Our scientific understanding of early onset Parkinson's disease is continually expanding.

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The APDA National Young Onset Center regularly posts Parkinson’s news and information on new Parkinson’s research. We offer research on Parkinson’s having to do with the potential causes of the disease, promising new treatments, and avenues worth investigating with regard to an eventual cure.

NEW DIRECTIONS IN PARKINSON'S TREATMENTS

Adapted from e-Parkinson Post, a blog of Parkinson Society Canada. December, 2009.

Current Parkinson's medications treat the symptoms but do not stop the progression of the disease. While there is no cure for PD to date, what follows is a review of some promising new drugs that could change the way Parkinson's disease is treated.

CONTINUOUS DOPAMINERGIC STIMULATION

The standard oral medication for handling motor fluctuations in PD is levodopa. However, for some people, levodopa's beneficial effects wear off before the next dose of medication is due. Infusion therapies may offer people with PD an alternative, when oral medications are no longer effective. This type of treatment aims to provide a more continuous stimulation of the brain receptors for dopamine.

Infusion therapies / DUODOPA

There is a new technology in which Duodopa, a concentrated gel-form of levodopa/carbidopa, is pumped through a small tube into the duodenum so it goes into the bowel on a continuous basis. One advantage of this style of medication delivery is that "you can formulate the exact dose, at certain times of the day, in a much more precise way than when using oral preparations; so you can adjust the dose by 1 mg rather than in 50 mg steps," says Dr. Mark Guttman, Director of the Centre for Movement Disorders in Markham, Ontario.

Duodopa therapy does have some drawbacks: it requires a surgical procedure which could lead to complications, the pump and tubing could be subject to technical problems, it requires careful monitoring and nursing support, and some people find it burdensome to carry a pump at all times. "It's a complicated way of giving a medication..." says Dr. Anthony Lang, Director of the Morton & Gloria Shulman Movement Disorder Centre at Toronto Western Hospital. "It's better suited to people who are taking levodopa many times a day and have bad, and often unpredictable, motor fluctuations." Guttman notes, "It could be seen as an option for people who are considering deep brain stimulation (DBS) surgery but either don't qualify for DBS or don't want to take the risks.

Although Duodopa is not yet available in the United States, it is coming. Last year, Solvay Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track designation to the development program for levodopa/carbidopa intestinal gel. Once a drug receives Fast Track designation, early and frequent communication between the FDA and the drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.

ENHANCING THE EFFECT OF DOPAMINIE

A new monoamine oxidase B inhibitor

Monoamine oxidase B inhibitors (MAO-B compounds) enhance the effect of dopamine by preventing its breakdown. International phase III clinical trials are underway for a new investigative drug to determine its effectiveness and safety as an add-on dose to either levodopa or dopamine agonist medications.

LOOKING AHEAD

Dr. Jonathan Brotchie, senior scientist at the Toronto Western Research Institute, highlights three promising drugs that are currently being studied and that could change Parkinson's treatment:

Fipamezole

Fipamezole is a drug which, when taken with dopamine medication, appears to do two things: reduce the problem of dyskinesia and increase the time the dopamine medication works. "I think this could change the way we treat Parkinson's in a relatively short time," says Brotchie.

BIIB014

The experimental drug BIIB014 is one of the first non-dopamine approaches to treating PD. "It reverses a different chemical imbalance in the brain than our current therapies," says Brotchie. "Because it is non-dopaminergic, we anticipate that it won't have the same side effects as current dopamine therapy."

Preliminary studies have shown that BIIB014 can successfully do two things: One, alleviate Parkinson's symptoms, when given on its own. "That's probably the first time we've had a drug which isn't replacing dopamine that can do that," says Brotchie. Two, it appears that, when added to existing therapies, BIIB014 can improve the action of those therapies, decreasing the "off" time between the action of each pill. "This means that you either have to take fewer tablets every day or each tablet works longer."

PYM50028 / Cogane

"Cogane has potential to restore the dopamine system in the brain, not just provide symptomatic benefit," says Brotchie.

Glial cell-derived neurotrophic factor (GDNF) is a protein made in the brain. It helps brain cells grow when the brain is developing or recovering from injury. For the past decade, scientists have been exploring ways to increase the levels of GDNF in the Parkinson's brain to help cells survive or even grow back. Previous approaches have involved injecting GDNF into the brain through surgery or gene therapy. Cogane offers the possibility of delivering GDNF to the brain via a pill, thereby switching on the brain's ability to make GDNF.

Noting that the animal data and early human data on safety and dosage look promising, Brotchie says, "I think Cogane offers the best hope today for a drug that could actually reverse the disease. And if you could reverse the disease early enough, you could change its impact on your life. Parkinson's would then be something that you could be diagnosed with but, if you received the drug early enough, and if the drug lives up to its promise, you could imagine that it might start to reverse symptoms and even reverse the disease process."

LEARN MORE

• What's Next in Parkinson's Treatments? (Webcast)
  Presented by Dr. Jeff Bronstein at the Young Onset Conference, Irvine, CA 2012