NCT03612310

Developing Protocols for Modelling of Genetic Diseases Using Induced Pluripotent Stem Cells

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 3,000 (estimated)
• Sponsor: Kevin Bruce · Industry
• Sex: All
• Age: 1 Year – 120 Years
• Healthy volunteers: —

Summary

Recent advances have shown that cells from human blood, skin and urine samples can be reprogrammed to become stem cells. These are called induced Pluripotent Stem Cells (iPSCs) and share many characteristics with embryonic stem cells, including an unlimited capacity for proliferation and the potential to become any cell in the body. Beneficially, the use of iPSCs avoids the ethical difficulties which surround embryonic stem cells and allows generation of iPSC lines which are disease representative. For example, we could take skin samples from an individual diagnosed with Huntington's disease and their unaffected sibling and using this technology, generate iPSC lines from both individuals. Using these iPSCs, we could produce disease affected cell populations from the affected and unaffected individuals, use these cells to research why specific cell populations are affected by disease and test new treatments to combat disease progression, essentially producing a 'disease in a dish'. This is just one example of many for which this technology could be applied. We can also utilise gene-editing techniques to generate isogenic controls or insert disease related mutations to assess disease phenotype. Although generation of iPSC lines has been robustly proven across multiple disease backgrounds, many aspects of their downstream use still remain to be determined. Particularly, robust protocols for directing iPSCs towards cell fates such as neurons or blood cells must be developed to fully realise application of iPSCs in disease modelling and drug screening. This study involves the collection of human blood, skin or urine samples from subjects bearing a range of genetic diseases alongside those from individuals who have not been diagnosed with a disease, as controls. These samples will be used to generate iPSC lines for development of differentiation and disease phenotyping protocols.

Detailed description

Recent advances in biotechnology have shown that somatic cells (such as skin, blood and urine cells) from human adults and children can be reprogrammed to change their characteristics and become other types of cells that may be useful for disease modelling and drug screening. This includes the generation of induced pluripotent stem cells (iPS cells) which can be derived from these somatic cells by a process known as "cellular reprogramming". These iPSCs share many characteristics with embryonic stem cells, including an unlimited capacity for proliferation and the potential to differentiate into any cell of the body. However, unlike embryonic stem cells, the generation of iPSCs avoids the practical and ethical difficulties of obtaining embryonic tissues. Consequently, cellular reprogramming and iPSC technology has great implications in the field of disease modelling and drug screening. Many obstacles must be overcome before iPSC based disease modelling and drug screening can fully be realised and allow replacement of inadequate animal models and simplistic cell models. This study will enable us to gather samples from a range of participants from different disease backgrounds, and to develop suitable panels of iPSCs for the purpose of protocol development. Development of robust protocols which are suitable for use across multiple iPSC lines and repeatable across multiple laboratories are essential for the use of iPSCs in disease modelling and drug screening. This study will allow us to look at causation of disease across a range of disease specific cell lines with known genetic backgrounds which are representative of a cohort of human patients. This is fundamental for development of iPSC based drug screening assays.

Conditions

• Genetic Disease

Interventions

Type	Name	Description
PROCEDURE	Skin biopsy/Urine Collection/Blood Sample Collection	Participant will meet clinician in a suitable local clinical setting, in select circumstances the clinician may attend the participants home. Clinician will collect a 5-7mm section of skin, the area may be numbed beforehand and stitches may be used to close the wound when required. The wound will be dressed if deemed necessary by medical professional. Participant will meet clinician in a suitable local clinical setting, in select circumstances the clinician may attend the participants home. The clinician or phlebotomost will use a disposable needle to remove a blood sample (normally 50ml but could be up to 320ml for adults). Participant will meet clinician in a suitable local clinical setting, in select circumstances the clinician may attend the participants home. The clinician or other nominated member of the clinical team will provide a sterile urine collection vessel and direct the volunteer to a suitable private toilet area to provide the sample.

Timeline

• Start date: 2018-11-01
• Primary completion: 2020-07-01
• Completion: 2028-07-01
• First posted: 2018-08-02
• Last updated: 2018-08-02