Validating a New Severity Score System for Adults With Type 1 Gaucher Disease (GD1)

2014-07-23 21:08:54 | BioPortfolio


With the participation of an international consortium of investigators, the investigators will evaluate the validity of a new severity score system called DS3 for adult patients with Gaucher disease. The investigators hypothesize that initial DS3 scores will be predictive of both disease progression and patterns of response including imiglucerase dose sensitivity and completeness and maintenance of response and that sequential DS3 scores will accurately portray either clinical progression of disease or improvement in response to treatment. We will also collect DNA specimens that in future research will be used in conjunction with the DS3 scores to evaluate determinants of the clinical course and the response to treatments for Gaucher disease.


GD1 is a prototypical lysosomal storage disorder and the first disorder to have compelling evidence of successful treatment with enzyme replacement therapy. The common clinical manifestations are hematologic cytopenias, hepatomegaly, splenomegaly, and a spectrum of skeletal pathologies. Disease expression is diverse. The rate and extent of disease progression are variable and often independent of the age at which symptoms are first reported1. Despite a long history of treatment efficacy2, there is significant heterogeneity of response among patients with regard to the maximum improvement in hematologic, visceral, bone, and other manifestations and the dynamic speed of response during therapy1-3. There have been few well-designed studies that comprehensively annotate phenotypic variation over time or measure treatment efficacy and dose response. In part, this is attributable to lack of a validated disease severity scoring system for GD1 to standardize the monitoring of progression and treatment response and to define patient cohorts in clinical studies.

DS3 is a method of expressing an integrated assessment of the burden of disease in a given patient. It can be used to monitor patient status, determine endpoints in clinical studies, classify disease phenotypes and compare patients with the same disease. Although frequently referred to as 'disease severity indices,' DS3 instruments may also include measures of disease activity and damage. DS3s utilize a minimal data set to score the patient in a comprehensive manner. They usually are structured as a group of domains (often according to organ system) that are populated with non-redundant items that are valid, reliable, use feasible, standardized methods of assessment, and that are variably weighted based on associated morbidity and mortality. A DS3 for adult GD1 patients was recently developed and subjected to successful preliminary testing for validity, reliability and feasibility4. With respect to changes over time, a minimal clinically important difference was defined. Construct validity has been partially demonstrated. Using 20 patient profiles from the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the instrument was shown to correlate very well with the "gold standard" clinical global impression scale. However, larger scale testing in a population that is representative of the world wide distribution of GD1 phenotypes (including splenectomy patients) is needed and predictive validity has yet to be determined. Moreover, the DS3 has not yet been correlated with disease-specific measures of response such as achievement of therapeutic goals or broadly used biomarkers. Combining retrospective and prospective analysis, this study is designed to address these issues

Study Design

Observational Model: Cohort


Gaucher Disease




Tower Cancer Research Foundation
Beverly Hills
United States


Enrolling by invitation


University Research Foundation for Lysosomal Storage Diseases, Inc.

Results (where available)

View Results


Published on BioPortfolio: 2014-07-23T21:08:54-0400

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Medical and Biotech [MESH] Definitions

An autosomal recessive disorder caused by a deficiency of acid beta-glucosidase (GLUCOSYLCERAMIDASE) leading to intralysosomal accumulation of glycosylceramide mainly in cells of the MONONUCLEAR PHAGOCYTE SYSTEM. The characteristic Gaucher cells, glycosphingolipid-filled HISTIOCYTES, displace normal cells in BONE MARROW and visceral organs causing skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.

A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in GAUCHER DISEASE. EC

Cerebrosides which contain as their polar head group a glucose moiety bound in glycosidic linkage to the hydroxyl group of ceramides. Their accumulation in tissue, due to a defect in beta-glucosidase, is the cause of Gaucher's disease.

Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of the enzyme deficiency (e.g., GLUCOSYLCERAMIDASE replacement for GAUCHER DISEASE).

One of several acid phosphatases in humans, other mammals, plants, and a few prokaryotes. The protein fold of tartrate-resistant acid phosphatase (TRAP) resembles that of the catalytic domain of plant purple acid phosphatase and other serine/threonine-protein phosphatases that also contain a metallophosphoesterase domain. One gene produces the various forms which include purple acid phosphatases from spleen and other tissues. Tartrate-resistant acid phosphatase is a biomarker for pathological states in which it is over-expressed. Such conditions include GAUCHER DISEASE; HODGKIN DISEASE; BONE RESORPTION; and NEOPLASM METASTASIS.

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