XenoPort, Inc. (Nasdaq:XNPT) announced today that it has been awarded a grant from The Michael J. Fox Foundation (MJFF) for Parkinson’s Research to support preclinical studies to explore XP23829 for its ability to protect against neurodegeneration in experimental preclinical models of Parkinson’s disease. The grant of $347,075 was awarded under the Foundation's Therapeutics Development Initiative Program aimed at supporting preclinical development of Parkinson's disease therapies that have the potential for fundamentally altering disease course and improving treatment of symptoms. “Evaluating drugs that could potentially slow the progression of Parkinson’s disease is a high-priority research area for The Michael J. Fox Foundation,” said Kuldip Dave, PhD, associate director of research programs at MJFF. “We are encouraged by research that suggests that fumaric acid esters could slow the progression of the neurodegenerative process. We are hopeful that XenoPort’s efforts to this end could help to speed progress toward a breakthrough treatment for patients with Parkinson’s disease.” XenoPort is evaluating XP23829, a fumaric acid ester compound and a prodrug of monomethyl fumarate (MMF). Fumaric acid ester compounds have shown immuno-modulatory and neuroprotective effects in cell-based systems and preclinical models of disease. Dimethyl fumarate (DMF), also a fumaric acid ester compound and a prodrug of MMF, has been shown to be effective in clinical trials in patients with relapsing-remitting multiple sclerosis (RRMS) and psoriasis. A potential shortcoming of DMF-based therapy is that patients can suffer from gastrointestinal adverse events. The biological mechanisms underlying the beneficial effects of fumaric acid ester prodrugs may be due to Nrf2 activation by MMF. Nrf2 activation is thought to combat oxidative neurodegeneration by increasing the genetic expression of a number of antioxidant enzymes and downregulating, or reducing, production of proinflammatory molecules. In human genetic studies, patients with genetic sequences associated with high Nrf2 transcriptional activity also showed decreased risk of developing Parkinson’s disease or an increased age of onset of the disease. In preclinical models of Parkinson’s disease, MPTP-induced neurotoxicity of dopaminergic neurons was reduced by activation of Nrf2 either through addition of Nrf2-inducing compounds or by over expression of Nrf2.
XenoPort plans to examine the ability of XP23829 to prevent or decrease neurodegeneration in a preclinical model in which the neurotoxin MPTP selectively attacks dopamine neurons like those affected by Parkinson’s disease. The studies are designed to examine how the timing of the treatment may effect the progression of neurodegeneration in this model. Various treatment regimens will be examined to determine if XP23829 could prevent damage once neurodegenerative processes have occurred.Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, said, “We thank The Michael J. Fox Foundation for enabling XenoPort to evaluate XP23829 for its possible benefits to Parkinson’s patients. This will allow us to extend our preclinical studies of XP23829, which we hope will provide new insights to treating Parkinson’s disease.” XenoPort is developing novel fumaric acid esters compounds that are prodrugs of MMF. Preclinical studies of one of these compounds, XP23829, have shown reduced gastric irritation compared to DMF in preclinical models. About Parkinson's Disease Parkinson’s disease is a chronic, degenerative neurological disorder that results from the loss of dopamine-producing nerve cells in the brain. Current treatments for Parkinson’s disease are able to reduce the symptoms of the disease but are not able to treat the underlying neurodegenerative processes that lead to a decline in physical and cognitive functions that affects some patients with Parkinson’s disease. An oral drug that could slow or prevent neurodegeneration might be able to decrease the disability progression that some patients experience in the disease. It is estimated that as many as 1.5 million people in North America are living with Parkinson’s disease. According to the National Institute of Neurodegenerative Disease and Stroke (NIH), the average age of onset is 60, though some people are diagnosed at age 40 or younger. About The Michael J. Fox Foundation for Parkinson’s Research As the world’s largest private funder of Parkinson’s research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson’s disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson’s patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $297 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson’s research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson’s disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson’s awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. Now through December 31, 2012, all new and increased giving to The Michael J. Fox Foundation, as well as gifts from donors who have not given since 2010 or earlier, will be matched on a dollar-for-dollar basis with the $50-million Brin Wojcicki Challenge, launched by Sergey Brin and Anne Wojcicki.
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