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Although genetic testing readily identifies those who will be affected, current pharmacological treatments do not prevent or slow down disease progression. A major challenge is the slow clinical progression and the inability to biopsy the affected tissue, the brain, making it difficult to design short and effective proof of concept clinical trials to assess treatment benefit. In this study, we focus on identifying peripheral biomarkers that correlate with the progression of the disease and treatment benefit. We recently developed an inhibitor of pathological mitochondrial fragmentation, P110, to inhibit neurotoxicity in HD. Changes in levels of mitochondrial DNA (mtDNA) and inflammation markers in plasma, a product of DNA oxidation in urine, mutant huntingtin aggregates, and 4-hydroxynonenal adducts in muscle and skin tissues were all noted in HD R6\/2 mice relative to wild-type mice. Importantly, P110 treatment effectively reduced the levels of these biomarkers. Finally, abnormal levels of mtDNA were also found in plasma of HD patients relative to control subjects. Therefore, we identified several potential peripheral biomarkers as candidates to assess HD progression and the benefit of intervention for future clinical trials.<\/jats:p>","DOI":"10.1084\/jem.20160776","type":"journal-article","created":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T15:07:38Z","timestamp":1478531258000},"page":"2655-2669","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Potential biomarkers to follow the progression and treatment response of Huntington\u2019s disease"],"prefix":"10.1084","volume":"213","author":[{"given":"Marie-H\u00e9l\u00e8ne","family":"Disatnik","sequence":"first","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit U.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3676-6580","authenticated-orcid":false,"given":"Nay L.","family":"Saw","sequence":"additional","affiliation":[{"name":"Behavioral and Functional Neuroscience Laboratory, Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4404-1755","authenticated-orcid":false,"given":"Mehrdad","family":"Shamloo","sequence":"additional","affiliation":[{"name":"Behavioral and Functional Neuroscience Laboratory, Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R.","family":"Leavitt","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9578-3890","authenticated-orcid":false,"given":"Xin","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Mochly-Rosen","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2016,11,7]]},"reference":[{"key":"2023072608495037200_bib1","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1016\/j.drudis.2014.03.002","article-title":"Biomarker development for Huntington\u2019s disease","volume":"19","author":"Andre","year":"2014","journal-title":"Drug Discov. 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