Safety and Efficacy Evaluation of GC101 Gene Therapy Via Intrathecal (IT) Injectionin the Treatment of Patients With Type 2 Spinal Muscular Atrophy (SMA) - Phase III

Inclusion Criteria:

• Patients with a confirmed diagnosis of Type 2 5q-SMA through clinical phenotype andgenetic testing.

• Patients who have been receiving regular treatment with nusinersen for more than oneyear prior to screening.

• Patients who have not received treatment with risdiplam within 2 months prior toscreening and have no plans to receive risdiplam treatment within 12 months afterenrollment.

• Patients who can sit independently but cannot walk independently at the time ofscreening (according to the definitions of independent sitting and walking in theWHO-MGRS motor milestones scale), and have an HFMSE score of ≥10 points.

• Patients and/or their legal guardians are able to understand and are willing tocomply with the requirements and procedures of the trial protocol, and voluntarilyparticipate and sign the informed consent form

Exclusion Criteria:

• Patients with serum anti-AAV9 neutralizing antibody titers > 1:50 at the time ofscreening.

• Patients who have received nusinersen treatment within 2 months prior to enrollment.

• Patients with any medical conditions that may affect the interpretation of studyresults or pose a risk to the safety of the participants, including but not limitedto organ dysfunction of any cause, acute infectious diseases, primary/acquiredimmunodeficiency diseases, severe cardiovascular/cerebrovascular diseases,gastrointestinal diseases, diabetes, known epilepsy, meningitis, seizure orconvulsion history, or a family history of psychiatric disorders; and those withcerebrospinal fluid circulation disorders.

• Patients with severe liver injury/hepatic insufficiency of any cause, including butnot limited to alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥3times the upper limit of normal (ULN); total bilirubin (TBil) ≥1.5 times the ULN.

• Patients deemed by the investigator to have contraindications to glucocorticoid use,such as severe hypertension, diabetes, systemic infectious diseases, fungalinfections, glaucoma, osteoporosis, peptic ulcer disease, tuberculosis, etc.

• Patients with contraindications to lumbar puncture or intrathecal injection therapy.

• Patients with any medical conditions that may affect the assessment of motorfunction, such as severe scoliosis, severe joint contracture deformities, plannedspinal correction surgery during the trial period, severe osteoporosis, or a historyof fractures.

• Patients positive for hepatitis B surface antigen (HBsAg), human immunodeficiencyvirus (HIV) antibodies, hepatitis C virus (HCV) antibodies, or syphilis antibodies.

• Patients who have received vaccinations within 2 weeks prior to dosing.

• Patients who have previously received gene therapy or participated in any clinicaltrial within 3 months prior to screening.

• Patients deemed by the investigator to be unsuitable for participation in thisstudy.