Gene Therapy Used to Prevent Parkinson’s Disease in Primates

In February, the The Journal of Neuroscience published the results of efforts to use gene therapy to boost levels of a protein that is believed to preserve brain cells and may someday form the basis of a treatment for Parkinson’s Disease.

The protein is glial cell line-derived neurotrophic factor (GDNF). It has been tested in human beings but so far with mixed results. A trial of GDNF therapy in human beings had to be stopped in October 2004 due to safety concerns. In that trial, GDNF was introduced directly into the brain of 34 patients. Four of the patients developed antibodies against GDNF within six months of the trial. In conjunction with research on primates that found the brain cells of the animals began to break down after the GDNF treatment, the human trial was stopped.

An earlier smaller-scale trial of GDNF in the UK showed improvement in Parkinson’s patients given GDNF, and there’s debate over whether the difference in the two studies is related to the effect of GDNF or possible differences in the protocols of the two studies.

A couple teams of international researchers, however, recently published their results of another method of delivering GDNF — using gene therapy to force the bodies of affected animals to produce GDNF. There are likely to be a number of advantages to this over the current practice of simply introducing it directly into the brain, including producing GDNF at levels that are likely to be safer for the patient.

In research sponsored by Lund University in Lund, Sweden; the University of Cambridge; and the McKnight Brain Institute and the Genetics Institute of the University of Florida, researchers used gene therapy to insert copies of a gene responsible for creating GDNF in the front part of the brain into monkeys. Researchers then induced an animal model of Parkinson’s in the monkeys by exposing them to a drug that destroys dopamine producing cells.

After 17 weeks, monkeys that had received the gene therapy not only had a significantly higher ability to perform tasks than a control group that did not receive the gene therapy, but analysis of brain tissue showed the GDNF had a protective affect on the dopamine producing cells in the experimental group of monkeys.

Dr. Nicholas Mzyczka, of the University of Florida’s College of Medicine, said in a press release announcing the results,

The simplest question we’re asking is, “Does any particular combination of proteins prevent or accelerate degeneration of the neurons?” For some time Dr. [Ron] Mandel has been working on the idea of introducing a vector into the brain that would express GDNF. What they’ve found is that if you get low-level expression, you can prevent cell death in a part of the brain called the substantial nigra. That’s been shown before in rodent models, but it’s encouraging to see data that it works in higher animals like monkeys.

In the same press release, Mandel said of the current status of GDNF as a possible treatment for Parkinson’s,

Our strategy is a neuroprotective concept and would only be amenable for early stage patients to keep a good quality of life. It would be a huge change in the way treatment is done. We know the GDNF protects the neurons in primates from the model that we use, so that’s good. We know we can use very low doses that are still effective, so that’s good. But we need a safety net. Once we turn it on, it’s on for life. So we have to control it, and we’re working on this as we speak. But it’s not ready for clinical trials.


Gene therapy for Parkinson’s Disease moves forward in animals. Press Release, University of Florida Health Science Center, February 10, 2005.

Parkinson’s trial halted. Helen Pearson, Nature, October 5, 2004.

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