-made mathematical tool interpreting the data to describe synaptic density, or the number of synapses firing in any one area. That information describes how healthy the brain is, with decreased density indicating that a condition is interrupting or inhibiting normal function. Up until now, we've only been able to study synaptic density through autopsies. 

The researchers have already tested out the imaging technique, applying it to both baboons and human patients. The trials confirmed that the method works as intended, revealing synaptic loss in three patients with epilepsy. They are currently planning future studies on conditions including schizophrenia, depression, Alzheimer's and Parkinson's disease.

Scientists have already developed methods for observing neuron behavior on a brain-wide scale and even built a window to the brain, but with current methods of synapse study being limited to autopsy observations, a new imaging technique for synapses could have a big impact on our understanding of neurological disorders, and might even help us develop new treatments. 

"This opens the door to follow the natural evolution of synaptic density with normal aging and follow how drugs can alter synapses or synapse formation." said study co-author Rich Carson.

Full details of the research are published online in the journal Science Translational Medicine.: Yale University

http://www.gizmag.com/brain-synapse-health-imaging/44501/?utm_source=Gizmag+Subscribers&utm_campaign=0e48e743b4-UA-2235360-4&utm_medium=email&utm_term=0_65b67362bd-0e48e743b4-92059757

Partially Paralyzed Man Completes 101 Skydive Jumps in a Single Day for Parkinson's Research

July 25, 2016

Kevin Burkart

Kevin Burkart was attempting to do 300 skydives in one day in 2012 when a snowmobile accident in northern Minnesota paralyzed his left arm. 

"It was devastating, but I pushed forward," Burkart, 44, tells PEOPLE. "I wasn't going to let that slow me down." 

The professional competition and tandem skydiving instructor (who has been jumping since 2002) wasn't just doing it for the thrill. In 1999, his father, Gary, was diagnosed with Parkinson's disease. Burkart has since made it his mission to help find a cure. 

"It's the second most common neurodegenerative disease," he says. "But it doesn't make any noise." 

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Burkart, who cares for his father who is now in the late stages of Parkinson's, says it's painful to see someone you love go from being healthy to using a cane and then a walker. 

"The people who have it are normally older. They're humble and just going quietly into the night," he says. "It's amazing how quickly you go from being a baby and being taken care of to then taking care of your parents." 

Between three skydiving events in 2008, 2010 and 2012, Burkart raised $250,000 for research into the disease. 

My name is Kevin Burkart and I skydive for Parkinson’s Disease.

Then, on June 15, despite high winds gusting up to 29 mph, he completed 101 jumps in just 24 hours in Prior Lake, Michigan. 

Throughout the day, 400 people came to watch him at Skydive Twin Cities. There were also food trucks, information booths, speakers, yoga and massages available to everyone who came to the big event. 

"It was a really special day," says Burkart who recently got married. "I almost broke my ankle a couple times and it beat the heck out of me, but it felt so good doing this and knowing I was raising money for this disease. It might be too late for my father, but it might help others." 

Skydivers in that particular area typically jump at 13,000 feet, but Burkart was jumping from a height of 2,000 feet due to the amount of jumps he attempted. 
Although he came short of his goal to complete 300 skydives that day, Burkart, who raised $128,000 at the event, says he still feels like he accomplished a great deal. 

"This is just the beginning," he says. "We have a lot more fighting to do."

Video:http://bcove.me/9iktzssr

https://interactive.tegna-media.com/video/embed/embed.html?id=2191847&type=video&title=300%20Imperfect%20Jumps&site=89&playerid=6918249996581&dfpid=32805352&dfpposition=Video_prestream_external%C2%A7ion=home

http://www.people.com/article/kevin-burkart-skydiver-parkinsons-research-for-dad

Meds up hospitalization for dehydration, heat-linked illness

July 25, 2016

(HealthDay)—Among veterans, initiation of many commonly-used medications is associated with increased risk of hospitalization for dehydration or heat-related illness, according to research published online July 4 in the Journal of Clinical Pharmacy and Therapeutics.

Lisa M. Kalisch Ellett, Ph.D., from the University of South Australia in Adelaide, and colleagues conducted a retrospective analysis using prescription event symmetry analysis for 6,700 veterans with incident hospital admission for dehydration or heat-related illness.

The researchers found that the risk of incident hospital admission for dehydration or heat-related illness was significantly increased following initiation of anticoagulants, cardiovascular medicines, nonsteroidal anti-inflammatory drugs, antipsychotics, antidepressants, and anticholinergic agents. There was variation in the risk of hospital admission for dehydration or heat-related illness from 1.17 for selective serotonin reuptake inhibitor to 2.79 for angiotensin converting enzyme inhibitor plus diuretic combination product. Initiation of anticonvulsants, anti-Parkinson's agents, hypnotics, anxiolytics, or antihistamines was not significantly associated with hospital admission for dehydration or heat-related illness.

"Many commonly used medicines were found to be associated with increased risk of hospitalization for dehydration or heat-related illness," the authors write. "Prescribers and patients should be aware of the potential for medicines to be associated with increased risk of dehydration and heat-related illness."

http://medicalxpress.com/news/2016-07-meds-hospitalization-dehydration-heat-linked-illness.html

Fox Trial Finder Expands to Accelerate Research in Atypical Parkinsonism

Posted by  Loren DeVito, PhD, 
 July 25, 2016

Atypical parkinsonisms are rare conditions that share symptoms and, in some cases, biology with Parkinson’s disease. By studying atypical parkinsonisms, researchers can advance therapies for these conditions and, perhaps, for Parkinson’s.

