Gene Therapy Offers Hope to Sufferers of Parkinson's Disease ; HOME

Jun 22, 02:06 AM

Current Headlines: By Steve Connor

The first gene-therapy trial for treating Parkinson's disease has resulted in a significant improvement in all the patients who took part, with none suffering any side-effects, it was announced yesterday.

Doctors believe the trial marks a milestone in the treatment of one of the most common neurodegenera-tive disorders of elderly people for which there is no effective cure.

The phase 1 clinical trial, the first in a three-stage process, was designed to test the safety of the technique but the apparent benefits of the treatment to the 12 patients who took part was clear up to a year after they were treated.

Not only did the patients improve in terms of being able to control the movements of their muscles, brain scans also showed that there were real improvements to the nerve activity within the central nervous system.

Parkinson's disease affects about one in every 500 people, and there are about 120,000 patients in Britain, with 10,000 people newly diagnosed with the condition each year. Although drugs can alleviate symptoms, there is no treatment that can stop the progression of the disease.

The latest findings, published in The Lancet, are the first to suggest that injecting genes into regions of the brain that are affected by Parkinson's may arrest at least some of the severely debilitating symptoms.

"These exciting results need to be validated in a larger trial," said Michael Kaplitt, a neurosurgeon at the Weill Cornell Medical Centre in New York and a member of the team that conducted the research. "We believe this is a milestone, not only for the treatment of Parkinson's, but for the use of gene-based therapies against neurological conditions generally."

Parkinson's results in loss of nerve cells in a region of the brain called the substantia nigra. These cells are responsible for producing dopamine, a vital chemical messenger in the brain that helps to control muscle movements. However, another problem with Parkinsonism is the underproduction of a second chemical messenger called Gaba which inhibits nerve transmission and "calms" excessive nerve activity. Dr Kaplitt and his colleagues targeted this problem by injecting a gene called glutamic acid decarboxylase into the subthalamic region of the brain.

"Our hope was that with a single operation to this single site, we could boost Gaba production and thereby normalise the function of the entire circuit," Dr Kaplitt said.

The scientists genetically modified a virus that had been rendered harmless to carry the human gene into the brain cells. They injected only one side of the brain and used this to compare the effects of the therapy with the untreated hemisphere.

Standard methods of monitoring Parkinson's patients showed they fared better as a result of the treatment, with a 25-30 per cent improvement when they were not talking their usual medication, and a 40-65 per cent improvement when they were talking their drugs.

How doctors carried out first gene therapy on the brain

Patients with Parkinson's disease were injected with virus containing gene for vital brain chemical to treat symptoms

PARKINSON'S DISEASE

Loss of nerve cells in the substantia nigra region of the brain causes fall in level of dopamine, a key chemical messenger that helps to coordinate movement. The result is Parkinsonism

GENE THERAPY

1 Adeno-associated virus (AAV) is deactivated to render it harmless by removing key genes Deactivated virus

2 Then, a gene for human glutamic acid decarboxylase (GAD) is inserted into the genetic material of AAV Modified virus

3 The virus is injected into the subthalamic nucleus region of the brain

4 The virus carries the GAD gene into the human nerve cell which starts to produce the GAD protein. GAD results in an increase in the level of a chemical messenger in the brain called GABA, which is a nerve inhibitor that helps to calm excessive nerve activity in patients with Parkinson's

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