One-year pilot study on the effects of nitisinone on melanin in patients with OCA-1B.

Abstract

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.

TRIAL REGISTRATION:

CLINICALTRIALS:

gov NCT01838655.

FUNDING:

Intramural program of the National Eye Institute.

• Authors: David R Adams, Supriya Menezes, Ramon Jauregui, Zaheer M Valivullah, Bradley Power, Maria Abraham, Brett G Jeffrey, Angel Garced, Ramakrishna P Alur, Denise Cunningham, Edythe Wiggs, Melissa A Merideth, Pei-Wen Chiang, Shanna Bernstein, Shosuke Ito, Kazumasa Wakamatsu, Rhona M Jack, Wendy J Introne, William A Gahl, Brian P Brooks
• Journal: JCI insight (JCI Insight) Vol. 4 Issue 2 (Jan 24 2019) ISSN: 2379-3708 [Electronic] United States
• PMID: 30674731 (Publication Type: Journal Article)