type 2 and 3 spinal muscular atrophy
Conditions
Interventions
Experimental group:GC101 intrathecal injection
Sponsors
Seventh Medical Center of PLA General Hospital
Eligibility
Sex/Gender
All
Age
0.5 Years to 18 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for inclusion in this study. 1.During the screening process, subjects should be aged between 6 months and 18 years (excluding 18 years old), with no gender restrictions. 2.Clinical diagnosis of Type 2 and Type 3 5q SMA; 3.Type 2 patients lack the ability to walk, while Type 3 patients either lack the ability to walk or possess the ability to walk but are unable to squat and stand up independently. 4.Possessing independent sitting ability (defined as: being able to sit independently for more than 5 seconds with the support of one's own upper limbs) 5.One or both hands can only be raised to the height of the mouth; 6.Negative for SMN2 gene modification mutation (c.859 G>C); 7.The subjects or their guardians are able to understand and are willing to comply with the requirements and procedures of the study protocol, voluntarily participate, and sign the informed consent form.
Exclusion criteria
Exclusion criteria: Individuals meeting any of the following criteria will be ineligible to participate in this study. 1. Having participated in any other gene therapy clinical studies; 2. Unable to participate in the late-stage follow-up of the study. 3. Within 30 days prior to the screening period, the use of SMN2-targeted modulating drugs (Spinraza or Risdiplam) has occurred. 4. Serum anti-AAV9 neutralizing antibody titer >1:10 (if serum anti-AAV9 neutralizing antibody titer >1:10, then cerebrospinal fluid anti-AAV9 neutralizing antibody titer will be measured. If cerebrospinal fluid anti-AAV9 neutralizing antibody titer >1:10, the subject will be ineligible for this study). 5. Patients with a predisposition to allergies, including those with hypersensitivity or allergic reactions to prednisolone or other corticosteroids, or their excipients, as well as those with hypersensitivity or allergic reactions to iodine or iodine-containing products. 6. Contraindications to lumbar puncture or intrathecal therapy are present. 7. X-ray examination reveals severe scoliosis of the spine (=50°); 8. Planned or anticipated spinal scoliosis correction surgery within 1 year after administration. 9. Invasive ventilation support or blood oxygen saturation <95%; 10. Severe non-respiratory diseases requiring systemic treatment and/or hospitalization within two weeks prior to the initiation of the study. 11. Occurrence of respiratory infections within four weeks prior to the study that require medical care, medical intervention, or any increase in supportive care. 12. Occurrence of severe non-pulmonary/respiratory infections or concomitant diseases within four weeks prior to the administration of the study drug, which, in the opinion of the principal investigator (PI), may pose unnecessary risks to gene transfer, such as significant renal or liver impairment, known epilepsy, diabetes, idiopathic hypocalciuria, or systemic cardiomyopathy. 13. History of bacterial meningitis or brain or spinal cord diseases, including tumors, or magnetic resonance imaging (MRI) or computed tomography (CT) abnormalities that may interfere with lumbar puncture (LP) or cerebrospinal fluid circulation; 14. Unable to discontinue the use of laxatives or diuretics within 24 hours prior to drug administration; 15. Any serious or active disease other than SMA, which the investigator believes may interfere with the subject's treatment, evaluation, or compliance with the study protocol. Examples include cardiovascular diseases, kidney diseases, liver diseases, endocrine disorders, malignant tumors, diabetes, hypersensitivity, infectious diseases, coagulation abnormalities, immunodeficiency disorders, and severe mental and neurological disorders. 16. Human Immunodeficiency Virus (HIV) antibody-positive, or Hepatitis B surface antigen-positive, or Hepatitis C antibody-positive, or Treponema pallidum (syphilis) antibody-positive; 17. History of alcohol consumption and drug abuse; 18. The investigator deems it inappropriate for the subject to be enrolled in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events (AEs);vital signs;PK blood sampling;immunogenicity sampling;laboratory test indicators; | — |
Secondary
| Measure | Time frame |
|---|---|
| Revised Upper Limb Module (RULM);Hammersmith Functional Motor Scale Expanded (HFMSE) score;electromyography; | — |
Countries
China
Contacts
Public ContactFeng Zhichun
Seventh Medical Center of PLA General Hospital
Outcome results
None listed