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

Development of Induced Pluripotent Stem Cells From Patients With Best Disease and Other Inherited 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

Study Overview

• Status: Completed
• Conditions: Retinal Disease; Best Vitelliform Macular Dystrophy; Bestrophinopathy; Adult Onset Vitelliform Macular Dystrophy; Autosomal Dominant Vitreoretinalchoroidopathy

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.

• Study Type: Observational
• Enrollment (Actual): 48

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children (as well as their parents) and adults with mutations in the gene BEST1 resulting in one of the five bestrophinopathies.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of iPS cells successfully differentiated into RPE cells	one year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Eye Institute (NEI)
• Investigators: Principal Investigator: Alan D. Marmorstein, Ph.D., Mayo Clinic; Principal Investigator: Raymond Iezzi, M.D., Mayo Clinic; Principal Investigator: Sophie J. Bakri, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: June 11, 2014
• First Submitted That Met QC Criteria: June 11, 2014
• First Posted (Estimate): June 13, 2014

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: eye disease; retinal; best1
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Macular Degeneration; Retinal Diseases; Vitelliform Macular Dystrophy
• Other Study ID Numbers: 13-008089; U01EY030547 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: All samples will be de-identified and given a code while stored and used in research. IPD available to other researchers might include age, gender, genetic mutation and diagnosis. No other information will be shared.