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Potential biomarkers to follow the progression and treatment response of Huntington’s disease
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2016
- Publisher :
- Rockefeller University Press, 2016.
-
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.<br />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.
- 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
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 213
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....b5bbe71c2e3d9712031752758c899d0c