Clinical trial NCT03872713: Establishment of Human Cellular Disease Models for Morquio Disease
Official title: Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Hepatic and Neurological Morquio Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Morquio Disease
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2019-03-13
Enrollment: 40
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient has a diagnosis of Morquio disease

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

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.

Eligibility criteria: Inclusion Criteria:

* Informed consent will be obtained from the patient or the parents before any study related procedures
* Patients of both genders older than 12 months
* Patient has a diagnosis of Morquio disease

Exclusion Criteria:

* No Informed consent from the patient or the parents before any study related procedures
* Patient is younger than 12 months
* Patient has no diagnosis of Morquio disease

Primary outcomes:
measure: Reprogramming patient-derived fibroblasts into induced pluripotent stem cells
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Lahore
country: Pakistan
facility: Childrens Hospital and Institute of Child Health, Ferozepur Road
Study officials:
affiliation: CENTOGENE GmbH Rostock
name: Arndt Rolfs, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: