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

Publication Type
Journal Article
Year of Publication
Adams, David R; Menezes, Supriya; Jauregui, Ramon; Valivullah, Zaheer M; Power, Bradley; Abraham, Maria; Jeffrey, Brett G; Garced, Angel; Alur, Ramakrishna P; Cunningham, Denise; Wiggs, Edythe; Merideth, Melissa A; Chiang, Pei-Wen; Bernstein, Shanna; Ito, Shosuke; Wakamatsu, Kazumasa; Jack, Rhona M; Introne, Wendy J; Gahl, William A; Brooks, Brian P
JCI Insight
Date Published
2019 Jan 24
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.


FUNDING: Intramural program of the National Eye Institute.