A Pre-Cellular Therapy Observational Study in Early Huntington's Disease

A Pre-Cellular Therapy Observational Study in Early Huntington's Disease

This observational study will establish a clinical baseline and measure changes over time in movement, thinking, behavior, brain imaging, blood and spinal fluid markers in subjects with early stage Huntington's disease. Participants enrolled in this study may be eligible to participate in a future planned study of stem cell therapy for Huntington's Disease (HD).

In-person study visits occur at screening, baseline, and every 6 months thereafter for a minimum of 12 months, with interim phone call assessments.

In PRE-CELL the investigators propose to enroll a cohort of early-stage HD patients in a prospective observational study designed to characterize clinical, neuro-imaging, laboratory and biomarker correlates of disease progression over 12-18 months. Subjects who complete a minimum of 12 months' participation in this trial will be candidates for enrollment in the future planned Phase 1 trial of intrastriatal delivery of mesenchymal stem cell (MSC)/Brain-derived neurotrophic factor (BDNF).

Inclusion Criteria:

• Men or women age 18 and older, English speaking, able to give informed consent and comply with study procedures.
• HD diagnosis confirmed with genetic testing demonstrating CAG trinucleotide repeat length (CAGn) greater than 37
• Early stage HD with Total Functional Capacity (TFC) score of 9-13
• Demonstrable motor signs with a Unified Huntington's Disease Rating Scale (UHDRS) diagnostic confidence level of 4
• Must have a caregiver or informant able to give feedback about the participant and willing to report observations about subject on standardized forms.
• Subjects of child bearing potential must agree to adequate birth control measures including intrauterine device, hormone therapy, hormone rings or barrier methods including foams/gels AND condoms.

Exclusion Criteria:

• Very early disease without demonstrable motor signs (diagnostic confidence level < 4)
• Significant cognitive impairment or dementia as defined by Montreal Cognitive Assessment (MoCA) score < 12.
• Moderate or advanced disease with TFC < 9
• Concurrent active unstable psychiatric disease including history of suicide attempts within the last year, major personality or psychiatric disorders.
• History of concurrent serious medical illness such as HIV or current anti-retroviral treatment, cancer, major cardiac, pulmonary, immunological or other organ disease.
• History of coagulopathy, bleeding disorder, or concurrent use of blood thinners.
• History of brain tumor, serious traumatic brain injury with coma, or history of brain surgery.
• Any comorbid condition that presents an unacceptable health risk to the patient in the investigator's view
• Clinically significant laboratory test abnormalities, including full blood count, chemistry panel, liver function tests, Prothrombin time/international normalized ratio (PT/INR), lipid panel, electrocardiogram (EKG), or chest x-ray as judged by the investigator.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with safety or adherence to study requirements.
• History or documentation of contraindication for MRI brain scan, including the presence of pacemaker, neurostimulator, aneurysm clips, artificial heart valves, cochlear implants, metal fragments in the eyes, orbits or skin or any other known contraindication to MRI.
• Any significant MRI brain scan findings other than those characteristic of HD.
• Any contraindications to surgery or to the use of general anesthesia, including allergy.
• History of use of any investigational agent within 60 days prior to enrollment
• History of current or previous gene therapy or stem cell therapy.
• History of previous or current treatment with cytokines
• History of sensitivity to ganciclovir.
• Pregnant and/or lactating women