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Saturday, December 22, 2018

Multiple Sclerosis Bladder Issues: Three Most Common Problems for Men and Women






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Several household chemical exposures are associated with pediatric-onset multiple sclerosis


Abstract

BACKGROUND:
There is limited information about the potential associations of multiple sclerosis (MS) and commonly used household chemicals.
METHODS:
We performed a case-control study of exposures to common household chemicals during childhood in children with MS and healthy pediatric controls. Exposures to household products were collected from a comprehensive questionnaire (http://www.usnpmsc.org/Documents/EnvironmentalAssessment.pdf) completed by parents at the time of enrollment in the study. 

Cases included children diagnosed with MS or clinically isolated syndrome with at least two silent T2 bright lesions on MRI, recruited within 4 years of disease onset from 16 pediatric MS clinics in the USA. Multivariate analyses using logistic regression were adjusted for possible confounders including age, sex, race, ethnicity, mother's highest level of education, and urban versus rural living.
RESULTS:
Questionnaire responses to household chemicals were available for 312 eligible cases (median age 15.7 years, 63% girls) and 490 healthy controls (median age 15.0, 57% girls). Exposure to rodenticides (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.35-3.26, P ≤ 0.001), weed control agents (OR 1.99, 95% CI 1.36-2.92, P ≤ 0.001) and products for plant/tree disease control (OR 2.72, 95% CI 1.54-4.82, P ≤ 0.001) anytime during childhood were associated with an increased risk for pediatric-onset MS in adjusted and multiple comparisons analyses.
CONCLUSIONS:

Our findings suggest that exposure to specific household chemicals during early childhood is associated with the risk of developing pediatric-onset MS. Future studies are needed to elucidate a causal relationship and the exact agents involved.
READ MORE


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Biomarkers in multiple sclerosis

Abstract

Substantial effort has been made over the last six decades to identify biomarkers for multiple sclerosis that can improve disease diagnosis, predict disease progression, and improve clinical outcomes. However, to date, few of these findings have proven clinically useful. In this review, we address the current state of MS biomarker research. We start by discussing biomarkers currently in clinical use including Oligoclonal bands, MRI, and JC viral titers. We go on to discuss other potential biomarkers from MS serum and cerebrospinal fluid including Markers of neurodegeneration including neurofilament and GFAP, the monocyte macrophage marker CD163, the glial activation marker YKL-40, the B cell chemoattractant CXCL13, miRNA and mRNA, myelin reactive t cells, Kir4.1 antibodies, osteopontin, and microbiome associated lipopeptides. Finally, we discuss the current state of MS genetic studies and how genetics may offer simple, reliable testing for MS susceptibility and progression.

KEYWORDS:

Biomarkers; Multiple sclerosis
PMID:
 
26143623
 
DOI:
 
10.1016/j.clim.2015.06.015
[Indexed for MEDLINE]



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Acorda Therapeutics Announces FDA Approval of INBRIJA™ (levodopa inhalation powder) for Parkinson's

12/21/2018

  • First and Only FDA-Approved Inhaled Levodopa for Intermittent Treatment of OFF Episodes in People with Parkinson’s Taking Carbidopa/Levodopa 
  • Expected to be Available by Prescription in First Quarter 2019 
  • Based on Innovative ARCUS® Technology Platform for Inhaled Drug Delivery 
  • Conference Call on Monday, December 24, 2018 at 8:30am Eastern Time ARDSLEY, N.Y.--


(BUSINESS WIRE)-- Acorda Therapeutics, Inc. (Nasdaq:ACOR) today announced that the U.S. Food and Drug Administration approved INBRIJA™ for intermittent treatment of OFF episodes in people with Parkinson’s disease treated with carbidopa/levodopa. OFF episodes, also known as OFF periods, are defined as the return of Parkinson’s symptoms that result from low levels of dopamine between doses of oral carbidopa/levodopa, the standard oral baseline Parkinson’s treatment.

“Today’s approval of INBRIJA marks a major milestone for both Acorda and the Parkinson’s community, for whom we are gratified to have developed this much needed therapy,” said Ron Cohen, M.D., Acorda President and CEO. “This milestone resulted from over two decades of research and development, beginning in the laboratory of Dr. Robert Langer at Massachusetts Institute of Technology, through years of enormous perseverance and ingenuity by the entire Acorda team.”

“Despite being on treatment, patients may experience OFF periods as Parkinson’s progresses, which can be disruptive,” said Todd Sherer, Ph.D., CEO, The Michael J. Fox Foundation. “The Foundation provided funding for the early clinical development of INBRIJA because patients told us that OFF periods were one of their most serious issues. We knew we had to help address this unmet need, and this approval is a significant step forward for the community as it provides a new option to manage these gaps in symptom control.”


“In the clinical study program, INBRIJA established its safety prole and demonstrated clinically meaningful improvements in motor function, as measured by the UPDRS Part III,” said Robert A. Hauser, M.D., MBA, Professor of Neurology and Director of the Parkinson's Disease and Movement Disorders Center at the University of South Florida. “INBRIJA helps address a significant unmet need for people with Parkinson’s, and we look forward to adding this new treatment option to our armamentarium.” 

