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One-year Pilot Study on the Effects of Nitisinone on Melanin in Patients with OCA-1B

2019 Jan 24

Journal Article

Adams, D.R.; Menezes, S.; Jauregui, R.; Valivullah, Z.M.; Power, B.; Abraham, M.; Jeffrey, B.G.; Garced, A.; Alur, R.P.; Cunningham, D.; Wiggs, E.; Merideth, M.A.; Chiang, P.W.; Bernstein, S.; Ito, S.; Wakamatsu, K.; Jack, R.M.; Introne, W.J.; Gahl, W.A.; Brooks, B.P.

JCI Insight






developmental eye abnormalities; melanin synthesis; oculocutaneous albinism (OCA); skin hypopigmentation; UV-induced malignancy

BACKGROUND: Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to hypomorphic mutations in the Tyrosinase gene.METHODS: In this open-label pilot study, 5 adult patients with OCA-1B established baseline measurements of iris, skin, and hair pigmentation and were treated over 12 months with 2 mg/d oral nitisinone. Changes in pigmentation and visual function were evaluated at 3-month intervals.RESULTS: The mean change in iris transillumination, a marker of melanin, from baseline was 1.0 ± 1.54 points, representing no change. The method of iris transillumination grading showed a high intergrader reliability (intraclass correlation coefficient ≥ 0.88 at each visit). The number of letters read (visual acuity) improved significantly at month 12 for both eyes (right eye, OD, mean 4.2 [95% CI, 0.3, 8.1], P = 0.04) and left eye (OS, 5 [1.0, 9.1], P = 0.003). Skin pigmentation on the inner bicep increased (M index increase = 1.72 [0.03, 3.41], P = 0.047). Finally, hair pigmentation increased by both reflectometry (M index [17.3 {4.4, 30.2}, P = 0.01]) and biochemically.CONCLUSION: Nitisinone did not result in an increase in iris melanin content but may increase hair and skin pigmentation in patients with OCA-1B. The iris transillumination grading scale used in this study proved robust, with potential for use in future clinical trials.CLINICALTRIALS: gov NCT01838655.FUNDING: Intramural program of the National Eye Institute.

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