First-in-human STUP-001 gene therapy to convert spinal cord support cells into neurons for chronic spinal cord injury

A Single-center, Prospective Investigator-initiated Trial to Evaluate the Safety and Exploratory Efficacy of STUP-001 in Patients With Chronic Spinal Cord Injury of AIS-A or B Level

This trial will test STUP-001, an AAV gene therapy that aims to convert astrocytes into neurons, in adults 19–60 with chronic AIS-A or AIS-B spinal cord injuries to see if it is safe and shows early signs of helping function.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 19 Years to 60 Years
• Sex: All
• Sponsor: Yonsei University (Academic / other)
• Locations: 1 site (Seoul)
• Trial ID: NCT06922890 on ClinicalTrials.gov

What this trial studies

STUP-001 is an AAV-based in vivo gene therapy designed to directly convert astrocytes into functional neurons within the injured spinal cord. This single-center, prospective, investigator-initiated trial at Severance Hospital will enroll adults aged 19–60 with chronic traumatic spinal cord injury classified as AIS-A or AIS-B and at least 6 months post-injury. Participants will receive STUP-001 and be followed through a 7-month evaluation period focused on safety, tolerability, and exploratory efficacy outcomes. The trial builds on preclinical data showing astrocyte-to-neuron conversion and motor improvement in animal models.

Who should consider this trial

Good fit: Adults 19–60 years old with traumatic chronic spinal cord injury (≥6 months since injury) classified as AIS-A or AIS-B who can consent and meet the study's non-fertility/contraception requirements are the intended participants.

Not a fit: People with non-traumatic or recent injuries (<6 months), less severe AIS grades (C or D), pregnant women, or those outside the specified age range are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, STUP-001 could replace lost neurons, potentially improving motor function and quality of life for people with chronic severe spinal cord injury.

How similar studies have performed: Preclinical studies of STUP-001 showed astrocyte-to-neuron conversion and meaningful motor improvements in animals, but this is the first-in-human application of this direct reprogramming approach.

Eligibility criteria

Inclusion Criteria:

* Male and female adults aged 19 to 60 years at the time of obtaining informed consent.
* Patients diagnosed with traumatic spinal cord injury classified as ASIA Impairment Scale (AIS) grade A or B:

  1. AIS-A: Complete loss of sensory and motor function.
  2. AIS-B: Partial preservation of sensory function with complete motor paralysis
* Patients who have been diagnosed with traumatic spinal cord injury for at least 6 months at the time of screening.

At the time of screening, women must provide evidence of non-fertile status by meeting at least one of the following criteria:

(a) Postmenopausal women: Defined as women over the age of 50 who have been amenorrheic for at least 12 consecutive months after discontinuing all exogenous hormonal treatments.

(b) Women with irreversible surgical infertility, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. (Tubal ligation is not accepted.) (c) Women 50 years or younger who have been amenorrheic for at least 12 consecutive months after discontinuing all exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range defined by the study site.

* Acceptable methods of contraception include:

  1. Complete abstinence.
  2. Tubal sterilization.
  3. Hormonal contraceptives with no known drug interactions (e.g., levonorgestrel intrauterine system (IUS) (Mirena), medroxyprogesterone).
  4. Copper intrauterine device (IUD).
  5. Partner vasectomy. (Note: Periodic abstinence methods (e.g., ovulation timing, symptothermal method, or post-ovulatory methods) and withdrawal are NOT considered acceptable contraception methods.)
* Individuals who are able to understand the provided information and can voluntarily sign the written informed consent (or have a legally authorized representative sign on their behalf).

Exclusion Criteria:

* Patients diagnosed with traumatic spinal cord injury (SCI) classified as AIS-C or D at the time of screening.
* Patients with the following cardiovascular conditions at the time of screening:

  1. Myocardial infarction or unstable angina within the past 6 months.
  2. QTc interval ≥ 450 msec or clinically significant electrocardiographic (ECG) abnormalities.
  3. Congestive heart failure (CHF) classified as New York Heart Association (NYHA) Class II or higher.
  4. Stroke or transient ischemic attack (TIA) within the past 6 months.
* Patients with uncontrolled diabetes mellitus (e.g., HbA1c \> 8% at screening).
* Patients with uncontrolled hypertension (e.g., systolic BP \> 180 mmHg or diastolic BP \> 100 mmHg).
* Patients diagnosed with, undergoing treatment for, or with a history of malignancy within the past 5 years at the time of screening.
* Patients with positive serologic test results for HBsAg, anti-HCV Ab, or anti-HIV Ab at the time of screening. However, patients with positive anti-HCV Ab may be eligible if HCV RNA test results are negative after treatment.
* Patients with clinically significant severe infections, as determined by the investigator (e.g., infections requiring continuous concomitant medication for ≥3 weeks during the clinical trial period).
* Patients with a history of hypersensitivity to any component of the investigational drug.
* Patients with a history of gene or cell therapy involving AAV2.
* Patients with the following abnormal laboratory test results at screening:

  1. WBC \< 2,000/mm³
  2. Platelet count \< 100,000/mm³
  3. Hemoglobin \< 10.0 g/dL
  4. Serum creatinine \> 1.5×ULN
  5. Total bilirubin \> 1.5×ULN
  6. AST, ALT \> 3×ULN
  7. PT-INR/aPTT \> 1.5×ULN
* Patients with substance abuse, alcohol dependence, or psychiatric disorders.
* Patients who are unable to undergo general anesthesia.
* Pregnant or breastfeeding women, or those with a positive pregnancy test at screening.
* Patients who have received another investigational drug within 4 weeks prior to screening. However, patients who have not received an investigational drug or participated in non-interventional observational studies may be eligible.
* Any other individuals deemed ineligible for the clinical trial at the investigator's discretion.

Where this trial is running

Seoul

• Severance Hospital — Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Junsang Yoo, Ph D.

Conditions Spinal Cord Injury; Chronic Spinal Cord Injury; Direct Lineage Reprogramming; Cell Fate Conversion; First-in-Human Multi-Cistronic Vector Application