A Study on the Safety, Tolerability, and Efficacy of PDR-001 Injection for Bilateral Stereotactic Subthalamic Nucleus (STN) Clearance of α-synuclein
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- PDR-001 treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 <
- •Patient Health Questionnaire-9 (PHQ-9) score ≥
- •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.
研究组 & 干预措施
primary parkinson's disease
PDR-001 injection, inject once, 0.4 milliliters each time
干预措施: PDR001 (Drug)
结局指标
主要结局
PDR-001 treatment-related adverse events as assessed by CTCAE v5.0
时间窗: From enrollment to the end of treatment at 52 weeks
CTCAE 5.0 records the severity of adverse events, which is divided into grades 1 to 5
Titer levels of capsid neutralizing antibodies and binding antibodies against recombinant adeno-associated virus (rAAV) in serum
时间窗: From enrollment to the end of treatment at 52 weeks
Record the titer changes before and after treatment
Titer of rAAV vectors in whole blood
时间窗: From enrollment to the end of treatment at 52 weeks
Record the titer changes before and after treatment
次要结局
- 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)
- Treatment efficacy will be evaluated using the Hamilton Depression Rating Scale (HAM-D, 17-item version)(From enrollment to the end of treatment at 52 weeks)
- Change in anxiety symptoms as measured by the Hamilton Anxiety Rating Scale (HAM-A)(From enrollment to the end of treatment at 52 weeks)
- Change in sleep-related problems as measured by the Parkinson's Disease Sleep Scale-2 (PDSS-2)(From enrollment to the end of treatment at 52 weeks)