Scientists optimize gene delivery system for treatment of Parkinson's
disease in rats
WESTPORT, Oct 12, 1999 (Reuters Health) - Insertion of a modified
adenovirus vector encoding the human tyrosine hydroxylase gene into a
"gene regulatory cassette" allows for directed, long-term and controlled
expression of the therapeutic gene in a rat model of Parkinson's
disease.
"Transposed to new generations of adenovirus vectors optimized for
minimal cytotoxicity and immunogenicity, this system should provide a
substantial advance toward the development of beneficial and safe
therapies for human neurodegenerative diseases," Dr. Olga Corti, of
Hopital de la Pitie Salpetriere in Paris, France, and multicenter
colleagues write in the October 12th issue of Proceedings of the
National Academy of Sciences.
The scientists injected the vector directly into the
dopamine-depleted striatum in a rat model of Parkinson's disease. They
demonstrated targeted expression of human tyrosine hydroxylase "...in
numerous striatal cells," with transgene expression measurable in most
of them for at least 17 weeks.
The inclusion of a tetracycline-sensitive gene regulatory system in
the vector allowed the researchers to maintain exogenous control over
transgene expression with the use of doxycycline, a tetracycline analog.
However, the team notes that use of this system to deliver human
tyrosine hydroxylase to the dopamine-depleted rats did not result in
functional recovery. In fact, striatal levels of dopa, dopamine and
dopamine metabolites were not higher in rats injected with the
transgene-encoding vector than in those administered a control vector,
despite high levels of transgene expression.
The authors conclude that co-transfer of other factors associated
with dopamine biosynthesis may be needed for gene therapy to be
successful in the treatment of Parkinson's disease in humans,
Proc Natl Acad Sci USA 1999;96:12120-12125.
1999 Reuters Limited.
--
Judith Richards, London, Ontario, Canada
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