UCLA's lab work leads to drug development

The GAD therapeutic originated at UCLA from an unexpected convergence of studies in neurobiology and immunology. In the late 1980s, the laboratory of Dr. Allan Tobin, who is now director of UCLA's Brain Research Institute and Eleanor Leslie Chair in Neuroscience, was involved in isolating genes that were thought to be important in brain development and neurological diseases.

Graduate students Daniel Kaufman and Mark Erlander, working with Tobin, isolated the gene that makes GAD, which creates an important neurotransmitter in the brain. At that time, it was known that although GAD was primarily made in the brain, it was also made in the pancreas cells that secreted insulin.

Several years later, Kaufman came to the realization that the autoimmune response that causes type I diabetes may be due to the immune system attacking the GAD protein in the insulin-producing cells in the pancreas. With this knowledge, he and Tobin developed a GAD diagnostic test to identify individuals who were developing type I diabetes based on antibodies in their blood that recognized GAD.

Later, Kaufman, then in his own laboratory at the UCLA Department of Molecular and Medical Pharmacology, along with Dr. Jide Tian, searched for ways to help the immune system tolerate the GAD protein, which would circumvent or inhibit the autoimmune attack. The team reported in the journal Nature in 1993 that by treating young diabetes-prone mice with a small amount of the GAD protein, the immune system learned to tolerate the protein, and the autoimmune response that leads to type I diabetes never developed in these mice as they grew older.

In another study published by Nature-Medicine in 1996, the UCLA team developed a GAD-based drug to inhibit the autoimmune response after it had already begun to attack the insulin-producing cells. Kaufman and Tian showed that even after the type I diabetes disease process had started in diabetes-prone mice, its progression could be inhibited by treatment with GAD.

With this proof-of-principle in mice, UCLA licensed the technology to Diamyd Medical for clinical development. UCLA recently was issued the patent on the GAD gene.