Induced Pluripotent Stem Cells for Niemann Pick Disease (IPSNPABC)

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

Establishment of individualized human cellular disease models based on induced pluripotent stem cells that reflect the broad heterogeneous phenotypic spectrum of Niemann Pick disease

Study Overview

• Status: Completed
• Conditions: Niemann-Pick Diseases

Detailed Description

Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants, children, or adults. Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs. Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. The classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy, and dementia. Dystonia and seizures are common. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible; death usually occurs in the late second or third decade from aspiration pneumonia. Adults are more likely to present with dementia or psychiatric symptoms. The diagnosis of NPC is confirmed by biochemical testing that demonstrates impaired cholesterol esterification and positive filipin staining in cultured fibroblasts. Biochemical testing for carrier status is unreliable. Most individuals with NPC have NPC1, caused by mutations in the NPC1 gene; fewer than 20 individuals have been diagnosed with NPC2, caused by mutations in the NPC2 gene. Molecular genetic testing of the NPC1 genes detects disease-causing mutations in approximately 94% of individuals with NPC. Such testing is available clinically.

NPC is inherited in an autosomal recessive manner. The phenotype (i.e., age of onset and severity of symptoms) usually runs true in families. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible when the two disease-causing mutations have been identified in the family.

Though NPC is a pan-ethnic disorder, the prevalence of this autosomal-recessive disorder is elevated in countries with a higher frequency of consanguinity.

Therefore, the goal of the study to prepare a cell culture from patients affected with Niemann Pick 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: 6 months to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The patient has a diagnosis of Niemann Pick 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 6 months and younger than 80 years
• The patient has a diagnosis of Niemann Pick disease

Exclusion Criteria:

• No Informed consent from the patient or the parents before any study related procedures
• Patients of both genders younger than 6 months or older than 80 years
• No diagnosis of Niemann Pick disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To generate patient-specific induced pluripotent stem cells and then differentiate them into neural cells	The aim of this study is to generate patient-specific induced pluripotent stem cells and then differentiate them into neural cells to study the misfolded proteins in endoplasmic reticulum, their role in untranslated protein response, and possible mechanisms to shuttle the misfolded proteins into lysosomes.	24 months

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2018
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (Actual): March 21, 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: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Genetic Diseases, Inborn; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Dementia; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Language Disorders; Communication Disorders; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
• Other Study ID Numbers: IPSNPABC 6-2018

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