Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01536327 |
| Other study ID # |
BMLD 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Withdrawn |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 MS-based biomarker for the early and sensitive diagnosis of
Metachromatic Leu-kodystrophy disease from blood (plasma)
Description:
Metachromatic Leukodystrophy Disease (MLD) is one of a group of genetic disorders called the
leukodystrophies. These diseases impair the growth or development of the myelin sheath, the
fatty covering that acts as an insulator around nerve fibers. Myelin, which lends its colour
to the white matter of the brain, is a complex substance made up of varying lipids (75%) and
proteins (25%). The leukodystrophies are caused by genetic defects in myelin production or
metabolization of the compounds of the myelin sheath. Each of the leukodystrophies is the
result of a defect in the gene that controls one (and only one) of the enzymes responsible
for creating or degrading a part of the myelin. MLD is caused by a deficiency of the enzyme
arylsulfatase A. MLD is one of several lipid storage diseases, which results in the toxic
build-up of fatty materials (lipids) in cells in the nervous system, liver, and kidneys.
There are three forms of MLD: late infantile, juvenile, and adult. Onset of the late
infantile form (the most common MLD) is typically between 12 and 20 months following birth.
Affected children have difficulty walking after the first year of life. Symptoms include
muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of
vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia.
Children may become comatose. Most children with this form of MLD die by age 5. The juvenile
form of MLD (between 3-10 years of age) usually begins with impaired school performance,
mental deterioration, and dementia and then develop symptoms similar to the infantile form
but with slower progression. The adult form commonly begins after age 16 as a psychiatric
dis-order or progressive dementia. Symptoms include impaired concentration, ataxia, seizures,
dementia, and tremor. Due to consanguinity autosomalrecessive disorders such as MLD have
higher prevalence in Arabian countries.
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 pilotstudy
glycosylsphingosin-sulfatid has been determined as a sensitive and specific biomarker. 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 (plasma)
of the affected patients helping to benefit other patients by an early diagnose and thereby
with an earlier treatment. Examining blood samples will allow to determine whether
measurement of the identified marker lyso-Gb1-Sulfatid is feasible in blood samples and will
further promote early detection of MLD.
Though MLD is a pan-ethnic disorder, the prevalence of this autosomal-recessive disorder is
elevated in countries with a higher frequency of consanguinity. Therefore, we estimate that
every 400th newborn in Arabian countries may be eligible for inclusion due to high-grade
suspicion of MLD, while approximately every 2000th newborn in a non-Arabian country may be
eligible.
