Stem Cell Models of Best Disease and Other Retinal Degenerative Diseases.


Background: Autosomal recessive bestrophinopathy (ARB) is one of 5 blinding eye diseases caused by mutations in the gene BEST1. These diseases, collectively termed "bestrophinopathies" include ARB, Best vitelliform macular dystrophy (BVMD), adult-onset vitelliform dystrophy (AVMD), autosomal dominant vitreoretinalchoroidopathy (ADVIRC) and retinitis pigmentosa (RP) . Objective: To collect DNA/RNA and skin samples from individuals with ARB or other diseases due to mutations in the gene BEST1. These models will be used to identify and test therapeutic approaches to treating these diseases. Design: Study involves a one time donation of a skin punch biopsy and whole blood. Once the skin biopsy is obtained, skin fibroblasts will be isolated, which will be reprogrammed into iPSCs. RPE cells will be derived from the iPSCs

Full Title of Study: “Development of Induced Pluripotent Stem Cells From Patients With Best Disease and Other Inherited Retinal Degenerative Diseases.”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: December 2021

Detailed Description

The PI on this proposal has been studying BEST1 and the protein encoded (Best1) since its discovery in 1998. Best1 is an integral membrane protein that in the eye is expressed only by retinal pigment epithelial (RPE) cells where it is localized to the basolateral plasma membrane. Methods: Once a subject has been identified as a potential candidate, a study coordinator will meet with the subject, to discuss the study prior to sample collection. The study coordinator will review the consent form with the subject and spend as much time as necessary answering any questions. Once the subject has signed the consent form, study procedures will begin. Following the consent process, a skin sample will be obtained from subjects using a (4mm) dermal punch biopsy method. This will be accomplished in a single visit to the Regenerative Medicine Consult Service or other approved clinical examination room. A suture may need to be placed following this skin biopsy. A health care provider (either at Mayo Clinic or a local health care provider's office) can remove the stitches, or the subject can remove them with a provided disposable suture removal kit. Subjects will also be asked to undergo venipuncture; all subjects will be asked to have the venipuncture and have the option to refuse. 10ml of blood will be collected for RNA and DNA extraction. Once the skin biopsy is obtained,skin fibroblasts will be isolated, which will be reprogrammed into iPSCs. RPE cells will be derived from the iPSCs. Remuneration: If subjects make a special trip only for the research procedures, they may be reimbursed for travel expenses including: airfare, mileage, parking, and hotel. In order to receive reimbursement, they must provide a copy of the original receipts for those expenses. Reimbursement will not exceed $1000.00.

Clinical Trial Outcome Measures

Primary Measures

  • Number of iPS cells successfully differentiated into RPE cells
    • Time Frame: one year

Participating in This Clinical Trial

Inclusion Criteria

  • Patient must have been diagnosed on the basis of genotyping with a bestrophinopathy. – Patient must be willing to provide a skin biopsy from which we will generate iPSCs. – For pediatric patients, parents must be willing to donate skin biopsies as well. Exclusion Criteria:

  • Children under the age of 5 – Patients exhibiting secondary ophthalmic disorders that are not typically associated with the bestrophinopathies may be excluded.

Gender Eligibility: All

Minimum Age: 5 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mayo Clinic
  • Provider of Information About this Clinical Study
    • Principal Investigator: Alan D. Marmorstein, Ph.D., Professor of Ophthalmology, – Mayo Clinic
  • Overall Official(s)
    • Alan D. Marmorstein, Ph.D., Principal Investigator, Mayo Clinic
    • Raymond Iezzi, M.D., Principal Investigator, Mayo Clinic
    • Sophie J. Bakri, M.D., Principal Investigator, Mayo Clinic

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