The Safety and Tolerability Study With ER2001 Intravenous Injection in Adults With Early Manifest Huntington's Disease

Prior treatment

• History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening.
• Need to take antiretroviral drugs, including antiretroviral drugs as preventive treatment.
• Any history of gene therapy, RNA or DNA investigational agents, such as antisense oligonucleotides (ASO), cell transplantation or any other experimental brain surgery.
• Treatment with investigational therapy within 4 weeks prior to screening or 5 drug elimination half-lives of investigational therapy, whichever is longer.
• Concurrent or planned concurrent participation in any interventional clinical study, including explicit pharmacological and non-pharmacological interventions. Observational studies are acceptable.

Other illness

• Bleeding tendency or history of coagulation disorder; As long as the investigator confirms that there is no evidence of bleeding tendency or coagulation dysfunction at present.
• Patients with HIV, Treponema pallidum, Hepatitis B, or Hepatitis C infection.
• In the Investigator's judgment, that Parkinson's disease, multiple system atrophy and other dystonia diseases may be combined.
• Malignancy within 5 years of screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.

Lab values

• ECG with corrected QT interval (QTc) \> 480 ms and/or indication of uncontrolled cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction,congestive heart failure, electrolyte disturbances, etc.)
• Current or recurrent disease, infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a subject's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule.
• Any serious medical condition or clinically significant laboratory, vital signs, or abnormalities at screening that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study.

Other

• Current active psychosis, confusional state, or violent behavior.
• Clinical diagnosis of chronic migraines.
• Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter.
• Preexisting structural brain lesions (such as tumor, arteriovenous malformation) as assessed by a centrally read MRI scan during the screening period.
• Unable or unsafe to perform lumbar puncture on the patient.
• Patients who are hypersensitive to any ingredients in the formulation of ER2001.

• Patient has documented ability to understand the written study informed consent forms (ICFs) at the time of screening and has provided signed written informed consent prior to any study procedures.
• 25 Years to 55 Years. Gender is not limited.
• 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.
• HTT gene expansion testing with the presence of ≥40 CAG repeats.
• Ability to undergo and tolerate MRI scans.
• Ability to undergo and tolerate lumbar puncture.
• All HD medications given for motor, behavioral, and cognitive symptoms have been stable for 3 months prior to Screening.
• Other concomitant medications have been stable for 1 month prior to Screening.
• organ function measured prior to administration of study treatment.
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential. Male patients must use a condom during treatment and for 6 months after the last dose of ER2001 when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.