Michael J. Fox Foundation Awards $2.4M For Parkinson's Research

The Michael J. Fox Foundation (MJFF) for Parkinson's Research today announced approximately $2.4 million in total funding to nine research teams under its Target Validation initiative. This annual MJFF program provides intellectual and financial resources to help push potential Parkinson's drug targets forward toward clinical trials and ultimately the nearly 5 million Parkinson's patients worldwide.

Founded in 2000, the foundation is named for the famed actor who suffers from Parkinson's. The foundation says it has funded $123 million in research to date.

"The discovery of a new potential therapeutic target generates great excitement among patients and researchers," says Katie Hood, CEO of The Michael J. Fox Foundation. "But to attract an industry sponsor with the resources and expertise to chaperone it through optimization, preclinical work and ultimately clinical testing, that target needs a critical mass of evidence behind it, demonstrating that it is involved in the disease and that manipulating it impacts symptoms or progression. MJFF's Target Validation program helps accumulate this evidence, reducing the risk of investment for industry and building the case for prioritization of the
most promising targets in the pipeline."

Target validation is an essential and historically under-resourced phase of drug development in which researchers work to determine whether a molecule or mechanism of interest is a true drug target, the foundation says. While researchers have continued to identify novel targets in recent years through genetic, biochemical and epidemiological studies, a lack of funding for validation studies has long been a major roadblock to the efficient translation of these discoveries into practical therapies that benefit people living with Parkinson's.

Projects funded in this cohort of Target Validation awardees fall into three categories: targets for therapies to alleviate symptoms of Parkinson's; approaches focused on dyskinesias, the excessive, uncontrollable movements brought on by long-term dopamine replacement therapy; and targets with potential to slow or stop progression of Parkinson's, something no currently approved treatment has been proven to do.

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Drug Slows and May Halt Parkinson's Disease

Northwestern University researchers have discovered a drug that slows – and may even halt – the progression of Parkinson’s disease. The drug rejuvenates aging dopamine cells, whose death in the brain causes the symptoms of this devastating and widespread disease.

D. James Surmeier, the Nathan Smith Davis professor and chair of physiology at Northwestern University’s Feinberg School of Medicine, and his team of researchers have found that isradipine, a drug widely used for hypertension and stroke, restores stressed-out dopamine neurons to their vigorous younger selves. The study is described in a feature article in the international journal Nature, which will be published online June 10.

Dopamine is a critical chemical messenger in the brain that affects a person’s ability to direct his movements. In Parkinson’s disease, the neurons that release dopamine die, causing movement to become more and more difficult.

Ultimately, a person loses the ability to walk, talk or pick up a glass of water. The illness is the second most common neurodegenenerative disease in the country, affecting about 1 million people. The incidence of Parkinson’s disease increases with age, soaring after age 60.

“Our hope is that this drug will protect dopamine neurons, so that if you began taking it early enough, you won’t get Parkinson’s disease, even if you were at risk. ” says Surmeier, who heads the Morris K. Udall Center of Excellence for Parkinson’s Disease Research at Northwestern. “It would be like taking a baby aspirin everyday to protect your heart.”

Isradipine may also significantly benefit people who already have Parkinson’s disease. In animal models of the disease, Surmeier’s team found the drug protected dopamine neurons from toxins that would normally kill them by restoring the neurons to a younger state in which they are less vulnerable.

The principal therapy for Parkinson’s disease patients currently is L-DOPA, which is converted in the brain to dopamine. Although L-DOPA relieves many symptoms of the disease in its early stages, the drug becomes less effective over time. As the disease progresses, higher doses of L-DOPA are required to help patients, leading to unwanted side-effects that include involuntary movements. The hope is that by slowing the death of dopamine neurons, isradipine could significantly extend the time in which L-DOPA works effectively.

“If we could double or triple the therapeutic window for L-DOPA, it would be a huge advance,” Surmeier says.

The work by Surmeier’s group is particularly exciting because nothing is known to prevent or slow the progression of Parkinson’s disease.


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Therapy for Restless Legs May Trigger Compulsive Gambling

A class of drugs commonly used to treat the neurological disorder restless legssyndrome (RLS) may cause compulsive gambling, researchers say.

Compulsive gambling with extreme losses -- in two cases, greater than $100,000 -- has been tied to the treatment, according to a Mayo Clinic study.

The Mayo Clinic study is the first to describe compulsive gambling in RLS patients who are being treated with medications that stimulate dopamine receptors in the brain. The Mayo Clinic report appeared in the Jan. 23 issue of Neurology.

The extent of this therapy-related compulsive gambling problem is unknown, the researchers say. Apparently, it occurs only in a small number of RLS patients treated with drugs called dopamine agonists. Considering this potential side effect of dopamine agonists, the Mayo Clinic authors suggest that physicians screen all RLS patients for compulsive behaviors while taking a thorough medical history prior to prescribing dopamine agonists. Patients should be monitored closely forsigns of compulsive behaviors once dopamine agonist treatment has begun. The report suggests that the compulsion to gamble worsened with increasing doses of the dopamine agonists.

Pathological gambling is an impulse control disorder. In 2005, Mayo Clinic physicians reported this disorder as a side effect of dopamine agonist therapy in 11 Parkinson disease patients.

"Although pathologic gambling has already been recognized in patients with Parkinson disease who often took high doses of dopamine agonists, the current report suggests that pathological gambling is not restricted to patients with Parkinson disease -- and also can occur at low dosages," says Maja Tippmann-Peikert, M.D., the lead author of the Mayo Clinic report on restless legs syndrome. "Physicians should not only monitor Parkinson disease patients for this behavior but also screen their RLS patients who may be on much lower doses of dopamine agonists."

This includes encouraging the patient, family members and friends to report negative behaviors to the patient's physician, the researchers say.

Fortunately, pathological gambling seems to be reversible when the dose of the dopamine agonist is reduced or the patient is transitioned to an alternative medication, they say. It is crucial that these adjustments are initiated before significant gambling debts develop, and relationships and careers are damaged, they add.


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