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

Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Hepatic and Neurological Morquio Disease

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

Study Overview

• Status: Completed
• Conditions: 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.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Pakistan
  • Lahore, Pakistan, 54600
    • Childrens Hospital and Institute of Child Health, Ferozepur Road

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patient has a diagnosis of Morquio disease

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reprogramming patient-derived fibroblasts into induced pluripotent stem cells	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	24 months

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock

Publications and helpful links

Helpful Links

• Centogene is one of the leading companies focusing on genetic testing for rare hereditary disorders.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 26, 2018
• Primary Completion (ACTUAL): December 1, 2019
• Study Completion (ACTUAL): December 1, 2019

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (ACTUAL): March 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Bone Diseases, Developmental; Mucopolysaccharidoses; Osteochondrodysplasias; Mucopolysaccharidosis IV
• Other Study ID Numbers: IPSM 09-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No