{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:44:31Z","timestamp":1780433071881,"version":"3.54.1"},"reference-count":19,"publisher":"Society for Neuroscience","issue":"14","license":[{"start":{"date-parts":[[2008,10,2]],"date-time":"2008-10-02T00:00:00Z","timestamp":1222905600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2008,4,2]]},"abstract":"<jats:p>Advances in viral gene therapy have opened new possibilities for treating a range of motor neuron diseases, but these have not yet been translated into clinically applicable therapies because of difficulties in delivery to susceptible\/damaged neurons, ambiguities in the identity of gene(s) implicated, and a paucity of means to quantify any physiological improvement. Most of these hurdles can be overcome by using the neuromuscular paralysis induced by botulinum neurotoxin type A (BoNT\/A) as a prototype disease. Furthermore, because human botulism, occasionally fatal, causes prolonged muscle disablement as a result of the intraneuronal persistence of the toxin's SNAP-25 (S25)-cleaving protease, development of a genetic approach could lead to a potential treatment for this debilitating disease. Adeno-associated viral delivery of a cleavage-resistant S25 gene (S25-R198T) to chromaffin cells<jats:italic>in vitro<\/jats:italic>yielded exocytotically active S25-R198T that diminished subsequent blockade by BoNT\/A of evoked catecholamine release. Evaluation<jats:italic>in vivo<\/jats:italic>, by administering this virus into rat spinal cord before injecting BoNT\/A, showed a decreased inhibition of acetylcholine release as reflected in elevated retention of neuromuscular transmission. A similar, although smaller, protection of synaptic transmission from the toxin was seen after peripherally injecting the therapeutic virus. Such therapy also curtailed nerve sprouting normally induced by BoNT\/A. This first demonstration of the utility of a DNA-based therapy for botulism paves the way for further advances in its treatment and for application to genetic disorders of motor neurons.<\/jats:p>","DOI":"10.1523\/jneurosci.5690-07.2008","type":"journal-article","created":{"date-parts":[[2008,4,2]],"date-time":"2008-04-02T16:34:29Z","timestamp":1207154069000},"page":"3683-3688","source":"Crossref","is-referenced-by-count":9,"title":["Adeno-Associated Virus Transfer of a Gene Encoding SNAP-25 Resistant to Botulinum Toxin A Attenuates Neuromuscular Paralysis Associated with Botulism"],"prefix":"10.1523","volume":"28","author":[{"given":"Arvind","family":"Raghunath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Perez-Branguli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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