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When PBS research scientist Yvonne Lai and IU School of Medicine administrator/researcher Anantha Shekhar joined forces to develop a new PTSD treatment, they did something not always written into the playbook of academic life. They started a company.

PTSD AT THE CROSSROADS

AT A PRESENTATION SEVERAL YEARS AGO BY PBS RESEARCH SCIENTIST YVONNE LAI, ANANTHA SHEKHAR WAS STRUCK BY THE PROMISE OF LAI’S RESEARCH FOR THE TREATMENT OF PTSD. PTSD IS A PERVASIVE AND TROUBLING DISORDER, WHICH HINGES ON AN EVENT OR SERIES OF EVENTS. ITS DEVASTATING IMPACT HAS BECOME ESPECIALLY VISIBLE IN RECENT YEARS WITH THE RETURN OF COMBAT VETERANS FROM IRAQ AND AFGHANISTAN.

 

 

 

An IU School of Medicine researcher, psychiatrist and professor of neurobiology, pharmacology, and psychiatry, who treats a variety of stress-mediated psychiatric disorders—from depression, anxiety, and schizophrenia, to post-traumatic stress disorder—Shekhar grappled with the complexities of psychiatric treatments.

 

PTSD posed a particularly hard challenge. Existing drugs used to treat it are ineffective. Antidepressants are used, but they address the symptoms rather than underlying mechanisms of the disorder. More powerful drugs, acting on glutamate, a chemical neurotransmitter in the brain, have severe and debilitating side-effects. Glutamate is what enables the traumatic memory characteristic of PTSD to form, but it is also critical to learning, memory and motor functions. Until this point, Shekhar explains, “the only way to attack the underlying mechanism of PTSD was to block glutamate and thus affect multiple pathways and functions.”

 

Lai’s research, however, appeared to get around all of these problems. “It was clear,” he says, “that the mechanisms she was talking about could be useful for treating PTSD and other neuropsychiatric disorders.”

 

Shekhar and Lai joined forces. They tested the compound identified in Lai’s research in an animal model for PTSD with positive first results. Then they did something not always written into the playbook of academic life. They started a company—Anagin.

 

More and more, Lai explains, the university and the National Institutes of Health have been encouraging academic researchers to commercialize their work and have put in place the kind of support needed to make it happen. For Lai and Shekhar, that meant “a lot of chemistry, a lot of money, and a lot of support.”

 

They registered the company and enlisted the support of the IU Research and Technology Center program Spin Up, which provides the business know-how, lab and office space in their “incubator” in Indianapolis, as well as the technology, equipment and any other resources needed to transform “a set of concepts” into a commercial venture.

 

“It’s pretty great,” says Lai. “With the help of the IURTC, Joe Trebly, director of Spin Up, and all the connections Anantha has in Indiana, we are assembling a nice team of consultants to cover a whole range of expertise that we need to move this forward.”

 

They also received an NIH Phase I Small Business Innovation Research grant of $692,706, an unusually high amount for this type of grant. They received $50,000 from Elevate Ventures, a nonprofit organization that provides state dollars to promising, early-stage entrepreneurs who have received funding through small business grants. They came in first in the third annual BioCrossroads New Venture Competition, which won them a $25,000 cash prize and other kinds of professional support.

 

 

All of which enables them to proceed with the next steps: enlisting chemists to design molecules.

 

 

“WE ARE ASSEMBLING A NICE TEAM OF CONSULTANTS TO COVER A WHOLE RANGE OF EXPERTISE THAT WE NEED TO MOVE THIS FORWARD"

“We did a lot of work on what we think is an interesting lead small molecule structure,” says Lai. “But the molecule, which worked well, needs some improvement. Collaborating with chemists, we are designing new structures based on our initial leads. We will then test them at IU in animal models. Our goal for the next two years is to use biochemical and cell-based assays to identify a drug development candidate with increased potency and duration of action.” Then if all goes according to their ideal plan, clinical testing of the drug in humans could take place in two to three years.

 

Both Lai and Shekhar have significant experience in pharmaceutical research, and as Shekhar points out, “they complement each other very well.” Lai worked in the pharmaceutical industry in Seattle, Washington for 14 years doing early drug discovery research before coming to IU as a research scientist in 2007. Shekhar has been involved in the testing phase and clinical trials for numerous drugs that have come out in the past 25 years for schizophrenia, depression, and anxiety, including many antidepressants dating back to Prozac and many atypical antipsychotics starting with Zyprexa.

 

Lai also credits Shekhar’s abilities as a visionary national leader in the promotion of translational science, which is making it possible “to collaborate with a lot of people and move our work forward in a constructive way.” He is the director of the IU Center for Translational Science Institute and past-president of the national association for clinical and translational research.

 

So far he is extremely optimistic about the prospects and possible uses of this drug. “The thing that is probably most encouraging to me,” says Shekhar, “is that in theory we could use this drug for brief periods in patients in conjunction with psychotherapy that could lead them to low levels of PTSD symptoms. It doesn’t need to be used for prolonged periods. It could be a six-week course during which they get intensive therapy plus the drug. In that sense it’s not like an anti-depressant. If it works as we predict, it would lead to remission and after that would not be necessary to take.”

 

Further, it’s not addictive. In fact, it could potentially be used to treat other conditions as well—depression, traumatic brain injury, and chronic pain (a condition Lai is working on in collaboration with PBS researcher Andrea Hohmann).

 

Once Shekhar and Lai complete the current project, the company can go on to explore these other uses. With the infrastructure it has in place, it can also partner with people who would need the expertise and structure that is in place to develop other projects.

 

For now the focus is on PTSD. Occurring in close to 1 in 10 or 12 people in the general population, PTSD is even higher in certain groups: According to Shekhar, one in five of those in the military suffer from PTSD, but it is higher in police, firefighters and other crisis workers, as well as in urban vs non-urban populations. PTSD is twice as common in women as men and frequent in children who have had some kind of trauma. Sexual abuse is a big, under-recognized cause and it is estimated that as much as eighty percent of those experiencing sexual trauma may have experienced PTSD.

 

Shekhar estimates that at best about one third of all PTSD patients are effectively treated. More than two thirds are still disabled by it, leading to high incidents of suicide, substance abuse, and depression as a result, some of which occurs in the many misdiagnosed or unrecognized cases.

 

Spin Up director, Joe Trebly, suggests that the market for the new medication may be similarly under-recognized. When Prozac first appeared,” he says, “it met a need that was greatly underestimated.  We think the need for PTSD medication is likewise bigger than we anticipated.”

 

Shekhar and Lai are equally optimistic about the research: “So far it looks like it could be a very positive breakthrough and a new direction for PTSD treatment,” Shekhar contends.

 

 

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