TSC, another genetic disorder linked to autism, is caused by mutations in one of two genes, which trigger development of benign tumors in the brain, eyes, heart, kidney, skin, and lungs. About 90 percent of TSC patients have epilepsy, and 50 percent have autism or other cognitive impairments.
The normal function of the TSC genes is to turn off a protein called mTOR, a potent cell-growth stimulator. Animal research shows that rapamycin–an immunosuppressant drug that turns off mTOR–can reduce seizures and abnormal brain enlargement in affected animals, as well as improve learning and memory.
Previous small-scale studies of rapamycin in patients with TSC have shown that it can reduce the size of tumors, but those studies did not look at the drug’s affect on seizures and cognitive symptoms. Mustafa Sahin, a neurologist and scientist at Children’s Hospital Boston, is now planning a randomized trial of rapamycin in 55 patients ages 6 to 21. Scientists will specifically assess seizures, cognitive function, and other symptoms of autism.
Migranka Sur, a neuroscientist at MIT, hypothesizes that synapses in people with Rett syndrome, a disorder characterized by seizures, mental retardation, and motor problems, remain immature but can be chemically induced to mature. “IGF [insulin-like growth factor] and EGF [epidermal growth factor] are two pathways we think can be activated to make synapses mature,” Sur said at the autism symposium. His group recently showed that treating mice with the Rett mutation with a fragment of the IGF protein stimulated synapses, improved motor function, and extended life span.
Scientists in Sur’s lab are now planning a placebo-controlled clinical trial of IGF in girls ages 2 to 10. The drug is already approved to treat children with short stature, so its safety profile is well known.
Scientists are particularly excited about the new drug trials because they target specific molecular processes believed to be at the root of these diseases. “These are not palliative approaches,” said Bear at the autism conference.
While initial trials will focus on these three specific diseases, Bear and others hope that the treatments will prove more broadly applicable. “The hope is that we’ll uncover pathways that are involved in cases of autism with unknown etiology,” said Bear. Even though there may be hundreds of genes affected in different cases of autism, he said, “I strongly suspect that there will be a few key pathways, so drugs that regulate that pathway may have a broad impact.”