Mitochondrial Biomarkers in Huntington's Disease

This investigator-initiated, single-site longitudinal study seeks to assess the utility of mitochondrial metabolomics -- panels of small molecules that affect mitochondrial function -- to diagnose pre-symptomatic, pre-manifest, and symptomatic Huntington's disease and serve as biomarkers for HD severity and progression. It also seeks to demonstrate that this novel biomarker in the blood has comparable value to the same analysis in spinal fluid. This research study involves 3-4 visits over 18 months. Forty volunteers with HD and 25 volunteers without HD will be included. Volunteers who have HD will have a physical examination and blood draw at each study visit. Some participants will also volunteer for optional lumbar puncture.

Inclusion criteria

• Age 20 to 85
• Montreal Cognitive Assessment score >10
• HD subjects had onset of HD symptoms after the age of 20
• HD subjects with Diagnostic Confidence Level (DCL) of 0-3 (pre-symptomatic or pre-manifest) must have at least 40 CAG repeats on one HTT allele
• HD subjects with Diagnostic Confidence Level (DCL) of 4 (manifest) must have at least 36 CAG repeats on one HTT allele
• Controls are asymptomatic without family history of HD or have <36 CAG repeats on both HTT alleles with family history of HD

Exclusion criteria

• HD subjects who did not already have genetic testing are excluded from this study
• Pregnancy or plans to become pregnant during the study
• Investigational drugs within 3 months of screening visit
• Alcohol or illicit drug abuse or dependence
• Other genetic or neurological disorders
• Other medical or psychiatric illness that in the investigator's judgement will prevent ability to tolerate or undergo study procedures
• For those volunteering for lumbar puncture (LP), bleeding disorders or excessive bleeding, anticoagulation, aspirin if unable to safely stop taking it at least 7 days prior to LP, other antiplatelet medications, inability to tolerate LP, allergy to local anesthetic or chlorhexidine, major lumbar spine deformity, low platelets or abnormal coagulation factors PT/APTT