Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01331642 |
| Other study ID # |
BG 06-2018 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 20, 2018 |
| Est. completion date |
February 28, 2021 |
Study information
| Verified date |
February 2023 |
| Source |
CENTOGENE GmbH Rostock |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Development of a new mass spectrometry-based biomarker for the early and sensitive diagnosis
of Gaucher Disease from blood (plasma)
Description:
Gaucher disease (GD) is an autosomal recessive hereditary lysosomal storage disorder.
Occurrence of the disease is due to a hereditary deficiency of the Glucocerebrosidase, a
lysosomal enzyme which divides Glucocerebroside into Glucose and Ceramides. The unmetabolised
Glucocerebrosides are stored throughout the whole reticulo-endothelial system. Accumulation
of Glycolipid-enriched macrophages establishes a pathoanatomical phenomenon, the so-called
Gaucher cells, which can be verified by light microscopy of affected tissues. Activation
markers of the macrophages, like the enzyme Chitotriosidase or CCL18, are parameters which
follow the course of GD.
Gaucher disease is the most frequently inherited Sphingolipidosis in the general population,
and in Ashkenazi Jews, in who the prevalence is much higher (1:450). The gene which codes the
Glucocerebrosidase is on the long arm of chromosome 1 and covers 11 exons. So far, more than
200 different mutations in Gaucher patients have been described, mostly missense mutations.
In addition, frame-shift- and splice-site-mutations have been detected, as well as insertions
and deletions. More frequent mutations are N370S, L444P, IVS2+1G>A, c.84insG, R463C and
R496H.
The clinical appearance is heterogeneous. The classical phenotype is characterised by
visceral organ (Hepatosplenomegaly) and skeleton system (Bone marrow infiltrates up to bone
infarcts and pathological fractures) affection. Moreover, consecutive blood cell count
changes, Anemia and Thrombocytopenia are reported.
A serious distinction lies in the appearance of neurological manifestations (myoclonus
epilepsy, hydrocephalus, ocular movement disturbances). There is discussion on whether the
classification into the typical three disease types (type1: non-neuronopathic progress form,
type2: acute neuronopathic progress form, type3: chronic neuronopathic progress form) is
still up-to-date, since it does not sufficiently reflect the reality of the clinical
presentation. A clear genotype-phenotype relationship does not exist. The same DNA mutations
are detected in patients with pronounced differences in disease progression. The exception is
the mutation N370S, which has so far been detected in connection with only visceral progress
forms (type1). At least the outcome of the non-neuronopathic disorder cases could be improved
by the introduction and general availability of enzyme therapy. Under this kind of therapy
there is a reduction of liver and spleen size as well as a normalization of the haemogram
parameters.
New methods, like mass-spectrometry give a good chance to characterize specific metabolic
alterations in the blood (plasma) of affected patients that allow to diagnose in the future
the disease earlier, with a higher sensitivity and specificity. In a pilot study
lyso-glycosylsphingosine has been determined as a sensitive and specific biomarker (see
attached manuscript). This is a metabolic product likely to be involved in the
pathophysiology of the disease. Therefore it is the goal of the study to validate this new
biochemical marker from the blood of the affected patients helping to benefit other patients
by an early diagnose and there-by with an earlier treatment.
