Testing if PDR-001 Can Safely and Effectively Remove Harmful Brain Protein in Parkinson's Disease
Recruiting · NCT07157345 · Interventional (participants receive a specific treatment) · Lead sponsor: Ruijin Hospital
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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.
Who can take part
Inclusion criteria
- To be eligible for inclusion in this clinical study, all of the following criteria must be met:
- 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.
Exclusion criteria
- Exclusion Criteria
- 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.
Where it is running
1 location listed.
- Ruijin hospital - Shanghai, Shanghai Municipality, China