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

  • End date
    Sep 28, 2022
  • participants needed
  • sponsor
    Joanne Kurtzberg, MD
Updated on 28 January 2021
umbilical cord blood transplantation
ejection fraction
gilbert's disease
brain mri
cortical atrophy
pulmonary function tests
diffusion tensor imaging
metachromatic leukodystrophy
metabolic disorders
niemann pick disease
adjunctive therapy
mutation analysis
metabolic diseases
inborn errors of metabolism
tay sachs disease
demyelinating disease
sandhoff disease
mps iii


The primary objective of the study is to determine the safety and feasibility of intrathecal administration of DUOC-01 as an adjunctive therapy in patients with inborn errors of metabolism who have evidence of early demyelinating disease in the central nervous system (CNS) who are undergoing standard treatment with unrelated umbilical cord blood transplantation (UCBT). The secondary objective of the study is to describe the efficacy of UCBT with intrathecal administration of DUOC-01 in these patients.


The inherited metabolic disorders (IMD) are a heterogeneous group of genetic diseases, most of which involve a single gene mutation resulting in an enzyme defect. In the majority of cases, the enzyme defect leads to the accumulation of substrates that are toxic and/or interfere with normal cellular function. Often times, patients may appear normal at birth but during infancy begin to exhibit disease manifestations, frequently including progressive neurological deterioration due to absent or abnormal brain myelination. The ultimate result is death in later infancy or childhood.

Currently, the only effective therapy to halt the neurologic progression of disease is allogeneic hematopoietic stem cell transplantation (HSCT), which serves as a source of permanent cellular ERT.3 However, one barrier to the success of this therapy is delayed engraftment of donor cells in the CNS when administered through the intravenous route, which is associated with ongoing disease progression over 2-4 months before stabilization. The engraftment of donor cells in a patient with an IMD provides a constant source of enzyme replacement, thereby slowing or halting the progression of disease.

This study will evaluate the safety of a potential new treatment for patients with certain IMDs known to benefit from HSCT using allogeneic UCB donor cells. The new intervention, intrathecal administration of UCB-derived oligodendrocyte-like cells (DUOC-01) will serve as an adjunctive therapy to a standard UCB transplant. The goal of this therapy is to accelerate delivery of donor cells to the CNS thereby bridging the gap between systemic transplant and engraftment of cells in the CNS and preventing disease progression. The DUOC-01 cells and cells used for HSCT will be derived from the same UCB donor unit.

Condition Niemann-Pick Disease, Tay-Sachs Disease, Hunter's Syndrome, Krabbe's Disease, Metachromatic leukodystrophy, Adrenoleukodystrophy, alpha-Mannosidosis, Neuronal ceroid lipofuscinosis, Sandhoff Disease, Pelizaeus-Merzbacher Disease, Brain Diseases, Metabolic, Inborn, Sanfilippo Mucopolysaccharidoses, Neuronal Ceroid Lipofuscinoses (NCL), Hunter Syndrome (MPS II), Metachromatic Leukodystrophy - MLD, Batten Disease, Infantile Neuronal Ceroid Lipofuscinosis, niemann pick disease, tay sachs disease
Treatment DUOC-01
Clinical Study IdentifierNCT02254863
SponsorJoanne Kurtzberg, MD
Last Modified on28 January 2021


Yes No Not Sure

Inclusion Criteria

Patients must be age 1 week to <21 years
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
Adrenoleukodystrophy (ALD) Batten Disease Hunter Syndrome (MPS II) Krabbe
disease (Globoid Leukodystrophy) Metachromatic Leukodystrophy (MLD) Niemann
Pick disease type A or B Pelizaeus-Merzbacher disease (PMD) Sandhoff disease
Tay Sachs disease. Alpha Mannosidosis Sanfilippo (MPS III)
\. 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
% 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 not have a suitable fully matched, non-carrier sibling or related bone marrow donor. 6. Patients must have an available, suitably matched, banked UCB unit in a two-compartment configuration (see graft selection criteria in section 5.2). 7. Patients must have a performance status as follows: Lansky 40%, or Karnofsky 40%. 8. Patients must have a life expectancy of 6 months

Exclusion Criteria

Prior organ, tissue, or stem cell transplant within 3 years of study entry
Prior participation in any gene or regenerative cell therapy study
Inability to have an MRI scan or lumbar puncture
Intractable seizures
Chronic aspiration
Bleeding disorder
Evidence of HIV infection or HIV positive serology
Uncontrolled bacterial, viral, or fungal infection at the time of pre-UCBT cytoreduction
Inability to obtain patient's, parent's or legal guardian's consent
Requirement of ventilatory support
Pregnant or breastfeeding
Active concurrent malignancy, or receiving concurrent radiotherapy, immunosuppressive medications, or cytotoxic chemotherapy
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