UCB Transplant of Inherited Metabolic Diseases with Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

Eligibility Criteria

• 1. Patients must be age ≥1 week to ≤21 years.
• 2. Patients must have one of the following inherited metabolic diseases detected by enzyme or mutation analysis, and confirmed by repeat testing on a separately obtained sample:
• 3. Patients must have neurologic evidence of their disease, either clinically or via neuroimaging or neurophysiological testing. Examples of evidence of neurologic involvement include, but are not limited to the following:
• * Abnormal EEG, Brainstem Auditory Evoked Response (BAER), and/or Visual Evoked Potentials (VEP).
• * Abnormal brain MRI, ie. increased Loes score (measure of white matter damage, demyelination, and brain atrophy) and/or abnormal corticospinal tracts as assessed by MRI with diffusion tensor imaging (DTI).
• * Three or more of the early clinical markers: problems sleeping, increased activity, behavior difficulties, seizure-like activity, chewing behavior, inappropriate bladder training, inappropriate bowel training.
• 4. Patients must have adequate organ function as measured by:
• * Renal: Serum creatinine ≤ 2.0 mg/dl
• * Hepatic: Hepatic transaminases (ALT/AST) ≤ 5 x normal, bilirubin ≤ 2.0 mg/dl (except in patients with Gilbert's disease or newborns with physiological or breast milk associated jaundice).
• * Cardiac: Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction
• * 80% of normal value for age). Patients with acquired or congenital cardiomyopathy may receive melphalan as a substitute for cyclophosphamide.
• * Pulmonary: Pulmonary function tests demonstrating FVC, FEV1, and DLCO ≥ 60% of predicted in patients who can complete the testing. If patient cannot perform PFT's, an O2 sat must be \>90% on room air.
• 5. Patients must have an available, suitably matched, banked UCB unit for transplant.
• 6. Patients must have a performance status as follows: Lansky ≥ 40%, or Karnofsky ≥ 40%
• 7. Patients must have a life expectancy of ≥ 6 months.
• 1. Prior organ, tissue, or stem cell transplant within 3 years of study entry.
• 2. Prior participation in any gene or regenerative cell therapy study.
• 3. Inability to have an MRI scan or lumbar puncture.
• 4. Intractable seizures.
• 5. Chronic aspiration.
• 6. Bleeding disorder.
• 7. Evidence of HIV infection or HIV positive serology.
• 8. Uncontrolled bacterial, viral, or fungal infection at the time of pre-UCBT cytoreduction.
• 9. Inability to obtain patient's, parent's or legal guardian's consent.
• 10. Requirement of ventilatory support.
• 11. Pregnant or breastfeeding.
• 12. Active concurrent malignancy, or receiving concurrent radiotherapy, immunosuppressive medications, or cytotoxic chemotherapy