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Development of iPS From Donated Somatic Cells of Patients With Neurological Diseases

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ClinicalTrials.gov Identifier: NCT00874783
Recruitment Status : Recruiting
First Posted : April 3, 2009
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Hadassah Medical Organization

Tracking Information
First Submitted Date April 2, 2009
First Posted Date April 3, 2009
Last Update Posted Date August 20, 2019
Actual Study Start Date April 2009
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures Not Provided
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00874783 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Development of iPS From Donated Somatic Cells of Patients With Neurological Diseases
Official Title Derivation of Induced Pluripotent Stem Cells From Somatic Cells Donated by Patients With Neurological Diseases for the Study of the Pathogenesis of the Disorders and Development of Novel Therapies
Brief Summary

Human fibroblasts and possibly other human somatic cells may be reprogrammed into induced pluripotent stem (iPS) cells by the forced expression of transcription factors (1-5). The iPS cells seem to share many properties with human embryonic stem cells.

Induced pluripotent stem cells potentially may be useful in the future as an unlimited source of cells for transplantation.

The major goal of the project is to develop human iPS cells from cell cultures from skin biopsies or the patient's hair. The iPS cells will be developed primarily for modeling diseases and drug discovery as well as basic research, and for developing the technology that may eventually allow the use of iPS cells for future transplantation therapy. The iPS cells developed in the course of this application are not intended for use in transplantation therapy. Future development of iPS cells for clinical transplantation therapies will be subjected to the appropriate authorization by ethical and regulatory committees.

Detailed Description

The derivation of human iPS cells (1-5) open new avenues to model human diseases since it may now be possible to develop iPS cells from the fibroblasts or other somatic cells of patients with various conditions. These iPS cells may be directed to differentiate into the cells which are affected in specific conditions. Abnormalities in the development of the affected cells as well as altered survival or function of the cells may be studied. Thus iPS cells may serve as an invaluable model for the study of the pathogenesis of human diseases and may also serve for the development of new drugs, and high throughput screening of molecules for toxic or therapeutic effects.

In addition to the great potential of iPS cells for disease modelling and transplantation therapy, the cells may have broad applications in basic research in various areas such as reprogramming, basic development and others.

At present, it is still unclear whether the properties of iPS cells are identical to those of hESCs. Initial data suggest that human iPS cells are indeed similar to hESCs in their phenotype, epigenetic status of pluripotent self-specific genes, telomerase activity, gene expression profile and in their capability to differentiate into progeny of the three germ layers both in vitro and in vivo in teratomas (2, 3, 5). In the mouse system, directed differentiation of iPS cells into bone marrow repopulating hematopoietic stem cells and functional dopaminergic neurons was demonstrated (6, 7). However, incomplete silencing of the constitutive expression of the transcription factors that were used to induce reprogramming can probably interfere with differentiation (1). Further studies are required to confirm that the developmental potential and biological properties of iPS cells are identical to hESC.

Currently, retroviral vectors are most commonly used to introduce and express the transgenes which reprogram the somatic nucleus (1-5). The use of retroviral vectors, which integrate into the host cell genome, may cause hazardous insertion mutagenesis. Moreover, the use of potentially oncogenic transcription factors, such as c-Myc, significantly limits the clinical use of human iPS cells for future cell therapy. However, successful derivation of iPS cells was demonstrated without the forced expression of c-Myc. The decreased efficiency of reprogramming, in the absence of overexpressed c-Myc, may be improved by molecules which act via epigenetic mechanisms. Moreover, successful derivation of iPS cells was recently reported with the use of non-integrating adeno viral vectors or repeated transfections. Thus it appears that with further developments, it may be possible in the future to safely induce pluripotent cells from somatic cells for therapeutic applications.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
donation of a skin specimen of up to 10mm in diameter from skin which will be removed in a surgical operation from a patient who is scheduled to undergo an operation for medical reasons and with no relation to the study at hand.
Sampling Method Non-Probability Sample
Study Population 120 donors to cover 10 different neurodegenerative disorders (previously specified) based on 10 donors per disorder and 20 healthy control donors.
Condition Neurodegenerative Disorders
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007 Dec 21;318(5858):1917-20. Epub 2007 Nov 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April¬†2,¬†2009)
120
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2025
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Donors suffering from different (specified) neurodegenerative disorders scheduled to undergo surgery for medical reasons or will donate a single or a few hairs--to be removed intact from the scull or other areas in the body.
  • Healthy donors scheduled to undergo surgery for medical reasons or will donate a single or a few hairs--to be removed intact from the scull or other areas in the body.

Exclusion Criteria:

  • None
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Benjamin E. Reubinoff, MD PhD 011-972-2-677-4569 benjaminr@ekmd.huji.ac.il
Listed Location Countries Israel
Removed Location Countries  
 
Administrative Information
NCT Number NCT00874783
Other Study ID Numbers 0599-08-HMO-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Hadassah Medical Organization
Study Sponsor Hadassah Medical Organization
Collaborators Not Provided
Investigators
Principal Investigator: Benjamin E Reubinoff, MD, PhD Hadassah Medical Organization
PRS Account Hadassah Medical Organization
Verification Date August 2019