Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

Inclusion Criteria

• •1. Patients must have a confirmed diagnosis of inherited metabolic disorder / inborn error of metabolism. Diagnosis should be confirmed by appropriate test(s) (enzyme and/or mutation analysis) before study entry. Patients must not be eligible for myeloablative chemotherapy as a preparative regimen for transplant due to age, co-morbidities or organ dysfunction.
• •Inborn errors of metabolism / Inherited Metabolic Disorders (IMD) eligible for this study include the following:
• •* Hurler Syndrome (MPS I)
• •* Hurler-Scheie Syndrome with early neurologic involvement and/or sensitization to ERT
• •* Hunter Syndrome (MPS II)
• •* Sanfilippo Syndrome (MPS III)
• •* Krabbe Disease (Globoid Leukodystrophy)
• •* Metachromatic Leukodystrophy (MLD)
• •* Adrenoleukodystrophy (ALD and AMN)
• •* Sandhoff Disease
• •* Tay Sachs Disease
• •* Pelizaeus Merzbacher (PMD)
• •* Niemann-Pick Disease
• •* Alpha-mannosidosis
• •2. Patients must have adequate function of other organ systems as measured by:
• •* Creatinine less than or equal to 2.0 mg/dl and creatinine clearance ≥60 cc/min/1.73m2. Newborns must have a creatinine clearance ≥ 25 cc/min. For babies less than or equal to 3 months of age, the raw value on glomerular filtration rate (GFR) must be ≥ 1 cc/kg/min.
• •* Hepatic transaminases (ALT/AST) 2.5 x normal, bilirubin \<2.0mg/dl
• •* Normal cardiac function by echocardiogram or radionuclide scan (ejection fraction or shortening fraction \>80% of normal value for age)
• •* Pulmonary function tests (PFTs) demonstrating forced expiratory volume at one second (FEV1) of ≥50% of predicted for age. If child is too young or unable to perform PFTs, crying vital capacity result of \>50% of normal value for age or resting pulse oximeter \>92% on room air or clearance by pulmonologist will be required.
• •3. Patient must have a related donor (identical or mismatched for 1, 2 or 3 Human Leukocyte Antigen (HLA)-A, -B or -DR loci).
• •4. Patient, and parent, or legal guardian must have given written informed consent according to FDA guidelines.
• •5. Patients must have a minimum life expectancy of at least 6 months.
• •6. Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy).
• •7. There is no upper or lower age limit for this study.