Testing if PDR-001 Can Safely and Effectively Remove Harmful Brain Protein in Parkinson's Disease

NCT07157345 | Recruiting Phase 1

• 1 other identifier: V1.0/2025-07-06
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's disease (PD) poses a severe threat to human health, and its incidence is rising year by year. Current therapeutic options are limited by significant shortcomings. Pathological aggregation of α-synuclein and the consequent death of dopaminergic neurons are the primary drivers of PD pathogenesis. While siRNA-mediated knockdown of α-synuclein can offer some protection to dopaminergic neurons, its clinical utility is hampered by low cellular uptake, off-target effects, and transient activity. These drawbacks underscore the urgent need for novel strategies that can efficiently and specifically degrade α-synuclein to delay or even halt PD progression. Our prior work identified tat-βsyn-deg (PDR-001), a three-segment peptide that selectively targets α-synuclein. When packaged into AAV9 capsids and delivered via bilateral stereotaxic injection into the subthalamic nucleus, this peptide effectively reduces α-synuclein within the target region. Pre-clinical studies in both human-α-synuclein-expressing mice and non-human primate models of PD have demonstrated robust α-synuclein clearance and marked improvements in motor deficits (see Research Foundation). The present project will advance PDR-001 into first-in-human studies to evaluate safety and explore preliminary efficacy. Unlike conventional symptomatic therapies, this approach targets the root cause of PD, setting the stage for disease-modifying treatment. Successful translation would establish a new therapeutic paradigm capable of slowing or preventing PD progression.

Conditions

Parkinson Disease (PD)

Keywords

PDR-001; Parkinson disease

Outcome Measures

Primary Outcomes (3)

• PDR-001 treatment-related adverse events as assessed by CTCAE v5.0

  CTCAE 5.0 records the severity of adverse events, which is divided into grades 1 to 5

  From enrollment to the end of treatment at 52 weeks

• Titer levels of capsid neutralizing antibodies and binding antibodies against recombinant adeno-associated virus (rAAV) in serum

  Record the titer changes before and after treatment

  From enrollment to the end of treatment at 52 weeks

• Titer of rAAV vectors in whole blood

  Record the titer changes before and after treatment

  From enrollment to the end of treatment at 52 weeks

Secondary Outcomes (8)

• Evaluation of the use of antiparkinsonian drugs will be assessed using the Levodopa Equivalent Daily Dose (LEDD)

  From enrollment to the end of treatment at 52 weeks

• Treatment efficacy will be evaluated using the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS)

  From enrollment to the end of treatment at 52 weeks

• Treatment efficacy will be evaluated using the Patient Global Impression - Improvement scale (PGI-I)

  From enrollment to the end of treatment at 52 weeks

• Treatment efficacy will be evaluated using the Clinical Global Impression - Improvement scale (CGI-I)

  From enrollment to the end of treatment at 52 weeks

• Treatment efficacy will be evaluated using the Mini-Mental State Examination (MMSE)

  From enrollment to the end of treatment at 52 weeks

Study Arms (1)

primary parkinson's disease

EXPERIMENTAL

PDR-001 injection, inject once, 0.4 milliliters each time

Drug: PDR001

Interventions

PDR001 DRUG

This drug was packaged into AAV9 capsids and delivered via bilateral stereotaxic injection into the subthalamic nucleus

primary parkinson's disease

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• Age 40-65 years (inclusive) at screening, either sex;
• Disease duration ≤ 5 years;
• Hoehn \& Yahr stage ≤ 2 in the "off" state.

You may not qualify if:

• Atypical or secondary parkinsonian syndromes (e.g., Parkinson-plus syndromes, hereditary parkinsonism, drug-induced parkinsonism, etc.).
• 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.
• Previous neuroimaging revealing structural brain abnormalities, cerebral vascular malformations, intracranial tumors, risk of intracranial hemorrhage, traumatic brain injury, or other significant findings.
• Mini-Mental State Examination (MMSE) score \< 24.
• Patient Health Questionnaire-9 (PHQ-9) score ≥ 16.
• 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.
• Coagulation disorders or current use of anticoagulants.
• 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.
• Currently receiving antiviral therapy for hepatitis B or C.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

Yi Zhang

CONTACT

64370045; zy12893@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: September 5, 2025
• Study Start: October 20, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: September 5, 2025

Record last verified: 2025-08

Locations

CN (1)