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Establishment of Human Cellular Disease Models for Morquio Disease (IPSMORQUIO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03872713
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : April 25, 2019
Information provided by (Responsible Party):
Centogene AG Rostock

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

Condition or disease
Morquio 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.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Hepatic and Neurological Morquio Disease
Actual Study Start Date : October 26, 2018
Estimated Primary Completion Date : October 26, 2020
Estimated Study Completion Date : October 26, 2020

Primary Outcome Measures :
  1. Reprogramming patient-derived fibroblasts into induced pluripotent stem cells [ Time Frame: 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

Biospecimen Retention:   Samples With DNA
The skin biopsy will be carried out for patients with a diagnosis of Niemann Pick. The biopsy is performed by the physician by means of punch biopsy (diameter 2-3 mm) under local anesthesia, preferably on the forearm (alternatively: thigh). The biopsy is immediately transferred to sterile cell culture medium and sent by center representative for the quickest possible processing to CENTOGENE's laboratory located in Germany or to professional collaborators being part of the project.

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patient has a diagnosis of Morquio disease

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03872713

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Contact: Volha Skrahina, Dr +4938180113594 ext 594

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Childrens Hospital and Institute of Child Health, Ferozepur Road Recruiting
Lahore, Pakistan, 54600
Contact: Huma Arshad Cheema, Prof.         
Contact: Nadeem Anjum, MD         
Sub-Investigator: Nadeem Anjum, MD         
Principal Investigator: Huma Arshad Cheema, Prof.         
Sponsors and Collaborators
Centogene AG Rostock
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Study Director: Arndt Rolfs, Prof. MD. Centogene AG Rostock

Additional Information:
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Responsible Party: Centogene AG Rostock Identifier: NCT03872713    
Other Study ID Numbers: IPSM 09-2018
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mucopolysaccharidosis IV
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases