Nitisinone shows promise for treatment of oculocutaneous albinism
MedWire News: Results from a study in mice suggest that the drug nitisinone, approved for treatment of hereditary tyrosinemia type 1 (HT-1) in humans, may help protect the skin and eyes of people with a mild version of oculocutaneous albinism type 1 (OCA-1) by increasing their pigmentation level.
People with albinism are at increased risk for skin cancer and eye problems due to their lack of pigmentation.
OCA-1 is caused by mutations in the gene encoding tyrosine (TYR), which is a precursor for melanin. OCA-1A individuals lack functional TYR and therefore produce no melanin, whereas OCA-1B individuals have partially functional TYR and produce some melanin.
Brian Brooks (National Eye Institute, Bethesda, Maryland, USA) and colleagues investigated whether nitisinone, which is known to increase serum concentrations of tyrosine, could increase pigmentation in two mice models genetically modified to have a OCA-1A and OCA-1B.
As reported in the Journal of Clinical Investigation, they found that nitisinone significantly improved pigmentation in mice with the murine version of OCA-1B, but not OCA-1A.
In an extension of the mouse study the researchers also investigated the effect of nitisinone on melanocyte cells cultured from patients with OCA-1A and OCA-1B.
They found that, similar to the results of the mouse study, nitisinone improved pigmentation in cells from OCA-1B, but not OCA-1A patients.
"Nitisinone is approved by the [US] Food and Drug Administration for use in the treatment of HT-1, along with a special, protein-restricted diet," explain Brooks et al. "Recent experience with this compound in patients with a related disorder of tyrosine degradation, alkaptonuria, suggests that it can be safely administered to adults receiving a normal diet without significant systemic complications."
They suggest: "Nitisinone may therefore provide a clinically viable means of increasing pigmentation, and potentially visual function, in patients with OCA-1B."
A pilot study to test the effects of this drug in people with OCA-1B is currently being organized, says the team.
In an accompanying commentary, Prashiela Manga and Seth Orlow (New York University School of Medicine, USA), praised the work of Brooks and colleagues, but cautioned: "Developmental defects due to lack of melanogenesis during embryogenesis are not expected to be correctable in an adult. Instead, correction would need to occur during the appropriate developmental window."
They commented: "Since OCA-1B is a recessive disorder, parental carrier status is usually unknown until a first affected child is born. It is therefore unlikely that we will be able to treat women early enough during pregnancy to affect optic tract development."
Manga and Orlow concede that it may be a viable option in second pregnancies or in pregnancies with an associated strong family history of OCA-1.
By Helen Albert