A Study to Evaluate AB-1001 Striatal Administration in Adults With Early Manifest Huntington's Disease

This is an interventional treatment trial for Huntington Disease focused on measuring Huntington's Disease, Early Manifest Huntington's Disease, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases, Genetic Diseases, Inborn, Cognition Disorders, Neurocognitive Disorders, Gene Therapy, AAV (adeno-associated virus), Viral Vector, Cholesterol 24-Hydroxylase, CYP46A1, AB-1001 Read More

Inclusion Criteria:

• Male or Female subjects between ages 18 and 65 years (both inclusive) at time of consenting, able to provide Informed Consent and able to understand and comply with all study procedures.
• Documented genetic confirmation of pathological CAG expansion in the huntingtin gene ≥40.
• Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and a diagnostic classification level (DCL) of 4, or a DCL of 3 if present with cognitive impairment and clear evidence of disease progression.
• Striatal MRI volumes per hemisphere: Putamen ≥ 2.3 cm3 (per side); Caudate ≥ 1.7 cm3 (per side) on Screening MRI.
• All HD concomitant medications stable for at least 30 days prior to screening at the investigator's discretion.

Key Exclusion Criteria:

• Prior or ongoing medical condition, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, would impact subject's safety and compliance with the study procedures.
• Metastatic neoplasms within the five years prior to screening.
• Presence of clinically relevant immunologic, hematologic, hepatic, cardiac, or renal disease at the time of screening as per investigator's clinical judgment.
• Current untreated and unstable depressive disorder or a serious mood disorder requiring hospitalization.
• History of prior suicide attempt or imminent risk of self-harm based on investigator's judgment or with a "yes" answer on item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS).
• Patients with history of confirmed stroke, known intracranial neoplasms, vascular malformations, or intracranial hemorrhage.
• Subjects not deemed suitable for the surgical procedure as per the Neurosurgeon's judgment.
• Any history of gene therapy, cell transplantation or any other experimental brain surgery.
• Any RNA or DNA targeted HD specific investigational agents such as antisense oligonucleotides within 6 months prior to screening.
• Subjects unable to tolerate or unwilling to undergo multiple lumbar punctures.
• Participation in any clinical trial of an approved or non-approved investigational drug or intervention within 12 weeks or 5 half-lives whichever is longer prior to treatment.