Novel approaches and expansive expertise lead to paradigm shifts for autism

Autism can be overwhelming to a family, and we as a nation have begun to bear witness to its very personal costs -- parents’ anxieties, chasing false hope with pseudo-science, and desperately looking for a way to connect with their children. But what if researchers found a way to develop drugs that could result in stopping the disorder? Researchers at the University of California, Irvine Center for Autism Research and Translation, or CART, are determining the mechanisms by which malfunctioning genes affect the common pathways implicated in Autism Spectrum Disorder (ASD) in order to design and carry out cellular screens to test the effects and treat the core defects. By beginning with drugs that can normalize diverse molecular bioassays of diverse ASD samples, researchers at CART are making strides towards developing new targets and drugs that can attack the novel mechanisms for the treatment of these disorders. With over 50 faculty members drawing upon a wealth of diverse expertise and technologies in addition to real-world clinical goals, CART hopes to achieve its vision of “abolishing current and future burdens of autism through discovery and implementation of novel care, so that not a single child is lost to autism.”

The role of CART is particularly important today because pharmaceutical houses have abandoned drug discovery in neurobehavioral disorders since animal models have failed to predict drugs that work in patients. In contrast, CART has developed a step-by-step set of overlapping techniques anchored to the causal genetic lesions in ASD to assure that when behavioral assays are reached, they are securely anchored in the core human disease pathophysiology. The Rapid Discovery Platform (RDP) at CART is an innovative drug discovery effort that unites multidisciplinary research scientists under a common goal of developing an effective pharmaceutical therapy for the core deficits of ASD. Using the RDP process, pharmaceutical companies can quickly and accurately identify targets for therapeutic solutions, saving time, money, and lives. CART’s enhanced ability to determine how and where experimental compounds act on the molecular mechanisms of the brain is a unique strength that maintains its role on the cusp of being able to provide hope in treatment for individuals with ASD.

Current research includes:

  • Pharmaceutical Research: Recently, researchers have found a treatment for Cystic Fibrosis (CF) that was approved by the FDA. CART has set an entirely new paradigm for how to get FDA approval for powerful drug discovery for ASD, similar to the methods used for the CF compound. CART currently has a patent being reviewed on a biomarker that will allow them to do so.

  • Core Research: Understanding the function of genes involved in ASD lies at the heart of CART research exploration. Identifying these genes will provide targets for diagnostic tests as well as model organisms for drug discovery and environmental impacts. Each core area provides a comprehensive, interactive base, each focus providing ongoing discovery information to the others in order to advance the understanding in all researchers.

  • Genomics: Research is conducted to uncover the dysfunction of known ASD genes and looks for new ones in patients by conducting in-depth whole genome sequencing at a speed and accuracy that has not been achievable before. The goal is to identify pertinent malfunctioning genes.

  • Brain and Behavior: The identification of genomic irregularities in structure or cell communication, coupled with the understanding of the implications they have within the neurological system, can translate into preclinical and clinical investigations of new drugs based on biomarkers. Studies including the Autism Diagnostic Observation Schedule, IQ testing, sleep observations and High-density Electroencephalography (EEG) are used to marry key genetic markers with behavioral pattern observations.

  • Biorepository: Researchers acquire or build compounds targeted at consequences and network defects providing genetic material for all other CART research areas to use for testing without the controversial use of embryos, an important advance in iPS stem cell research. These existing human cells or neurons derived from stem cell techniques, such as iPS, can be compared with established mouse models of rare single-gene forms of ASD.

Bio

The University of California, Irvine launched the Center for Autism Research and Translation (CART) through the public-private partnership seeded by generous philanthropic support to carry out a comprehensive research and treatment effort to develop novel effective diagnostics and treatments for Autism Spectrum Disorder. Integrally connected to the large clinical autism center, researchers at CART are currently investigating the neurobiology of ASD with a wide array of scientists working at the levels of gene, molecule, cell, pathway, brain, behavior, and clinical trials. Scientists at CART have the shared goal of elucidating the brain basis for this neuro disorder.

The incredible expertise and rigor of CART had humble beginnings. Director, Jay Gargus was presenting at the National Academy of Sciences where he was speaking at an autism seminar. After his presentation, a man solicited Dr. Gargus with a strong interest in his research. It wasn’t until the man expressed interest a second time, that Dr. Gargus understood the magnitude of his interest. In fact, this audience member was Bill Thompson, the founder of Pimco, and he was incredibly interested in funding the foundation of the CART program. This interest has led to the present success of CART as one of the leaders in autism research.

Website: http://www.autismresearch.uci.edu

Patents

Schmunk, G., Smith, I., Parker, I., Gargus J.J. (2014). Defective Calcium Signaling as a tool in Autism Spectrum Disorders. Patent filing UC2014-805-1.

Tomita, H., Shakkottai, V, Chandy, K.G., Gargus, J.J. (2001) Novel exons of the hSKCa3/KCNN3 gene. Patent number 7,022,480. Issued 4/4/06.

Chandy, K.G., Fantino, E, Gutman, G.A., Kalman, K. and Gargus, J.J. (1997) HKCa3/KCNN3 small conductance calcium activated potassium channel: a diagnostic marker and therapeutic target. Patent numbers 6,165,719. Issued 12/26/2000 and 6,653,100 B1. I

Gargus, J.J. and Estacion, M. (1997) Novel biophysical technique to detect congenital disease. Patent number 6,183,975. Issued 2/6/2001.