This is an intervention study to investigate the impact of spinal stimulation on mobility outcomes in children with Cerebral Palsy. Participants will complete a 16-week training program with weekly sessions of spinal stimulation and walking or activity-based training. Participants will also have the option to participate in a randomized control trial to investigate the impact of 5-Azacitidine combined with the spinal stimulation to further affect mobility outcomes.

This project will investigate the impact of transcutaneous spinal cord stimulation (tSCS) on gait and activity-based training in children with Cerebral Palsy. Through a 1:1 randomization, a subset of participants will also receive a dose of 5-azacitidine (AZA), an FDA-approved drug for pediatric oncology, or a placebo. Research in muscle fibers as shown that AZA aids in muscle growth and regeneration. The use of AZA in this study is an off-label application, employed together with the tSCS intervention to investigate the impact of targeting both muscular and mechanical deficits related to CP. This project will also collect blood samples of participants to perform genetic and epigenetic profiling in order to test for correlation with the severity and trajectory of musculoskeletal impairments and with responses to the tSCS and AZA interventions.

The study team hypothesizes that personalized tSCS combined with targeted gait or activity based training will improve motor outcomes in children with spastic CP by reducing muscle tone, improving gait symmetry and neuromotor function, and increasing functional mobility. Furthermore, the addition of a repurposed anabolic agent (AZA) will augment these gains compared to tSCS and training alone.

Children with CP across GMFCS levels will participate in a three-phase protocol, including: (1) a two week baseline phase, (2) a sixteen week intervention phase during which participants will receive tSCS and training interventions, and (3) a four-week post-intervention phase to examine long term outcomes. At the midpoint, participants will receive a single dose of AZA or a single dose of a placebo through a 1:1 randomization. Participants will have a blood draw in phase 1 for genetic and pre-intervention epigenetic profiling and will have a second blood draw in phase 3 for post-intervention epigenetic profiling.

Inclusion Criteria:

• Diagnosis of cerebral palsy (CP) classified as Gross Motor Function Classification System (GMFCS) Levels I-V.
• Between 4 and 17 years old at the time of enrollment/consent.
• Diagnosis of spastic CP hemiplegia, diplegia, or quadriplegia.
• Stable medical condition as determined by the investigator.
• Adequate caregiver support to be able to participate in training and assessment sessions for the duration of the study, at the discretion of the Investigator.
• Capable of performing simple cued motor tasks and can follow 2-3 step commands.
• Capable of communicating an accurate yes or no answer to questions according to parent or guardian.
• Able to localize pain/ discomfort.
• Physician approval for participation.
• Parent/ guardian permission.

Exclusion Criteria:

• Concurrent neurological disease affecting the central nervous system.
• Cardiovascular or musculoskeletal disease or injury that would prevent full participation in physical therapy intervention
• Orthopedic dysfunction, injury, or surgery that would impact an individual's ability to use the upper and/or lower extremity
• Unhealed fracture or other musculoskeletal impairment that might interfere with upper or lower extremity rehabilitation or testing activities
• Implanted stimulator (e.g., epidural stimulator, vagus nerve stimulator, pacemaker, cochlear implant) or drug delivery device (e.g., baclofen pump)
• Dependence on an electro-magnetic medical implant (e.g., cardiac pacemaker, implanted drug pump), ventilation support, or another external device.
• History of uncontrolled seizures
• Unexplained presence of persistent complaints of pain of any kind
• Unable to localize pain/discomfort
• Severe cortico-visual impairment
• Active pressure sores
• Active urinary tract infection
• Active cancer or cancer in remission less than 5 years
• Clinically significant depression, psychiatric disorders, or ongoing drug abuse
• Immunodeficiency or hematologic condition
• Allergy to AZA or mannitol
• Plans to receive a vaccine within 30 days of the planned AZA or placebo injection to take place at week 10
• Pregnancy
• Orthopedic surgery completed in the prior 12 months
• Intrathecal medication titration that may affect muscle spasticity
• Botulinum toxin treatment within 3 months preceding enrollment unless given approval by the treating physician
• Current enrollment in a conflicting research study
• Any other health condition or diagnosis not listed above that may put the participant at risk as determined by the investigator or treating physician

If a participant chooses to opt-in at consent to receive the injection, participants and clinicians will be blinded to their randomization. Caregivers will also be blinded to their child's randomization. Randomization will occur prior to the midpoint assessment.