More than a decade ago, researchers discovered that cancer was a genetic disease, rendering the defective genes a tractable target for drug discovery -- efforts resulting in the first round of cancer drugs specific to the molecular lesion. Thus began an optimistic new era of cancer cures.
Autism research is at a point where it can start to duplicate the path that cancer research followed: It is now clear that most autism, like cancer, also has a genetic basis, and that while rare forms of both are caused by mutations in single genes, generally many defective genes in a pathway need to work together to produce disease.
Knowing gene names is not sufficient. We must unravel their function. This is the unique strength of the Center for Autism Research and Translation (CART). In autism it is apparent that the mutated genes encode proteins that underlie core pathways of nerve cell communication.
Using an approach similar to efforts that created the first specific curative therapy for cystic fibrosis -- it is now time to determine the biophysical mechanisms by which malfunctioning genes affect the common pathways implicated in autism. Once that is known, it will be possible to design or re-purpose existing drugs to normalize the function of those pathways, and to design and carry-out screens to test for this molecular effect that treats the core elements of the disease. Like cancer therapy, this probably will eventually require a synergistic cocktail of drugs that act on distinct but interacting targets.
The role of the Center for Autism Research is particularly important today since behavioral assays have proven unreliable in drug discovery. These repeated failures have caused major pharmaceutical houses to abandon this area of critical need. There are many reasons pharmaceutical houses have a poor track record, but high on the list is a failure to determine how and where experimental compounds act on the molecular mechanisms of the brain -- which is a unique strength of CART.
We recognize that our program is exceedingly ambitious and requires both novel technologies and unprecedented integration across disparate disciplines from the lab bench to the bedside.
CART also presents a unique opportunity to have a transformational and lasting impact on autism worldwide. We are confident that the program and its goals are feasible because all of the necessary pieces are already in place at UC Irvine.
The university has world-class molecular geneticists, biophysicists, neurobiologists, behaviorists, pharmacologists and clinical researchers, many of whom are already engaged in the study of autism and who are excited by the opportunity to work together in an integrated program.
Traditional National Institutes of Health and private agency grants will continue to play a critical role going forward. We clearly could not have launched such an aggressive campaign without a visionary major philanthropic investment and will not be able to sustain our path without ongoing committed support from the community.
Indeed, our efforts going forward must be highly integrative and entrepreneurial in design as we attempt to duplicate the success of the March of Dimes, a privately funded research effort that defeated another dread disease - polio, and the recent success of the Cystic Fibrosis Foundation,which used a similar approach to what we envision at UC Irvine.