1. Potential biomarkers to follow the progression and treatment response of Huntington’s disease
- Author
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Blair R. Leavitt, Mehrdad Shamloo, Amit Joshi, Daria Mochly-Rosen, Xin Qi, Marie Helene Disatnik, and Nay L. Saw
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Huntingtin ,Immunology ,Disease ,Biology ,Bioinformatics ,DNA, Mitochondrial ,Article ,Mice ,Protein Aggregates ,03 medical and health sciences ,0302 clinical medicine ,Huntington's disease ,Biopsy ,medicine ,Huntingtin Protein ,Animals ,Humans ,Immunology and Allergy ,Muscle, Skeletal ,Research Articles ,Genetic testing ,Inflammation ,Aldehydes ,Behavior, Animal ,medicine.diagnostic_test ,Neurotoxicity ,Case-control study ,Brain ,medicine.disease ,Body Fluids ,Mitochondria ,3. Good health ,Huntington Disease ,Phenotype ,030104 developmental biology ,Case-Control Studies ,Disease Progression ,Oxidation-Reduction ,Biomarkers ,030217 neurology & neurosurgery ,DNA Damage - Abstract
Disatnik et al. identify mitochondrial DNA levels, 8-OHdG, and inflammation factors as potential peripheral biomarkers to follow progression and treatment response of Huntington’s disease., Huntington’s disease (HD) is a rare genetic disease caused by expanded polyglutamine repeats in the huntingtin protein resulting in selective neuronal loss. 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.
- Published
- 2016