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Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation

Phase 2
21 Years
Not Enrolling
Hurler's Syndrome, Maroteaux-Lamy Syndrome, Sly Syndrome, Alpha Mannosidosis, Fucosidosis, Aspartylglucosaminuria, Sphingolipidoses, Krabbe Disease, Wolman's Disease, Niemann-Pick Disease Type B, Niemann-Pick Disease, Type C

Thank you

Trial Information

Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation

This has been an ongoing area of interest by our group at the Univ. of Minnesota, but this
is a new protocol to take the place of several older protocols. While survival has been
very good on the prior protocols over the past decade, incomplete engraftment has remained
somewhat problematic. Therefore, we have modified the preparative regimen somewhat to
increase engraftment by replacing anti-thymocyte globulin (ATG) with Campath-1H, a drug that
is more immune suppressive. In addition, we have modified the supportive care regimen.
Based on this, we will monitor levels of an anti-oxidant therapy (N-acetylcysteine) and
biomarkers of inflammation and oxidative stress for the families that consent to these
research studies.

Inclusion Criteria:

- Mucopolysaccharidosis (MPS) Disorders:

- MPS IH (Hurler syndrome)

- MPS-VI (Maroteaux-Lamy syndrome)

- MPS VII (Sly syndrome).

- Glycoprotein metabolic disorders:

- Alpha mannosidosis

- Fucosidosis

- Aspartylglucosaminuria

- Sphingolipidoses and Recessive Leukodystrophies: Presymptomatic patients with
globoid cell leukodystrophy (GLD, also known as Krabbe disease) and metachromatic
leukodystrophy (MLD) will be eligible for treatment on this protocol. White matter
disease by magnetic resonance imaging (MRI) alone is not an exclusion if the patient
is asymptomatic.

- Peroxisomal Disorders: Presymptomatic patients with inherited peroxisomal disorders
associated with of very long chain fatty acids (VLCFA) elevation, identified by
family history or laboratory testing (including neonatal screening), are eligible for
this protocol. White matter disease by MRI alone is not an exclusion if the patient
is asymptomatic.

- Other Inherited Diseases of Metabolism:

- Wolman syndrome (acid lipase deficiency)

- Niemann-Pick B patients (sphingomyelin deficiency)

- Niemann-Pick C subtype 2

- Donor Availability: Patients considered for transplantation must have a sufficient
graft as based on current criteria of the University of Minnesota Blood and Marrow
Transplantation Program: Priority will be as follows, although in circumstances in
which timing is of the essence, cord blood grafts may be chosen over an unrelated
graft, despite the priority listed above.

- Multidisciplinary Evaluation: Patients will be eligible for transplantation only
after they are seen and evaluated by members of the Inherited Metabolic and Storage
Disease Program (IMSD) team, and the team has offered transplantation to the

Exclusion Criteria:

- Symptomatic patients with peroxisomal or lysosomal disorders are excluded but may be
considered for other treatment protocols.

- Major organ dysfunction. Evidence of major organ impairment, including:

- Cardiac: left ventricular ejection fraction <40%

- Renal: serum creatinine >2.5 x normal for age

- Hepatic: total bilirubin >3 x normal, or Alanine transaminase (ALT) > 3 x

- Pulmonary: requirement for continuous oxygen supplementation

- Pregnancy

- Evidence of human immunodeficiency virus (HIV) infection or known HIV positive

- Patients >21 years of age.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients Achieving Engraftment

Outcome Description:

Rate of successful engraftment - patients who achieved and sustained donor engraftment; donor chimerism by day 100 of at least 90% after undergoing hematopoietic stem cell transplantation.

Outcome Time Frame:

Day 100

Safety Issue:


Principal Investigator

Paul Orchard, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Minnesota Medical Center


United States: Institutional Review Board

Study ID:




Start Date:

March 2008

Completion Date:

February 2010

Related Keywords:

  • Hurler's Syndrome
  • Maroteaux-Lamy Syndrome
  • Sly Syndrome
  • Alpha Mannosidosis
  • Fucosidosis
  • Aspartylglucosaminuria
  • Sphingolipidoses
  • Krabbe Disease
  • Wolman's Disease
  • Niemann-Pick Disease Type B
  • Niemann-Pick Disease, Type C
  • Inborn errors of metabolism
  • Sphingolipidoses
  • Recessive Leukodystrophies- GLD, Krabbe disease, MLD
  • Peroxisomal Disorders
  • Wolman syndrome
  • Niemann-Pick B patients
  • Niemann-Pick C subtype 2
  • Fucosidosis
  • Leukodystrophy, Globoid Cell
  • Alpha-Mannosidosis
  • Mannosidase Deficiency Diseases
  • Metabolism, Inborn Errors
  • Mucopolysaccharidosis VI
  • Niemann-Pick Diseases
  • Niemann-Pick Disease, Type A
  • Niemann-Pick Disease, Type C
  • Sphingolipidoses
  • Wolman Disease
  • Cholesterol Ester Storage Disease
  • Mucopolysaccharidosis VII
  • Mucopolysaccharidosis I
  • Aphasia, Primary Progressive
  • Pick Disease of the Brain
  • Frontotemporal Dementia
  • Aspartylglucosaminuria
  • Niemann-Pick Disease, Type B



University of Minnesota, Fairview Minneapolis, Minnesota  55455