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Gene Therapy Rescues Brain Cells In Parkinson's Model

Date:
October 19, 2000
Source:
American Neurological Association
Summary:
A gene therapy "cocktail" can successfully prevent the destruction of critical brain cells in an animal model of Parkinson's disease, according to a study presented at the American Neurological Association's 125th annual meeting, October 15 through 18 in Boston.

Boston, MA -- A gene therapy "cocktail" can successfully prevent the destruction of critical brain cells in an animal model of Parkinson's disease, according to a study presented at the American Neurological Association's 125th annual meeting, October 15 through 18 in Boston.

Researchers from the University of Tubingen in Germany reported that they were able to prevent the death of dopamine neurons, which are selectively destroyed in the disorder, by simultaneously interfering with "executioner" molecules called caspases and nourishing brain cells with molecules called growth factors.

"We combined neuroprotective and neurorestorative strategies which acted in synergy, whereas both treatments on their own were only partially protective," said Jorg B. Schulz, MD, lead author of the report. "The results suggest that for the treatment of neurodegenerative diseases, and Parkinson's disease in particular, combinations of treatment strategies that interfere with different pathways may be superior."

Parkinson's disease afflicts patients with symptoms such as tremor when at rest, muscle rigidity, and slowness of movement.

The direct cause of Parkinson's disease is the progressive death of nerve cells in an area of the brain called the substantia nigra. These cells produce a chemical called dopamine that helps direct normal movement and activity. Scientists have not determined why these particular cells die, but without dopamine, the activity of other, related brain areas can be substantially altered.

Therapy with the drug levodopa and some surgical interventions can temporarily diminish symptoms of the disease. However, they cannot replace the lost brain cells, nor can they stop the progression of the disease.

Gene therapy represents one hope for preventing the loss of the dopamine-producing neurons. Schulz and his colleagues hypothesized that if they could interfere with a process called apoptosis, or programmed cell death, they might be able to rescue the dopamine neurons. They focused their effort on a group of molecules called caspases, which help to carry out apoptosis.

Their experimental approach was to insert the gene for a caspase inhibitor into the genetic material of a benign virus. This virus was then surgically injected into the brain, where it incorporated its genetic material into the chromosomes of the dopamine neurons. The neurons did the rest, producing caspase inhibiting proteins from the foreign gene code.

The caspase-fighting genes did was what was expected of them--they prevented the cells in the substantia nigra from dying. However, the cells lost their nerve projections and no longer delivered dopamine to areas of the brain that depend on the chemical, in particular the striatum, an area that is essential for normal movement.

In a second set of mice, the researchers added a gene for a molecule called a growth factor, which is known to nourish and rejuvenate neurons. The "cocktail" approach saved nearly all the dopamine neurons, as well as preserving the critical function of delivering dopamine to the striatum.

According to Schulz, the results should spur continued research into ways of safely delivering caspase-inhibitors--whether by traditional systemic routes or by gene therapy--to the brain in disorders that appear to involve apoptosis. In addition to Parkinson's, this includes stroke and head trauma.

"For slowly progressing neurodegenerative diseases such as Parkinson's disease, gene transfer methods that can target specific neuronal populations may be superior to systemic treatment and should be developed since they may prevent unwanted side effects of caspase inhibition," said Schulz.


Story Source:

The above story is based on materials provided by American Neurological Association. Note: Materials may be edited for content and length.


Cite This Page:

American Neurological Association. "Gene Therapy Rescues Brain Cells In Parkinson's Model." ScienceDaily. ScienceDaily, 19 October 2000. <www.sciencedaily.com/releases/2000/10/001018220700.htm>.
American Neurological Association. (2000, October 19). Gene Therapy Rescues Brain Cells In Parkinson's Model. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2000/10/001018220700.htm
American Neurological Association. "Gene Therapy Rescues Brain Cells In Parkinson's Model." ScienceDaily. www.sciencedaily.com/releases/2000/10/001018220700.htm (accessed October 21, 2014).

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