Establishment of Genetic Basis for Neurological Disease by Genetic Screening

Establishment of Genetic Basis for Neurological Disease by Genetic Screening and Development of Disease-specific Induced Pluripotent Stem (iPS) Cells From Dermal Fibroblasts in Selected Patients

Hereditary neurological disorders are relatively common in paediatric neurological practice, but it has considerable overlap with adult neurological disorders. It is a group of of genetic diseases, most of which with a Mendelian inheritance affecting neurological system. Pathogenic mechanisms of these diseases are not fully understood. There is currently no effective therapy for most of these diseases. Disease-specific and patient- specific iPS cells would provide useful source of cells in culture modeling in these diseases.

In this study, disease-specific iPS cell lines repositories from hereditary neurological disease patients will be established. The cell lines will be registered and make them available to other investigators.

Study Overview

• Status: Enrolling by invitation
• Conditions: Neuro-Degenerative Disease
• Intervention / Treatment: Genetic: Genechip screening kit

Detailed Description

The human iPS is generated by direct reprogramming of human somatic cells. These hiPS cells can give rise to most tissue types in the human embryo and possess many of the properties of human embryonic stem cells (hESC). The big advantage of human iPS cell over hESC is that it circumvents most of the limitations of hESC and remains the pluripotency for regeneration of cells and tissues. The unique capacity of self-renewal of iPS can provide unlimited supply of pluripotent stem cells for study. The patient-specific iPS cell lines should fundamentally eliminate the concern of immune rejection and ethical issues. The disease-specific iPS will facilitate the study of the mechanism of nucleotide expansion. It is the ideal medium to study the dynamic changes of the expansion from stem cell stage to different differentiation stages. It also creates a platform for drug development. The establishment of iPS stem cells will also make it realistic for target gene replacement/correction therapy.

Study subjects will be identified at the members from the Hong Kong Spinocerebellar ataxias (SCA) association and neurology clinic in Prince of Wales Hospital. Patients identify based on the diagnosis, genetic test results and inclusion and exclusion criteria.

10ml blood sample for genetic screening will be collected. Skin biopsy will only be scheduled if pathogenic mutation was identified by the genetic screening test and generation of iPS is considered necessary to study the pathogenic mechanism of the disease.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin
    • Hong Kong, Shatin, Hong Kong, 000
      • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Subjects who have presumed hereditary neurological disease

Description

Inclusion Criteria:

1. Individuals at age 18 years or older who have presumed hereditary neurological disease.
2. Individuals or his/her guardian who can provide the informed consent.

Exclusion Criteria:

1. Individuals who are allergic to local anesthetics.
2. Individuals who have serious medical conditions that restrict their ability to tolerate skin biopsy.
3. Individuals who have history of bleeding diathesis or use of anticoagulant medications. Patients taking nonsteroidal anti-inflammatory agents will be asked to discontinue these medications 3 days prior to skin biopsy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific genetic mutation	Able to identify disease-specific genetic mutation	1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Anne CHAN, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2012
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 23, 2017
• First Submitted That Met QC Criteria: October 23, 2017
• First Posted (Actual): October 26, 2017

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 25, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: genetic screening; neuro-degenerative disease
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurodegenerative Diseases
• Other Study ID Numbers: iPS gene study CRE-2012.361

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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