Gene Therapy for Gyrate Atrophy

NCT00001735 | Completed Phase 1

• 2 other identifiers: 98008898-EI-0088
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and effectiveness of gene therapy for patients with gyrate atrophy, an inherited condition in which areas of the retina-the inner lining of the wall of the eye-become thin. Over several decades, this degeneration of the retina causes tunnel vision, night blindness, and other vision problems. Gyrate atrophy is caused by a defect in the gene responsible for producing an enzyme, ornithine aminotransferase (OAT), that breaks down an amino acid called ornithine. As a result, excessive ornithine buildup causes the retinal thinning. Currently, this condition can only be treated with amino acid tablets and a very low-protein diet with limited fruits and vegetables and more than 2,000 calories a day from carbohydrates and fats. Some patients cannot maintain this diet, and they need another treatment. One possible alternative is to replace the defective gene with one that functions normally. Patients who have been followed in NEI's Ocular Genetics service may be eligible to participate in this study. Study patients will undergo the following gene therapy procedure:

1. 1.Skin biopsy-A small piece of skin is surgically removed from the patient's thigh.
2. 2.Gene transfer-Skin cells called keratinocytes are taken from the biopsied tissue and grown in the laboratory. The normal gene that produces OAT is inserted into the cells, causing them to produce more of the enzyme.
3. 3.Skin graft-Under local anesthesia, a patch of skin about 2 1/4 inches x 2 1/4 inches is surgically removed from the upper thigh and some of the cells with increased OAT are grafted back onto this area.

Conditions

Gyrate Atrophy

Keywords

Gene Therapy; Graft; Ornithine; Retina; Retinovirus; Retrovirus; Skin; Gyrate Atrophy

Interventions

Gene therapy PROCEDURE

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Elevated serum ornithine level greater than or equal to 200 micro M, as measured by the median of three values obtained monthly for two months prior to the screening visit and at the screening visit. Absence of OAT activity measured by western blot analysis and isolated enzyme activity in skin biopsy samples. Fundus findings indicative of gyrate atrophy as characterized by sharply demarcated circular patches of chorioretinal atrophy. Must be at least 18 years of age. Female patients of child bearing potential must have a pregnancy test done, which demonstrates a negative result and must agree to practice effective birth control for 12 months following study initiation, or until patch removal, whichever comes first. Must sign and date the informed consent and is willing and able to follow study procedures. Patients demonstrates progression of ocular disease due to grate atrophy evidenced by reduction in electrophysiologic testing, visual field testing or progression of retinal findings. Patient has been offered an arginine-restricted diet and is unable to attain ornithine levels less than 200 micro M prior to patch placement. Patient has previously undergone a skin biopsy. Not currently participating in other experimental protocols or therapeutic trials. Does not have a known malignancy or chronic infection yielding immunoincompetence. Patient must be able to maintain follow-up and follow details of the protocol.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Eye Institute (NEI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Brody LC, Mitchell GA, Obie C, Michaud J, Steel G, Fontaine G, Robert MF, Sipila I, Kaiser-Kupfer M, Valle D. Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences. J Biol Chem. 1992 Feb 15;267(5):3302-7.

  PMID: 1737786 BACKGROUND

• Kasahara M, Matsuzawa T, Kokubo M, Gushiken Y, Tashiro K, Koide T, Watanabe H, Katunuma N. Immunohistochemical localization of ornithine aminotransferase in normal rat tissues by Fab'-horseradish peroxidase conjugates. J Histochem Cytochem. 1986 Nov;34(11):1385-8. doi: 10.1177/34.11.3534076.

  PMID: 3534076 BACKGROUND

• Rao GN, Cotlier E. Ornithine delta-aminotransferase activity in retina and other tissues. Neurochem Res. 1984 Apr;9(4):555-62. doi: 10.1007/BF00964382.

  PMID: 6462326 BACKGROUND

MeSH Terms

Conditions

Gyrate Atrophy

Interventions

Genetic Therapy

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Choroid Diseases; Uveal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: April 1, 1998
• Study Completion: October 1, 2000
• Last Updated: March 4, 2008

Record last verified: 2000-03

Locations

US (1)