Overview

Aberrant retinoic acid signaling driven by the degenerating outer retina leads to pathological changes to the inner retina. The resulting hyperactivity of retinal ganglion cells leads to further diminution of the remaining vision in those afflicted with inherited retinal diseases. Inhibition of this pathway has led to improved visual function in murine models of retinal degeneration. This can be accomplished in humans with the FDA-approved irreversible inhibitor of aldehyde dehydrogenases, disulfiram.

Eligibility

Inclusion Criteria:

        Age ≥18 years Only those with a clinical diagnosis of inherited retinal degeneration. When
        available, supporting genetic diagnosis form a CLIA approved lab will be further considered
        for inclusion.
        Only one eye per subject should be identified as the study eye. The study eye must meet the
        following criteria:
          -  Best corrected ETDRS visual acuity letter score ≥ 70 (i.e., 20/40 or better) within 30
             days of enrollment.
          -  Goldmann visual field exhibiting constriction of visual fields to 10 degrees centrally
          -  Able and willing to provide informed consent
          -  Willing and able to abstain from alcohol consumption for the duration of the study and
             the 2 weeks preceding it and 2 weeks following the study end point
        Liver function values that fall in the normal range as specified below:
          -  Alanine transaminase (ALT): less than 40 IU/L
          -  Aspartate transaminase (AST): less than 40 IU/L
          -  Alkaline phosphatase (ALP): less than 300 IU/L
          -  Albumin (Alb): less than 50 g/L
          -  Total Protein: less than 80 g/L
          -  Total Bilirubin: less than 30 umol/L
        Exclusion Criteria:
          -  A condition that, in the opinion of the investigator, would preclude participation in
             the study, e.g., alcohol dependence, cardiovascular disease, hepatitis.
          -  Individuals with a history of diabetes mellitus
          -  Individuals with a history of psychosis
          -  Individuals with hypothyroidism
          -  Individuals with hypersensitivity to thiuram derivatives causing rubber contact
             dermatitis
          -  Those on anticoagulant therapy or other medications that may be affected by
             disulfiram.
          -  An ocular condition, other than inherited retinal degeneration, is present such that,
             in the opinion of the investigator, visual acuity might be affected (e.g., foveal
             atrophy, pigment abnormalities, dense subfoveal hard exudates, non-retinal conditions
             such as epiretinal membrane or vitreo-macular traction, vein occlusion, uveitis or
             other ocular inflammatory diseases such as neovascular glaucoma, etc).
          -  History of major ocular surgery within the prior 6 months or major ocular surgery
             anticipated within the next 6 months following randomization.
          -  Exam evidence of severe external ocular infection, including conjunctivitis,
             chalazion, or substantial blepharitis
          -  Participation in an investigational trial that involves treatment with any drug within
             30 days of randomization that has not received regulatory approval at the time of
             study entry.
        Note: study participants cannot receive another investigational drug while participating in
        this study.
          -  Known allergy or hypersensitivity to any component of the study drug.
          -  For women of child-bearing potential: pregnant or lactating or intending to become
             pregnant within the next 12 months. Women who are potential study participants should
             be questioned about the potential for pregnancy. Investigator judgment will be used to
             determine when a pregnancy test is needed.
          -  Participants who expect to move out of the area of the clinical center during the 8
             months of the study