One in seven Americans — in cases that range from child abuse, domestic abuse, and sexual assault to the trauma faced by soldiers, police, and firefighters — will battle post-traumatic stress disorder at some point in their lives.
Current medicines work for only half of the 24.4 million Americans who suffer PTSD at any given time and they see only 30 to 60 percent improvement in their symptoms, said Anantha Shekhar, professor of psychiatry, pharmacology and neurobiology at the Indiana University School of Medicine in Indianapolis.
But a startup company called Anagin, a recent recipient of a $692,706 Phase I Small Business Innovation Research grant from the National Institutes of Health, is on a mission to revolutionize PTSD treatment.
Co-founded by Shekhar and Yvonne Lai, a senior scientist with IU’s Department of Psychological and Brain Sciences in Bloomington, Anagin is developing drugs that block the target mechanism of PTSD without triggering others that cause crippling side effects. Those include agitation, irritability, sexual dysfunction, drowsiness, memory and motor skill problems and addiction, he said.
“Current medications work on brain chemicals such as GABA and glutamate, which affect many brain functions such as thinking, motor coordination, memory and alertness,” said Shekhar, who also directs the Indiana Clinical and Translational Sciences Institute.
“Since (our) drugs do not directly block the normal brain chemical message mechanisms, they will not cause sedation, memory problems and motor difficulties such as balance, walking and driving. So we think the effectiveness of these medications will be much greater.”
Anagin’s prospects for success are such that BioCrossroads named it a finalist in its New Venture Competition, whose winner will be announced Oct. 14. BioCrossroads is an Indianapolis-based, public-private collaboration that provides money and support to budding life-science businesses in Indiana. Since 2012, the competition has awarded more than $120,000 to nine startups that attracted nearly $5 million in subsequent funding.
Launched in 2013, Anagin is a product of the Spin Up program created by the Indiana University Research and Technology Corp. IURTC brings promising technologies to market by helping IU researchers form startup companies. Spin Up specifically aids companies like Anagin, whose technologies are promising but at early stages of development.
With Spin Up’s help, Anagin has had little trouble getting support from early-stage funding agencies. Along with its NIH grant, Anagin will receive $50,000 in matching funds from Elevate Ventures, a nonprofit organization that provides state dollars to promising, early-stage entrepreneurs who have received funding through small business grants.
“Anagin was funded in its first application to the NIH, which is rare,” said Joe Trebley, who heads startup support and promotion for IURTC and the Spin Up program. “Part of the reason is the strength of the development team. You have two people in Dr. Shekhar and Dr. Lai who are very renowned in their field.”
Another factor is the tremendous market opportunities that Anagin’s drugs, if successful, may provide for future PTSD treatment.
“It’s an enormous market and a critical unmet need in some of our most vulnerable populations,” Trebley said. “We’re talking about drugs that can help a wide variety of people such as veterans, victims of violent crime … any sufferer of PTSD who feels the effects of anxiety, depression or chronic pain.”
The prospect of lower health care costs also is a consideration. According to a 1999 study published in the Journal of Clinical Psychiatry and cited by the Centers for Disease Control and Prevention, the annual cost of anxiety disorders in the U.S. was estimated at $42.3 billion — a figure Shekhar and the CDC view as conservative 15 years later.
“This estimate focused on short-term effects and did not include the effect of outcomes such as the increased risk of other disorders,” the CDC said on a section of its website that lists statistics on the burden of mental illness.
A CRIPPLING DISEASE
Through more than 25 years as a psychiatrist and neuroscientist, Shekhar has seen more than his share of the ravages that PTSD sufferers endure.
“There was a young man who served for two years in Vietnam but has since been isolated from society, depressed and unable to function for 35 years,” Shekhar said. “There was a young woman who was assaulted, developed severe PTSD and then committed suicide within a year. There was a child that was attacked severely by a dog while waiting for the school bus and has not been able to attend school.
“There have been hundreds of patients that I have tried to help with this problem,” he added. “But I have been frustrated with the lack of effective interventions.”
Shekhar’s encounters offer a brief glimpse into a wide window of how PTSD affects everyday Americans.
According to PTSD United, a California-based nonprofit support organization for PTSD sufferers, about 44.7 million Americans — roughly one in seven — either have the disorder or previously struggled with it.
About 24.4 million Americans, a figure nearly equal to the population of Texas, have PTSD at any given time. Although military personnel — particularly after protracted tours in combat zones such as Vietnam, Iraq and Afghanistan — are commonly viewed as primary sufferers of PTSD, figures provided by Shekhar suggest otherwise.
They indicate nearly half of abused children develop some form of PTSD, while 45 percent of domestic violence victims and 36 percent of sexual assault victims suffer the disease. About 30 percent of military veterans deal with PTSD, along with 15 percent of firefighters and 13 percent of suburban police officers.
Women are particularly susceptible to PTSD. According to 2014 study published in JAMA Psychiatry, researchers at Columbia and Harvard universities found that one in nine females — about twice the rate of men — develop PTSD sometime in their life. According to a 2009 study also cited by the CDC, anxiety disorders — which include PTSD, panic disorder, generalized anxiety disorder, phobias and separation anxiety disorder — are the most common class of mental illness.
Shekhar said about 40 percent of PTSD sufferers become “completely disabled” by its symptoms, with 20 percent becoming suicide risks and 60 percent developing drug or alcohol addiction.
“Patients can become extremely withdrawn, avoid society, become unable to work and have severe sleep problems,” he said.
Even when treatment drugs work, the side effects often create other problems.
“With antidepressants, it can be agitation, irritability and sexual side effects,” Shekhar said. “With anticonvulsants, you have sedation, dulling of thinking, motor coordination problems and memory disruptions. With anti-anxiety medications, it involves sedation, motor problems, memory problems and addiction problems.”
With Lai directing early development of Anagin’s lead drug, pre-clinical tests on rats showed that nitrous oxide production associated with neural receptors — a key process in forming fearful memories — can be disrupted without triggering mechanisms that cause side effects.
So far, the drug appears to have no sedative, memory or motor effects, Shekhar said.
“This is the first-ever drug to work on this target in the brain,” he said. “This treatment, if given in the early stages — soon after trauma — specifically disrupts the key molecular step in developing crippling fears and fear memories that are the core problem with PTSD. If the trauma is in the past and PTSD is already fully established, then the treatment also enhances more rapidly overcoming — extinguishing — the symptoms.”
Although other new treatments involving inhibitors, antagonists and modulators of neural receptors are entering the market, Trebley said Anagin’s strategy to specifically target PTSD sets it apart.
“We anticipate that the Anagin platform will significantly disrupt and grow the PTSD market,” he said.
Armed with nearly $800,000 in seed money, Anagin’s next steps involve ramping up its own research and development, and beginning collaborations with Indiana University and Northeastern University-Boston to supplement its efforts. Part of that work involves optimizing bioavailability — the rate and extent to which a drug reaches a patient’s systemic circulation — and other pharmacological characteristics to validate safety and ensure success at the clinical stage.
With IURTC’s assistance, Anagin is seeking patent protection for its drug composition and treatment methods for PTSD and related diseases.
Within four years, Anagin — named after Shekhar’s daughter, Ana, and his wife, Gina — hopes to complete an investigational new drug.
“We just hired our first two employees at this stage, and we are supporting work by several talented researchers in Indiana and across the country,” Shekhar said. “But if successful, we see expanding to more than a half-dozen in the next (development) stage, and then we will scale even further. We see a lot of opportunity in this space.”