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

Participants will receive totally 8 intravenous injections of ER2001 on the first day of the study, after 2 weeks they will receive 6 injections at weekly intervals, followed by 1 injections at 6 weeks interval. The treatment period of 14 weeks will be followed by an observation phase of 84 days . A modified 3 plus 3 dose-escalation design will be employed with escalating rules set according to the incidence of dose-limiting toxicity (DLT). The first cohort of 1-6 participants will receive a low dose. After safety analysis the next cohort of 3-6 will received a higher dose. Planned doses for increase in subsequent cohorts are 0.04, 0.08, 0.16, and 0.32 mg/kg. Decision to proceed to the next higher dose cohort will be based upon a safety review of the included participants. Treatment will continue until intolerable toxicity or as per patient preference.

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Current active psychosis, confusional state, or violent behavior.
• 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.
• 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.)
• Patients with HIV, Treponema pallidum, Hepatitis B, or Hepatitis C infection.
• Need to take antiretroviral drugs, including antiretroviral drugs as preventive treatment.
• 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.
• 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.
• 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.
• Unable or unsafe to perform lumbar puncture on the patient.
• In the Investigator's judgment, that Parkinson's disease, multiple system atrophy and other dystonia diseases may be combined.
• Patients who are hypersensitive to any ingredients in the formulation of ER2001.
• 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.
• Concurrent or planned concurrent participation in any interventional clinical study, including explicit pharmacological and non-pharmacological interventions. Observational studies are acceptable.
• 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.