Investigating NMJ Defects in SMA Following Central and Peripheral SMN Restoration
This is an observational study to investigate the improvement of NMJ defects in adult patients with SMA following treatment with Risdiplam. Eligible patients will receive treatment with daily oral Risdiplam after receiving approval through their commercial insurance or drug assistance program. All subjects will be evaluated at the baseline visit to determine eligibility. Eligible subjects will be reevaluated after completing six and 12 months of Risdiplam treatment. The study is intending to enroll ten adults with SMA patients with electrodiagnostic evidence of NMJ transmission defect on repetitive nerve stimulation despite previous treatment with Nusinersen.
• Signed Informed Consent Form
• Age 18-65 years at time of signing Informed Consent Form
• Able and willing to provide written informed consent and to comply with the program protocol according to ICH and local regulations
• Ability to comply with the study protocol, in the investigator's judgment
• Adequately recovered from any acute illness at the time of screening, and considered clinically well enough to participate, in the opinion of the treating physician
• Patients with retinopathy of prematurity should have evidence of stable disease
• Genetic confirmation of 5q SMA documented on standard genetic tests for the disorder
• Received nusinersen treatment for ten months or more
• Presence of 10% compound muscle action potential (CMAP) amplitude decrement on 3 Hz repetitive nerve stimulation of the spinal accessory or ulnar nerve
• Negative blood pregnancy test at screening (all women of childbearing potential, including those who have had a tubal ligation), and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation, as below:
• For women who are not prematurely menopausal (≤12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus):agreement to remain abstinent (refrain from heterosexual intercourse) or to use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 28 days after the last dose of study drug.
• The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar,ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception. Barrier methods must always be supplemented with the use of a spermicide.
• Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.