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One of the problems with traditional drug treatment for Parkinson’s disease is that the medicines lose effectiveness over time. Levadopa, for example, restores levels of dopamine, a chemical messenger lost in patients with the disorder. The drug can work for years, but ultimately triggers serious side effects, including tremors, muscle spasms, and uncontrolled flailing of the arms and legs.

In the new trial, reported today in the journal Science Translational Medicine, Bechir Jarraya and colleagues at the Molecular Imaging Research Center in Fontenay-aux-Roses, France, mimicked Parkinson’s in monkeys by giving them a neurotoxin that causes movement problems characteristic of the disorder. The researchers then injected three genes involved in dopamine production into the brains of the monkeys, as well as specially designed probes to measure dopamine levels in the brain, monitoring the animals for up to three and a half years. The gene therapy restored concentrations of dopamine in the brain, corrected movement problems, and prevented dyskinesias–without any severe adverse side effects. An early stage human clinical trial using the same dopamine gene therapy approach is now underway.

According to an article on the NatureNews website:

This success in monkeys paves the way for future studies in humans, says Palfi, who reported his animal results today in the journal Science Translational Medicine1. “This is the exact situation that we will face in the clinic,” he says. Palfi’s team has already tested two different doses of the three-gene-containing virus in six human patients, and is now investigating an intermediate dose that matches that used in the monkeys, with corrections for brain size. Once the researchers find the optimal dose, they plan to move the experimental treatment into Phase II trials, Palfi says.

…Palfi’s technique is not the only gene therapy currently being pursued for Parkinson’s disease. Some researchers are delivering genes that provide growth factors to halt the death of dopamine-producing neurons. Others are introducing genes that inhibit the excessive neural activity associated with Parkinson’s disease in the same way as the surgical process known as deep-brain stimulation. And yet others are focusing on single genes – rather than all three – with a role in dopamine synthesis.

But Palfi’s team is the first to deliver all three of the dopamine genes in a single viral vector in primates. This approach aims to eliminate the need for L-DOPA and its associated side effects. But the technique would mean that clinicians would no longer be able to fine-tune the levels of dopamine in the brain to meet the needs of the patient, notes Jamie Eberling, associate director of research programmes at the Michael J. Fox Foundation for Parkinson’s Research in New York City.

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Tagged: Biomedicine, gene therapy, dopamine

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