Developing improved drugs for post-traumatic stress disorder
Growing up in India, Anantha Shekhar constantly sought new puzzles to solve. Math offered early challenges, but by high school, an interest in biology took root.
"One of the first studies I did was why certain plants open their pores in the day and close them at night—their diurnal rhythm that involves photosynthesis," said Shekhar, an associate vice president for research at Indiana University and executive associate dean for research affairs at the IU School of Medicine.
"Everything in nature has a logic," he said. "All of its systems are built to achieve some sort of biological function. If you understand the function, you can also understand what happens if something goes wrong."
For nearly 35 years, Shekhar has focused on the ultimate puzzle—the human brain—as a practicing psychiatrist. Since 2013, he and Yvonne Lai, a senior scientist with IU's Department of Psychological and Brain Sciences in Bloomington, have pursued an effective treatment for post-traumatic stress disorder, or PTSD, through their startup company, Anagin.
By developing drugs that block the target mechanism of PTSD within the brain without triggering other mechanisms that cause crippling side effects, Anagin aims to revolutionize how the disorder is treated. The company is also pursuing a treatment to reduce the functional deficits experienced after a person suffers a traumatic brain injury.
Current medicines work for only half of the more than 10 million Americans who suffer PTSD at any given time and about 24.4 million who will develop PTSD over their lifetime. And for those people, symptom improvement increases only 30 to 60 percent, Shekhar said. Such treatments also cause side effects such as agitation, irritability, sexual dysfunction, drowsiness, memory and motor-skill problems, and addiction.
"For the last 30 to 40 years, we've been treating the symptoms of psychiatric disorders without understanding the mechanism that causes them," Shekhar said. "Our driving force is to understand the disease mechanism and test what really works and how to address various problems."
To develop something from research that can change someone's life for the better—it's hard to top that.Anantha Shekhar
“Current medications work on brain chemicals that affect many functions such as thinking, motor coordination, memory, and alertness. Because our drugs do not directly block these mechanisms, they will not cause sedation, memory problems, or motor difficulties such as balance, walking, and driving—and should be more effective."
Whereas Shekhar's expertise lies in identifying brain mechanisms of psychiatric disorders, Lai specializes in the molecular science of developing Anagin's drugs.
A Hong Kong native, Lai had an early interest in scientific investigation, shaped by a family illness. When she was 18 and just starting college, her father battled cancer but ultimately lost.
"He died while taking a medicine; we had no understanding of how the medicine worked. So in grad school, I was initially interested in cancer research, but I turned to molecular signaling to better understand what is going on inside a cell. Later on, I merged my passion for cell signaling with drug discovery," Lai said.
"I like to take innovative approaches to drug discovery because a lot of currently approved drugs were discovered years ago or are just minor modifications of older drugs," she continued. "I not only want to come up with new drugs, but I also want to identify novel ways to discover new drug targets. Our combination of molecular signaling, drug discovery, and preclinical and clinical expertise allows Anagin to tackle some very challenging problems in discovering novel therapeutics for neurological diseases."
So far, Anagin has received more than $1 million in local, state, and federal funds to pursue its research objectives. The latest award, a $267,381 Phase I Small Business Innovation Research grant from the National Institute of Neurological Disorders and Stroke, will help Anagin test its inhibitors in a preclinical model of traumatic brain injury.
I not only want to come up with new drugs, but I also want to identify novel ways to discover new drug targets.Yvonne Lai
One of the brightest stars of IU's Spin Up program, an arm of the Indiana University Research and Technology Corp. that helps researchers start their own company, Anagin won the BioCrossroads New Venture Competition in 2014.
In July 2015, Anagin became the first Spin Up company to hire a chief executive officer. In that role, Eric J. Messner guides Anagin's fundraising efforts. Another key role at Anagin is served by scientist and project leader Melissa Haulcomb.
While Anagin's achievements have been satisfying for Shekhar and Lai, their ultimate goal still lies ahead.
"To develop something from research that can change someone's life for the better—it's hard to top that," Shekhar said. "We could do that with our compounds. If we accomplish that, it would be incredible."