Effects of Enzyme Replacement in Gaucher's Disease

NCT00001289 | Completed

• 2 other identifiers: 91022591-N-0225
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Gaucher disease is a lysosomal storage disease resulting from glycocerebroside accumulation in macrophages due to a genetic deficiency of the enzyme glucocerebrosidase. It may occur in adults but occurs most severely in infants, in whom cerebroside also accumulates in neurons. Patients with Gaucher's disease experience enlargement of the liver and spleen and bone destruction. The condition is passed from generation to generation through autosomal recessive inheritance. There are actually three types of Gaucher's disease. Type I is the most common form. It is a chronic non-neuronopathic form, meaning the disease does not affect nerve cells. The symptoms of type I can appear at any age. Type II appears in infancy and usually results in death for the patient. Type II is an acute neuronopathic form and can affect the brain stem. It is the most severe form of the disease. Type III is also neuronopathic, however it is subacute in nature. This means the course of the illness lies somewhere between long-term (chronic) and short-term (acute). The purpose of this study is to examine the effects of enzyme replacement therapy on patients with Gaucher's disease, specifically those types directly affecting the nervous system (neuronopathic). Patients with Gaucher's disease types II and III will be selected to participate in the study and receive enzyme replacement therapy. Patients participating will undergo a variety of tests to measure levels of hemoglobin concentration, liver volume, and spleen volume. Improvements in these measures will be compared other laboratory tests measuring the involvement of the nervous system.

Conditions

Gaucher's Disease

Keywords

Enzyme Replacement; Type 3 Gaucher's Disease; Lysosomal Storage; Supranuclear Gaze Palsy; Seizures; Mental Retardation; Gaucher Disease

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with neuropathic Gaucher's disease who have a partial or complete horizontal supranuclear gaze palsy or a genotype associated with neurological involvement.
• All candidates must be serologically nonreactive for hepatitis B and human immunodeficiency (AIDS) virus. HIV positive patients will be excluded because of the effects of the latter illness on cognitive performance.
• Individuals with neoplastic disease will be excluded.
• The general health and well being of each candidate must be sufficient to allow for a modest amount of blood drawing, collection of appropriate urine and spinal fluid specimens and performance of necessary roentgenographic and magnetic resonance (MR) imaging studies. In addition, each candidate must be able to return to the National Institutes of Health (NIH) on a regular basis dictated by disease severity for monitoring of laboratory parameters.

You may not qualify if:

• Patient who participates in a clinical study of an investigational therapeutic agent for Gaucher Disease.
• Patient and/or the patient's parent(s) or legal guardian(s) are unable to understand the nature, scope, and possible consequences of the study.
• Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, Mankin HJ, Murray GJ, Parker RI, Argoff CE, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. 1991 May 23;324(21):1464-70. doi: 10.1056/NEJM199105233242104.

  PMID: 2023606 BACKGROUND

• Benko W, Ries M, Wiggs EA, Brady RO, Schiffmann R, Fitzgibbon EJ. The saccadic and neurological deficits in type 3 Gaucher disease. PLoS One. 2011;6(7):e22410. doi: 10.1371/journal.pone.0022410. Epub 2011 Jul 20.

  PMID: 21799847 DERIVED

MeSH Terms

Conditions

Gaucher Disease; Seizures; Intellectual Disability

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Mental Disorders

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: September 23, 1991
• Study Completion: March 3, 2008
• Last Updated: July 2, 2017

Record last verified: 2008-03-03

Locations

US (1)