PDR-001 delivered into the brain to remove harmful alpha-synuclein in early Parkinson's

A Study on the Safety, Tolerability, and Efficacy of PDR-001 Injection for Bilateral Stereotactic Subthalamic Nucleus (STN) Clearance of α-synuclein

This trial will try PDR-001 (a peptide packaged in AAV9) injected into a brain target to remove toxic alpha-synuclein in people aged 40–65 with early Parkinson's disease.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 40 Years to 65 Years
• Sex: All
• Sponsor: Ruijin Hospital (other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07157345 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study delivers tat-βsyn-deg (PDR-001) packaged in AAV9 by bilateral stereotaxic injection into the subthalamic nucleus to reduce pathological α-synuclein. The primary focus is safety and target engagement in a small cohort of patients with early-stage primary Parkinson's disease. Eligible participants are ages 40–65 with disease duration ≤5 years and Hoehn & Yahr stage ≤2, while those with atypical parkinsonism, prior intracranial surgery, or structural brain abnormalities are excluded. The trial is conducted at a single center (Ruijin Hospital, Shanghai) with surgical delivery and scheduled follow-up visits.

Who should consider this trial

Good fit: Ideal candidates are people with clinically confirmed early primary Parkinson's disease, aged 40–65, with disease duration of five years or less and Hoehn & Yahr stage 2 or lower who are medically eligible for stereotactic brain injection.

Not a fit: Patients with atypical or secondary parkinsonism, advanced disease, prior intracranial procedures, structural brain abnormalities, or contraindications to neurosurgery are unlikely to benefit or be eligible for participation.

Why it matters

Potential benefit: If successful, this approach could lower toxic α-synuclein in targeted brain regions and potentially slow or halt progression of motor decline by protecting dopaminergic neurons.

How similar studies have performed: Preclinical animal studies reported regional reduction of α-synuclein and some neuroprotection, but human safety and efficacy data for this approach are currently lacking.

Eligibility criteria

Inclusion Criteria:

To be eligible for inclusion in this clinical study, all of the following criteria must be met:

1. Clinically confirmed diagnosis of primary PD (in accordance with the 2016 Chinese Diagnostic Criteria for Parkinson's Disease or the 2015 MDS Clinical Diagnostic Criteria for primary PD);
2. Age 40-65 years (inclusive) at screening, either sex;
3. Disease duration ≤ 5 years;
4. Hoehn \& Yahr stage ≤ 2 in the "off" state.

Exclusion Criteria:

Exclusion Criteria

1. Atypical or secondary parkinsonian syndromes (e.g., Parkinson-plus syndromes, hereditary parkinsonism, drug-induced parkinsonism, etc.).
2. Contra-indications to surgery, or any prior intracranial procedure such as deep-brain stimulation, pallidotomy, or other extrapyramidal surgery, or any other neurosurgical intervention deemed by the investigator to interfere with study participation.
3. Previous neuroimaging revealing structural brain abnormalities, cerebral vascular malformations, intracranial tumors, risk of intracranial hemorrhage, traumatic brain injury, or other significant findings.
4. Mini-Mental State Examination (MMSE) score \< 24.
5. Patient Health Questionnaire-9 (PHQ-9) score ≥ 16.
6. Abnormal hepatic or renal function: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 1.5 × upper limit of normal (ULN), or serum creatinine (Cr) \> 1.5 × ULN.
7. Coagulation disorders or current use of anticoagulants.
8. Positive screening for infectious diseases:

   * Hepatitis B surface antigen (HBsAg) or Hepatitis B virus DNA (HBV-DNA) positive;
   * Hepatitis C virus RNA (HCV-RNA) positive;
   * Human immunodeficiency virus (HIV) positive;
   * Positive syphilis serology.
9. Currently receiving antiviral therapy for hepatitis B or C.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin hospital — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Yi Zhang

Conditions: Parkinson Disease, PDR-001, Parkinson disease