FDA approval of INBRIJA was based on a clinical program --
                   click to continue reading


Wednesday, December 19, 2018

Long Haul Paul bringing MS awareness to rural America


Long Haul Paul riding 1 million miles for MS awareness
LONG HAUL PAUL RIDING 1 MILLION MILES FOR MS AWARENESS THROUGHOUT RURAL AMERICA


As  much as I enjoy riding all over the country and hanging out at motorcycle rallies and trade shows, it only takes a minute to remind me of the reason I left the security of a steady job and decided to dedicate my foreseeable future to bring education, inspiration and hope to others living every day with the unpredictable symptoms and progression of multiple sclerosis (MS).
It was a chance meeting at the American International Motorcycle Exposition (AIMExpo) in Las Vegas this past October that quickly reminded me of my purpose for being there. I was a guest of Yamaha, showing off my new Star Venture motorcycle, as well as handing out my brochures and Chasing the Cure wristbands. Inside the Mandalay Bay Convention Center, I stood on my feet for twelve hours each of the four days of the event. The first two days were for dealers and press, and the last two days were for the general public. It is the largest motorcycle trade show in the country. It was exhausting but great exposure for my journey, as I am always on the hunt for new corporate sponsors, as well as trying to grow my social media followers.
Some time on Saturday afternoon, a middle-aged couple approached me after seeing the graphics on my bike showing that I was Chasing the Cure for MS. It didn’t take them long to tell me their adult son had just been diagnosed with MS a week earlier. They were clearly shaken by the news, sad, scared and a bit overwhelmed by all of it. I started as I always do, inquiring about their son’s symptoms, where he was at regarding treatment and stressing how important it was to find an MS specialist. After a while, they realized that I was actually a patient as well, bringing a few tears but also a bit of relief. I gave them resources and websites to help them navigate the vast information available as well as offered to call or speak to their son if they thought it would help. By the time they left my booth, the tears and fears had been wiped away and replaced with a round of hugs. I made them promise they would call me when they had more questions. They left with some information and hope.
Paul Pelland and trunk of Yamaha motorcycleForty-five minutes with a couple who must have had some interest in motorcycles (we never did actually talk about bikes) quickly reminded me of the importance of my mission and reassured me that the struggles I face and the sacrifices I make while continuing to share my story are indeed worth it.
After six years on the road, 350,000 miles and over $150,000 raised for charity, I am shifting my  journey once again. As of 2019, I will no longer be speaking at pharmaceutical-sponsored events, but will continue to share my story at unbranded and unbiased patient programs presented by a non-profit organization called MS Views and News (MSVN). Based out of Miami, MSVN has been providing free educational events across the country for many years. After spending quite bit of time and energy trying to find an MS charity that had the same goals as I did and was willing to help promote my efforts and fundraising events, I am excited to be partnering with MSVN President Stuart Schlossman and his organization.
Together, we are developing a series of presentations to deliver information to remote areas of the country where MS patients are not getting the same level of help or resources that bigger communities receive. The Ride to Reach Rural America initiative will utilize me on my motorcycle to bring education, inspiration and hope along the back roads of America, one small town at a time.
Much like the events I was already speaking at, I will be delivering a bit of inspiration, some insight into my disease and treatment history, and for the first time, be allowed to add humor and a slideshow to my talks. No longer will my talk be scrutinized by legal and compliance departments or the FDA, as it had been in the past. Being able to tell my story, share my journey and inspire others freely will allow me to reach more people at each event. For the first time in six years, I don’t have to be anonymous and can provide my audiences with the means to follow me or contact me through social media.
That’s right folks,  Paul P. (actual patient) is dead.
LONGHAULPAUL is alive, on the road and coming to a small town near you.
Like, share, follow or get the hell out of his way!
HELP ME get to these rural MS locations. 
Please donate by clicking here

Source:   

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What prevents remyelination? New stem cell research reveals a critical culprit

