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Science News

Scientists Take Step Toward Personalized Cell Therapy for Parkinson’s

Researchers funded in part by the Parkinson’s Disease Foundation (PDF) have made an important advance toward cell therapy for Parkinson’s disease (PD). They report in the March 28 issue of Cell Reports that they have successfully transplanted healthy neurons into the brains of monkeys. Their results indicate progress toward the goal of one day being able to transplant healthy cells into the brains of people with PD to replace dopamine neurons lost to the disease.

Su-Chun Zhang, M.D., Ph.D., Marina Emborg, M.D., Ph.D., and colleagues at the University of Wisconsin, Madison, worked with three rhesus monkeys with parkinsonian symptoms caused by chemical exposure.

To create healthy neurons, Dr. Zhang and his team worked with “artificial” stem cells. They took the monkeys’ own skin tissue, and in the lab, they reprogrammed it back into a stem cell-like state. In this state, the cells can be manipulated into any type of cell in the body including neurons needed in the brain. Dr. Emborg and her team then transplanted into each monkey the healthy cells taken from its own skin tissue.

Results

  • The healthy cell transplants developed successfully into neurons in the monkeys’ brains.
  • Scientists found neither signs of immune rejection nor tumors — two problems seen in previous studies.
  • The cell transplants survived up to six months, much longer than in previous studies.
  • However, no improvement in the monkeys’ parkinsonian symptoms was observed — probably due to the small size of the cell transplant. (Note that symptom relief was not a goal of this initial study.)

What Does it Mean?

“Artificial” stem cells— also called induced pluripotent stem cells (iPSCs)— hold great promise for treating the motor symptoms of PD. Yet in previous studies, animals had rejected the transplants, much as a person rejects an organ transplant from an unmatched donor.

The new study is important because it is the first to overcome immune rejection by using personalized medicine — transplanting cells back into the same animal from which they were taken. It demonstrates the potential of the technique. But many questions remain to be answered before potential cell therapies can be tested in people. For example, scientists need to know whether the transplants are safe and whether there are side effects. Then the technique needs to be proven to improve symptoms in animals and people.

 

Investigational Drug May Reduce “Off-Time” in Parkinson’s

A new study adds evidence that istradefylline, an experimental drug not yet approved in the US, can reduce "off-time" in people with Parkinson's disease (PD) who take levodopa therapy. The results appear in the March 11 online edition of Movement Disorders. Istradefylline is an adenosine receptor antagonist (A2A), a type of drug that works in a way that is different from levodopa. Several trials have examined whether it could help people with PD who experience fluctuations in the effectiveness of levodopa, which are called off-times.

This study led by Yoshikuni Mizuno, M.D., at the Kitasato University School of Medicine, recruited 373 people in Japan with PD movement symptoms ranging from mild to severe. Participants were on average 66 years old and experienced about six hours a day of off-time. They received either 20 mg of istradefylline, 40 mg of istradefylline or a placebo.

Results

  • Daily off-time was reduced by about one hour among participants who received either 20 mg/day or 40 mg/day of istradefylline. (The higher dose did not show a stronger effect.)
  • 12 of the 18 people who developed ICDs also experienced punding behaviors — that is, repetitive tasks such as sorting, organizing or using the Internet.
  • Among those taking istradefylline, the most common side effect was increased dyskinesias (involuntary movements); however, at neither dose level were dyskinesias considered troublesome.
  • Istradefylline was safe and generally well-tolerated.

What Does it Mean?

The findings of this new study support those of earlier studies showing that istradefylline may provide a modest benefit by reducing off-times for people with Parkinson's who take levodopa.

It is encouraging that istradefylline reduced offtime by, on average, about an hour a day, but discouraging that it increased dyskinesias, albeit not serious ones. The findings of this study also suggest that increasing the dosage of the drug does not enhance its modest benefit.

Istradefylline is one of several A2A antagonists being studied for PD. It was recently approved in Japan. Although studies in the US have found it to be safe, results on its effectiveness have been mixed. The modestly encouraging results of this study may put istradefylline back on track to becoming approved as a treatment option in the US.

Back to Contents for Summer 2013 News & Review