TY - JOUR
T1 - Cystamine and intrabody co-treatment confers additional benefits in a fly model of Huntington's disease
AU - Bortvedt, S. F.
AU - McLear, J. A.
AU - Messer, A.
AU - Ahern-Rindell, A. J.
AU - Wolfgang, W. J.
PY - 2010/10
Y1 - 2010/10
N2 - Huntington's disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HTT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD model cystamine, or expressing a transgene encoding the anti-htt intracellular antibody (intrabody) C4-scFv in the nervous system, demonstrated therapeutic potential, but suppression of pathology was incomplete. We hypothesized that a combinatorial approach entailing drug and intrabody administration could enhance rescue of HD pathology in flies and that timing of treatment would affect outcomes. Feeding cystamine to adult HD flies expressing the intrabody resulted in a significant, additional rescue of photoreceptor neurodegeneration, but no additional benefit in longevity. Feeding cystamine during both larval and adult stages produced the converse result: longevity was significantly improved, but increased photoreceptor survival was not. We conclude that cystamine-intrabody combination therapies can be effective, reducing neurodegeneration and prolonging survival, depending on administration protocols.
AB - Huntington's disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HTT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD model cystamine, or expressing a transgene encoding the anti-htt intracellular antibody (intrabody) C4-scFv in the nervous system, demonstrated therapeutic potential, but suppression of pathology was incomplete. We hypothesized that a combinatorial approach entailing drug and intrabody administration could enhance rescue of HD pathology in flies and that timing of treatment would affect outcomes. Feeding cystamine to adult HD flies expressing the intrabody resulted in a significant, additional rescue of photoreceptor neurodegeneration, but no additional benefit in longevity. Feeding cystamine during both larval and adult stages produced the converse result: longevity was significantly improved, but increased photoreceptor survival was not. We conclude that cystamine-intrabody combination therapies can be effective, reducing neurodegeneration and prolonging survival, depending on administration protocols.
KW - Combinatorial therapy
KW - Neurodegenerative disease
KW - Polyglutamine
KW - ScFv
UR - http://www.scopus.com/inward/record.url?scp=77955843583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955843583&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2010.04.007
DO - 10.1016/j.nbd.2010.04.007
M3 - Article
C2 - 20399860
AN - SCOPUS:77955843583
SN - 0969-9961
VL - 40
SP - 130
EP - 134
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -