A new study in mice lends support to a novel theory that autism symptoms may, in some cases, result from inflammation and cell distress signals. The study grows out of earlier discoveries supported by a Suzanne and Bob Wright Trailblazer Award from Autism Speaks, and its findings support the researchers’ proposed direction for developing new autism medicines.
In their research, Robert Naviaux and his team at the University of California-San Diego, focus on a cellular signaling system linked to both inflammation and problems with cell organelles called mitochondria. Mitochondria are microscopic powerhouses that supply our cells with energy.
More specifically, Dr. Naviaux focuses on the role of adenosine triphosphate (ATP) and related molecules generated by stressed mitochondria. These molecules provoke inflammation. They also stimulate at least 19 types of so-called purinergic receptors on brain cells, Dr. Naviaux says. Some of these receptors, in turn, have been associated with impaired language and social skills.
In their latest work, Dr. Naviaux's team tested the effect of suramin, a well-known inhibitor of purinergic signaling created in 1916 to treat African sleeping sickness. The treatment is not suitable for long-term use as it can produce anemia and adrenal gland dysfunction. Rather, the researchers used it to advance their idea that quieting cell-distress signaling could ease autism symptoms. If so, a related drug might be developed that’s safe to take long term.
In the study, suramin did block cell distress signals and related inflammation in adult mouse models of autism. Their cells began behaving normally and their autism-like behaviors eased away. However, the drug’s effects did not last after it was discontinued after five weeks.
"Obviously correcting abnormalities in a mouse is a long way from a cure in humans,” Dr. Naviaux says. “But we think this approach – antipurinergic therapy – is a new and fresh way to think about and address the challenge of autism. Dr. Naviaux co-directs UCSD’s Mitochondrial and Metabolic Disease Center.
“It’s good to see this additional evidence in support of Dr. Nauviax’s novel research path,” comments Dan Smith, Autism Speaks senior director for discovery neuroscience. “The continued development of novel treatments and transformative ideas are exactly what we hope for from our Trailblazer grants.” Because suramin is not a safe treatment option for people with autism, Dr. Smith adds, we need to stimulate the pharmaceutical industry to develop new options. “Basic research like Dr. Naviaux’s is critical for doing just that.”