IPSMORQUIO: Establishment of Human Cellular Disease Models for Morquio Disease
Study Details
Study Description
Brief Summary
Establishment of human cellular disease models for Morquio disease for an individualized therapy development having the capacity to address both hepatic and neurologic forms of the disease
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Detailed Description
The mucopolysaccharidoses are a group of inherited lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain carbohydrates and fats. In individuals with MPS disorders, deficiency or malfunction of specific lysosomal enzymes lead to an abnormal accumulation of certain complex carbohydrates (mucopolysaccharides or glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin and/or teeth. These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow. This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body. There are several different types and subtypes of mucopolysaccharidosis. These disorders, with one exception, are inherited as autosomal recessive traits and all vary in their clinical phenotype. Within our clinical trial we focus on MPS type IV.
Morquio syndrome (mucopolysaccharidosis type IV; MPS IV) is a mucopolysaccharide storage disease that exists in two forms (Morquio syndromes A and B) and occurs because of a deficiency of the enzymes N-acetyl-galactosamine-6-sulfatase and beta-galactosidase, respectively. A deficiency of either enzyme leads to the accumulation of mucopolysaccharides in the body, abnormal skeletal development, and additional symptoms. In most cases, individuals with Morquio syndrome have normal intelligence. The clinical features of MPS IV-B are less severe than those associated with MPS IV-A. Symptoms may include growth retardation, a prominent lower face, an abnormally short neck, knees that are abnormally close together (knock knees or genu valgum), flat feet, abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis), abnormal development of the growing ends of the long bones (epiphyses) resulting in dwarfism, and/or a prominent breast bone (pectus carinatum) as well as bell shaped chest. Though the CNS and peripheral nerves are primarily not affected the bone defects may result in neurological symptoms such as spinal cord compression. Hearing loss, weakness of the legs, and/or additional abnormalities may also occur.
The goal of the study is to prepare a cell culture from patients affected with Morquio disease in order to identify novel pathways and proteins involved in disease progression that allow for an earlier diagnosis (i.e. before symptom onset) and that are suitable targets for an individualized therapeutic approach able to address not only the hepatic form, but also the neurologic form of the disease, which is less responsive to the current therapeutic approaches.
Study Design
Outcome Measures
Primary Outcome Measures
- Reprogramming patient-derived fibroblasts into induced pluripotent stem cells [24 months]
The aim of this study is to generate patient-specific induced pluripotent stem cells and then differentiate them into chondrocytes to study the accumulation of keratin sulfate (KS) and chondroitin-6-sulfate (C6S), and possible mechanism to reduce the accumulated substances and modulate the defective enzyme
Eligibility Criteria
Criteria
Inclusion Criteria:
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Informed consent will be obtained from the patient or the parents before any study related procedures
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Patients of both genders older than 12 months
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Patient has a diagnosis of Morquio disease
Exclusion Criteria:
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No Informed consent from the patient or the parents before any study related procedures
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Patient is younger than 12 months
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Patient has no diagnosis of Morquio disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Childrens Hospital and Institute of Child Health, Ferozepur Road | Lahore | Pakistan | 54600 |
Sponsors and Collaborators
- CENTOGENE GmbH Rostock
Investigators
- Principal Investigator: Arndt Rolfs, Prof. Dr., CENTOGENE GmbH Rostock
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Centogene is one of the leading companies focusing on genetic testing for rare hereditary disorders.
Publications
None provided.- IPSM 09-2018