 |
 |
------------------------------------------------------------------------ Gene Transfer Prevents Onset Of Parkinson's Disease In Rat Model ------------------------------------------------------------------------ WESTPORT, Aug 05 (Reuters) - Intrastriatal transfer of the gene for glial-cell-line-derived neurotrophic factor (GDNF) via an adenoviral vector can prevent nerve cell degeneration characteristic of Parkinson's disease in rats, according to a report in Proceedings of the National Academy of Sciences for August 5. Because of GDNF's "...protective and restorative effects on the nigro-striatal dopaminergic system," the trophic factor is a potential therapy for Parkinson's disease. However, since the factor cannot cross the blood-brain barrier, its use for this indication has been limited. Dr. Alicia Bilang-Bleuel of the Centre National de la Recherche Scientifique in Paris and colleagues there and at other centers in France developed an adenoviral vector encoding the gene for GDNF. After injecting the vector into rat striatum, the researchers observed a large increase in the production of GDNF in rat brains, indicating the gene transfer had been successful. The GDNF produced in these mice was also biologically active, as "...it increased the survival and differentiation of [dopaminergic] neurons in vitro." Next, Dr. Bilang-Bleuel and colleagues tested the GDNF-carrying adenoviral vector in rats with a progressive lesion form of Parkinson's disease. They injected the animals with the vector 6 days prior to administering 6-hydroxydopamine, which initiates dopaminergic neuron degeneration in this rat model. The GDNF vector protected mesencephalic nigral dopamine neurons against degeneration, and increased survival of the neurons for up to 3 weeks after administration of the vector. Moreover, this protection was associated with a significant difference in motor function between GDNF rats and control rats with progressive Parkinson's lesions. Unfortunately, the vector itself had toxic effects. The French researchers report "...the size of the striatum was slightly reduced..." in animals that received either a GDNF-carrying vector or a control vector. Moreover, almost 40% of the dopaminergic neurons were destroyed in animals that were administered the control vector but not the Parkinson's disease-inducing injection of 6-hydroxydopamine. Regardless, the findings indicate that gene transfer of GDNF "...might be of therapeutic value for Parkinson's disease [in humans]." Proc Natl Acad Sci USA 1997;94:8818-8823. Westport Newsroom 203 319 2700 Copyright 1997 Reuters Limited. <http://www.reutershealth.com/news/docs/199708/19970805scc.html> ------------------------------------------------------------------------ [log in to unmask]