Today, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) announced the expansion of its clinical research matching tool, Fox Trial Finder, to include studies and a registration option for atypical parkinsonisms.

“There is much to learn about atypical parkinsonisms and their connections to each other and to Parkinson’s disease,” said Todd Sherer, PhD, CEO of MJFF. “Expanding Fox Trial Finder to be more inclusive of these conditions will speed trial recruitment and thereby the pace of discovery and drug development for the millions affected.”

Atypical parkinsonism diseases — corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, and progressive supranuclear palsy — share some of the motor symptoms of Parkinson’s disease (PD), such as tremor, slowness, rigidity and walking/balance problems. Some of these conditions share biology with Parkinson’s as well. As in PD, accumulation of the protein alpha-synuclein is characteristic of dementia with Lewy bodies and multiple system atrophy.

There are no effective disease-modifying therapies currently available for these conditions. The expansion of Fox Trial Finder aims to increase engagement in atypical parkinsonism research and help uncover potential new therapies for both Parkinson’s and associated diseases.

Fox Trial Finder first launched in 2011 to help solve the recruitment challenge in Parkinson’s research. By matching volunteers to the clinical studies that need them, Fox Trial Finder helps bring better treatments to patients faster. To date, Fox Trial Finder has registered more than 57,000 research participants.

https://www.michaeljfox.org/foundation/news-detail.php?fox-trial-finder-expands-to-accelerate-research-in-atypical-parkinsonism

Parkinson's: Mutant gene interaction may pave the way for new treatments

July 24, 2016

Inhibiting the activity of the LRKK2 gene mutation "may slow progression of Parkinson's disease-associated pathology."

New research finds that an interaction between a mutant gene and an abundant brain protein shows similarities with clinical indicators of Parkinson's disease. These findings could lead to new treatments for the disease.

Parkinson's disease (PD) is a progressive neurological disease that affects around 60,000 Americans every year. Its symptoms can be life-changing and include a general slowness of movement, tremors, and rigidity, although symptoms differ from person to person.

Drugs and therapies can help to manage the condition, but there is currently no known cure.

Researchers at the University of Alabama at Birmingham (UAB) have discovered what could be a significant finding in the path to developing a cure for PD.

Although it is thought that environmental factors cause many cases of PD, the disease can also develop through genetic factors. Several genetic factors have been shown to increase a person's risk of developing Parkinson's disease, although exactly how these make some people more susceptible to the condition has previously been unclear.

The most common genetic cause of Parkinson's disease is a mutation in a gene called leucine-rich repeat kinase 2 (LRRK2).

Preclinical drugs block mutant gene, slow Parkinson's progress

The research team found that the mutated LRKK2 gene causes inclusions, or abnormal structures, within the neurons of the brain. These inclusions are made of a protein called alpha-synuclein, which are found in the brains of people with PD after death.

It was found that in in-vitro tests, small, potent concentrations of preclinical drugs that inhibit the mutant variant of the LRKK2 gene reduced the formation of the alpha-synuclein inclusions.

The study, published in Journal of Neuroscience, suggests that the interaction between mutant LRRK2 kinase and alpha-synuclein "may uncover new mechanisms and targets for neuroprotection."

The authors write: "These results demonstrate that alpha-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of Parkinson's disease-associated pathology."

Laura A. Volpicelli-Daley, Ph.D., and Andrew B. West, Ph.D. led the research team at the Center for Neurodegeneration and Experimental Therapeutics, of the UAB Department of Neurology.

LRRK2 kinase inhibitors: Promising treatment for Parkinson's

Volpicelli-Daley and colleagues note that the potential clinical applications for these LRRK2-associated neuroprotection strategies require testing in other preclinical models of Parkinson's disease.

"These data give us hope for the clinical potential of LRRK2 kinase inhibitors as effective therapies for Parkinson's disease. The LRRK2 kinase inhibitors may inhibit the spread of pathologic alpha-synuclein, not only in patients with LRRK2 mutations, but in all Parkinson's disease patients. Future studies to validate the safety and efficacy of the LRRK2 inhibitors will be necessary before testing the inhibitors in human clinical trials. "Laura A. Volpicelli-Daley, Ph.D.

Alpha-synuclein also plays a role in the development of dementia and is linked with Alzheimer's disease and other neurodegenerative disorders.

Volpicelli-Daley applied low concentrations of pre-formed fibrils of alpha-synuclein to neurons to cause modifications associated with PD. This model was used to test the effects of the mutant LRRK2 kinase, G2019S-LRRK2, on the formation of inclusions.

Another key finding from the study was that G2019S-LRRK2 enhanced alpha-synuclein inclusion formation in dopamine neurons in a part of the brain called the substantia nigra pars compacta.

This area of the brain dies in people with PD, and so this observation confirms a link between the G2019S-LRRK2 mutation and PD pathogenesis.

The researchers indicate that the G2019S-LRRK2 mutation may increase the risk of PD by boosting the amounts of mobile - as opposed to membrane-bound - alpha-synuclein in neurons.

It is hoped that these findings will shape future research into the causes of the disease and the LRKK2-inhibiting drugs.

Written by Hannah Nichols

http://www.medicalnewstoday.com/articles/311846.php?