December 18, 2018, 
University at Buffalo

neuron Credit: CC0 Public Domain        

New research on remyelination, the spontaneous regeneration of the brain's fatty insulator that keeps neurons communicating, could lead to a novel approach to developing treatments for multiple sclerosis (MS) and other inflammatory diseases.
The pre-clinical findings published today in Cell Reports by a University at Buffalo team reveal that activation of a specific transcription factor induces in  a phenomenon called pathological quiescence. This is when adult stem cells are rendered incapable of responding to injury by producing -forming oligodendrocytes. The failure to remyelinate is the key feature of MS.
The paper defines the role of the previously undescribed transcription factor known as PRRX1 in human progenitor cells, the  that generate myelin-forming oligodendrocytes.
Current MS research focuses largely on drugs that induce the differentiation of human oligodendrocyte progenitors. In contrast, the UB research presents a novel concept for the development of new drugs based on blocking the pathological quiescence of progenitors.
"The idea that pathological quiescence of progenitors could prevent  in MS is distinct from the current pre-clinical strategies making their way into trial," explained Fraser Sim, Ph.D., senior author and associate professor of pharmacology and toxicology in the Jacobs School of Medicine and Biomedical Sciences at UB.
"We found that switching this gene on could cause problems in myelin repair by blocking the proliferation of the oligodendrocyte progenitor cell, the stem cell-like precursor that is responsible for all myelin regeneration in the adult brain," he said.
The research demonstrated that PRRX1 expression results in the cell cycle arrest and quiescence of oligodendrocyte progenitors, which disabled the production of myelin.
In an animal model of leukodystrophy, the group of genetic disorders in which myelin fails to form or is destroyed in children, Sim said that pathological quiescence induced by PRRX1 prevented cell colonization of white matter and effective myelin regeneration by transplanted human oligodendrocyte progenitors.
They also found that blocking expression of this transcription factor prevented the negative effects of proinflammatory cytokines, such as interferon-γ, which regulates its expression.
"We found that blockade of PRRX1 expression prevents the negative effects of interferon-γ, suggesting that PRRX1 expression might be a viable target in , such as multiple sclerosis, where interferon-γ may prevent successful myelin regeneration," said Sim.


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FDA Gives Green Light to Phase 2 Trial of NurOwn Stem Cell Therapy in Progressive MS Patients

December 19, 2018

The U.S. Food and Drug Administration (FDA) has approved BrainStorm Cell Therapeutics‘ request to open a Phase 2 clinical trial testing the safety and effectiveness of its proprietary NurOwn mesenchymal stem cell (MSC) treatment in progressive multiple sclerosis (MS) patients.
The request was in the form of Investigational New Drug (IND) application, and BrainStorm plans to launch the study in early 2019.
“We are excited about the launch of early testing of this cell-based approach to treating progressive MS, for which there are few treatment options,” Bruce Bebo, executive vice president of research at the National MS Society, said in a press release. “We look forward to better understanding the potential benefits and safety of this and other cell-based therapies for MS.”
Stem cells have the ability to develop into different cell types, and to replace damaged or dying cells in the body. There are different types of stem cells, and therapies based on these cells are being investigated for several diseases, including MS.
NurOwn cells are MSCs obtained from a patient’s bone marrow — the spongy tissue inside bones — and grown in the lab under patented conditions in order to induce the cells to secrete high levels of neurotrophic factors (NTF), molecules that support the growth, survival, and differentiation of neurons. These MSC-NTF cells are then injected back into the patient intravenously or into the spinal canal.
Experiments with mice suggest that injected NurOwn stem cells do not themselves replace damaged cells. Instead, the lab treatment customizes MSCs, converting them into biological factories that secrete high levels of NTFs, which in turn encourage neural stem cells to replace damaged cells.


 #stemcelltherapy

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#Ampyra Significantly Improves Walking Ability As Reported by MS Patients, Phase 3 Trial Shows

December 19, 2018

Treatment with Ampyra (dalfampridine) for 24 weeks leads to sustained and clinically meaningful improvements in walking ability as reported by multiple sclerosis (MS) patients with gait difficulties, according to a study analyzing results from a Phase 3 trial.
More than 90 percent of MS patients have difficulty walking, which reduces their independence and negatively affects their quality of life and productivity.
Ampyra (prolonged-release dalfampridine tablets) is an approved MS medication marketed by Acorda Therapeutics in the U.S. It is the first therapy specifically approved to help improve walking in adults with MS. A generic version of #Ampyra was made available this year in the U.S. by Mylan. In Europe, the medicine is approved under the brand name Fampyra, being marketed by Biogen.
An international group of researchers involved in the clinical trial ENHANCE — a large study evaluating Ampyra’s efficacy — conducted the present study to see whether the therapy could improve, in a clinically meaningful way, the walking ability of MS patients based on data from the trial.
Continue Reading



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Each Major Risk Factor (Like Genes, Smoking and Obesity) Can Affect Disease Course, Study Finds

Risk factors often associated with multiple sclerosis (MS), such as genetic background, obesity and smoking, contribute independently to the disease’s variability and may be an early influence on progression, a study reported.
MS, a neurodegenerative and autoimmune disease, is associated with both genetic and environmental risk factors. Although both have been thoroughly investigated, the “processes contributing to heterogeneity in the clinical manifestation of the disease remain unclear,” the researchers wrote.
Each Major Risk Factor (Like Genes, Smoking and Obesity) Can Affect Disease Course, Study Finds


Multiple studies show that each patient’s characteristics at disease onset — such as age, number of impaired functional domains (NIFDs; functions ranging from walking and balance, to problems with vision, fatigue, or limb numbness or pain), time to second relapse (TT2R), and early relapse activity (ERA) — can help to predict MS activity and progression. But factors are also likely to play a role in early disease presentation.
To pinpoint the mechanisms involved in disease variability and progression, researchers at Case Western Reserve University investigated the influence of those factors with known links to early disease presentation.
Their study analyzed data on 1,515 people in the Accelerated Cure Project Repository, an open-access resource containing clinical records from a U.S. population of MS patients. Machine learning and mathematical models were used to assess the relevance of each measure for each disease outcome.

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