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Researchers at the National Eye Institute (NEI) believe that nitisinone may increase melanin production in people with oculocutaneous albinism type 1B (OCA-1B). Patients with OCA-1B experience decreased visual acuity, glare sensitivity and, in many cases, nystagmus, which further degrades image quality.

OCA-1B is the most common form of albinism in the USA and it is characterized by a mutation in the gene that codes for tyrosinase. Tyrosinase breaks down the amino acid tyrosine and is the first enzyme in the pathway to melanin.  

But what is it that makes melanin so important to the development of normal vision? “The truth is we really don’t know,” says Brian Brooks, clinical director at the NEI and lead author of the study.

“There is something – likely something indirect – about the process of making melanin that can also affect the development of the cells of the retina. What’s particularly odd is that the cells of the retina where we see developmental abnormalities clinically do not express the genes for making melanin. It’s the neighboring retinal pigment epithelium and the melanocytes of the choroid that make the melanin,” he explains.

“A fair amount of excellent work has focused on the role of L-DOPA, which is an intermediate in the process of melanin production, which can exert some developmental effects on the retina – but that’s just part of the story.”

In an attempt to find out more, the pilot study followed three women and two men with OCA-1B over 18 months. Each patient was given a two milligram oral dose of nitisinone every day for 12 months, along with six additional months without the drug. Why nitisinone?

“We know from basic biochemistry that one way to stabilize an enzyme is to increase the amount of its starting material or substrate. Nitisinone blocks the degradation of tyrosine, which has the side effect of raising its plasma levels. So, we are using a known side effect of this medication to flood the unstable tyrosinase enzyme with lots of tyrosine (substrate), making it more stable.”

The results? Most participants experienced a slight darkening of skin and hair, and one participant experienced a slight darkening in skin color after sun exposure. Though the team was unable to detect clinically significant changes to melanin production or visual acuity, Brooks remains hopeful that nitisinone could benefit patients with OCA-1B.

“We’re confident for a couple of reasons. One, we saw the effect in mice and, two, it is not uncommon for younger patients to have more ‘plasticity’ in their visual systems. In our pilot study, the patient who showed the most change in his skin and hair melanin was on the younger side,” he explains.

“That being said, I don’t suggest ophthalmologists prescribe nitisinone to their patients with albinism outside of a well-monitored and controlled clinical trial,” warns Brooks. “Although we did not see any serious adverse events in our pilot study, nitisinone can have significant side effects and patients need to be regularly monitored while they are on it.”

Brooks and his team hope to build on this research by running the trial with younger patients. They also hope to look into nitisinone’s efficacy on other forms of albinism.