Clinical trial NCT03883750: Induced Pluripotent Stem Cells for Niemann Pick Disease
Official title: Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Hepatic and Neurological Niemann Pick Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Niemann-Pick Diseases
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2019-03-21
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The patient has a diagnosis of Niemann Pick disease

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

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.

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 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

Primary outcomes:
measure: To generate patient-specific induced pluripotent stem cells and then differentiate them into neural 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.
role: PRINCIPAL_INVESTIGATOR
References: