Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

Polyzos, Aris; Holt, Amy; Brown, Christopher; Cosme, Celica; Wipf, Peter; Gomez-Marin, Alex; Castro, Maríadel R.; Ayala-Peña, Sylvette; McMurray, Cynthia T.

doi:10.1093/hmg/ddw051

Title: Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

Journal Article · Sun Feb 21 00:00:00 EST 2016 · Human Molecular Genetics

DOI:https://doi.org/10.1093/hmg/ddw051· OSTI ID:1379313

Polyzos, Aris ^[1]; Holt, Amy ^[1]; Brown, Christopher ^[2]; Cosme, Celica ^[2]; Wipf, Peter ^[3]; Gomez-Marin, Alex ^[4]; Castro, Maríadel R. ^[5]; Ayala-Peña, Sylvette ^[5]; McMurray, Cynthia T. ^[1]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States)
Univ. of Pittsburgh, PA (United States)
Consejo Superior de Investigaciones Cientificas (CSIC), Madrid (Spain)
Univ. of Puerto Rico, San Juan, PR (United States)

Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a graying phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1379313

Journal Information:: Human Molecular Genetics, Vol. 25, Issue 9; ISSN 0964-6906

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 35 works

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