Fragile X syndrome is the second leading cause of mental retardation, after Down syndrome. Caused by a defect on the X chromosome, the syndrome affects boys more frequently and severely than girls; one-third of men with Fragile X are autistic and have trouble with communication and social interaction.
There is no cure or specific medical treatment for the genetic condition—at least not yet. Drug companies large and small, spurred by recent discoveries in neuroscience, are now working on possible treatments.
Among the more intriguing companies to enter the hunt is aFraxis, a San Diego startup backed by Avalon Ventures. The company, led by Avalon partner Jay Lichter, is leveraging discoveries from the lab of Nobel laureate Susumu Tonegawa of MIT to develop a pill that might reduce or reverse the brain abnormalities and related behavioral symptoms of Fragile X.
Lichter agreed to talk with me last month about aFraxis, but missed our appointment. His assistant explained that Lichter was dealing with a company emergency; she said his schedule was so jam-packed that he couldn’t speak with me until sometime in March.
Fortunately, my colleague Luke had a conversation with Lichter in mid-December and shared some of his notes with me. So here’s what we know about aFraxis so far.
The company was formed in 2007, the same year Tonegawa’s research in Proceedings of the National Academy of Sciences (PNAS) identified a possible drug target for Fragile X. That target was PAK, an enzyme that affects the number, size and shape of connections between neurons in the brain.
In people with Fragile X, these connections-small protrusions called “spines” on the branches of neurons-are longer, thinner and more abundant than in people without the condition. When Tonegawa inhibited PAK in mice that had been genetically alerted to have the symptoms of Fragile X, the spines became