Laboratory discoveries that increase our knowledge of how the body works occur all the time. But it’s another matter to turn this knowledge into a treatment.

“The process of translating basic science research into a clinical trial is often stalled,” says Boston Children’s Hospital ophthalmologist Carolyn Wu, MD.

Wu is one of the exceptions. Along with Ophthalmologist-in-Chief David Hunter, MD, PhD, and neurobiologist Takao Hensch, PhD, she is in the midst of a clinical trial testing whether a drug—one used for Alzheimer’s disease—can restore vision in patients with amblyopia, also known as “lazy eye.”

Amblyopia occurs when vision fails to develop properly because the brain isn’t processing the input from one eye very well. When a child is young enough, amblyopia can often be cured by blocking the better eye with a patch or blurring it with eye drops, forcing the brain to use the weaker eye. However, this treatment doesn’t work for older patients whose brains are no longer as good at forming new connections, and the weak eye can permanently lose vision.

The trial grew out of Hensch’s work studying amblyopia in mice as a model for understanding critical periods—time windows during early development when the brain forms new connections easily. There’s a critical period for visual development, and Hensch’s lab found that levels of a protein called Lynx1 rise just as this critical period ends. When the Lynx1 gene is deleted in mice, brain activity via the neurotransmitter acetylcholine increases, the critical period stays open and amblyopic mice can regain visual acuity.

Aricept for amblyopia?

As it happens, the Alzheimer’s drug donepezil (commonly known by the brand name AriceptTM) increases brain activity in a similar way, by preventing acetylcholine’s breakdown. Hensch’s tests in mice suggested that it might allow an older child to benefit from the same sort of patching strategy used with younger patients.

“If we catch amblyopia early enough, the patch or eye drops typically work,” says Wu, “but with this medication, we may be able treat older children and adults who are beyond that window by reactivating brain plasticity.”

Originally Hunter and Wu wanted to conduct a randomized trial, giving some patients placebos, but it was unclear how well donepezil could be absorbed through the special gel capsules used to make the treatments look identical. Researching this would delay the trial, so they applied to the FDA to conduct an open-label trial, where every patient would receive donepezil.

“With any clinical trial,” says Wu, “things come up along the way that may not have been anticipated.”

Mounting a donepezil clinical trial

The Investigational New Drug application submitted to the FDA called for every subject to receive a slowly increasing dose of donepezil over a 12-week period, along with patching of the stronger eye. Patients would then be re-evaluated 10 weeks after treatment cessation to see whether improvements in visual acuity were maintained.

But the FDA had questions about the process of splitting donepezil tablets to achieve the different dosages. This meant a $4,000 machine and further delays. Additionally, each tablet would have to be hand-weighed to make sure each portion was exactly the right quantity. Wu and colleagues also had to confirm that the split pills would be stable, which they did by letting them sit for 60 days at varying temperatures.

After two months of additional preparations, the trial began in September 2012 with the goal of enrolling 20 subjects age 8 and older. So far, four subjects have completed the 22-week study, and one more is in the process. Those who completed it have improvements in vision that have been maintained even after the medicine was stopped.

Wu and colleagues are already preparing for a more rigorous 26-week randomized trial that would involve 50 to 150 subjects.

But in the meantime, Wu says, families are asking whether their child can keep taking donepezil once the trial stops, if they’re still improving. Because the medicine is commercially available, the option to use donepezil off-label is open. And Wu is continuing to give the medicine to at least one subject who’s completed the study, to see how much more her vision can improve.

“We pulled up roots from an established position in Japan and moved specifically to Boston Children’s to gain more interactions with clinicians,” says Hensch. “I am grateful to see this vision being borne out through collaboration with Drs. Wu and Hunter to translate our work from bench to bedside.”