05 Oct 2000

A two-gene therapy strategy prevents the death of dopamine neurons and preserves their function, according to a study by Jorg Schulz and colleagues at the University of Tubingen in Germany. The study was carried out in an MPTP mouse model (the toxin MPTP selectively damages and kills the neurons that are vulnerable in Parkinson's). Initially, the researchers, using an adenovirus vector, delivered the gene for X-chomosome-linked inhibitor of apoptosis (XIAP), which blocks caspases involved in neuronal death. The gene prevented the neurons from dying, but the cells lost their nerve projections and stopped delivering dopamine to the striatum, an area that is essential for normal movement. The researchers then tried treating a second set of mice with both XIAP and a growth-promoting gene called glial cell line-derived neurotrophic factor (GDNF). In these animals, the neurons not only survived but resumed their dopamine-delivering function. "The results suggest," said Schulz, "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." Much work remains to be done, however, before this promising strategy can be tried in human patients. A better adenoviral vector is needed both to reduce the minor inflammation at the point of injection, and to allow the therapeutic genes to be expressed longer than the current three to eight weeks, according to Schulz. The study was reported last week at the American Neurological Association meeting in Boston, and will be published in Journal of Neuroscience.—Hakon Heimer