Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington Disease

Open to people ages 25-65

• First 4 subjects in Cohort 1: early manifest HD (Stage 2). All remaining subjects in

Cohort 1 and all subjects in Cohort 2: early manifest HD (Stages 1 and 2).

• HTT gene expansion testing with the presence of ≥44 CAG repeats.
• Striatal MRI volume requirements per hemisphere: Putamen ≥2.5 cm3 (per side); Caudate ≥2.0 cm3 (per side)
• All HD concomitant medications stable for 3 months prior to Screening.

• Receipt of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
• Participation in an investigational trial or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation, etc.) within 60 days prior to Screening or anytime over the duration of this study.
• Presence of an implanted deep brain stimulation device.
• Any history of gene therapy, RNA or DNA targeted HD specific investigational agents, such as antisense oligonucleotides (ASO), cell transplantation or any other experimental brain surgery.
• Any contraindication to lumbar puncture or 3.0 Tesla MRI as per local guidelines.
• Brain and spinal pathology that may interfere with CSF homeostasis and circulation, increased intracranial pressure (including presence of a shunt for the drainage of CSF or an implanted CNS catheter), malformations and/or tumors.
• Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
• Current use of medications that could improve or worsen chorea or other HD movements including typical neuroleptics, tetrabenazine and deutetrabenazine.