DARPA ‘Cornerstone’ program looks to prevent behavioral & cognitive damage from head injuries

The Defense Advanced Research Projects Agency (DARPA) is looking to prevent behavioral and cognitive injuries from occurring within seconds of a blast or impact to the head.

By the end of the five-year “Cornerstone” research program, the Pentagon’s research funding arm wants solutions that allow for repeated prophylactic doses lasting three days that can “provide protection in response to injury at any time within the three-day window.”

“DARPA’s Cornerstone program aims to develop safe and effective integrated countermeasures to prevent brain injury” — DARPA Cornerstone Program

“When an individual sustains a brain injury, it triggers a complex cascade of events that resemble a domino effect,” the Cornerstone program description reads.

“This starts within milliseconds of exposure with an initial response at the cellular or molecular level, followed by an exponentially expanding set of separate, different, and parallel molecular events that can continue for weeks or months, with each path requiring separate treatment.”

Therefore, “Cornerstone aims to target the initial response milliseconds after injury, thereby mitigating the need to treat multiple targets simultaneously.”

Leading the five-year program is Dr. Eric Van Gieson, who has led three other programs in DARPA’s Biological Technologies Office: the Epigenetic CHaracterization and Observation (ECHO) program, the Measuring Biological Aptitude (MBA) program, and the Personalized Protective Biosystem (PPB) program.

“Cornerstone performers will focus on building safe and effective integrated countermeasures–preventing traumatic brain injury from happening at all” — Cornerstone Program Manager, Dr. Eric Van Gieson, DARPA

“Cornerstone aims to improve mission execution and warfighter protection by reorienting the research community to stop what happens at a molecular level in the first few seconds of exposure to blast or impact,” said Dr. Gieson, in statement.

“Through this lens, Cornerstone performers will focus on building safe and effective integrated countermeasures–preventing TBI from happening at all.”

With a background in biomedical engineering, biosurveillance and diagnostics, and defense threat reduction, Dr. Van Gieson joined DARPA as a program manager in August, 2017 “with the goal of using host-based methods to mitigate the impacts of emerging disease threats.”

“Cornerstone aims to target the initial response milliseconds after injury, thereby mitigating the need to treat multiple targets simultaneously” — DARPA Cornerstone Program

DARPA’s five-year Cornerstone program seeks to develop an Integrated Countermeasure and Delivery System that, “when administered prophylactically, protects against behavioral and cognitive injury in the context of blast-or-impact-induced TBI [Traumatic Brain Injury],” according to the program Broad Agency Announcement published on June 2.

According to the program description, Cornerstone research will be focused on the following areas:

1. Identification, optimization, and validation of prophylactic countermeasures that prevent energetically responsive receptors (i.e., targets) from initiating injury response(s) to kinetic insult(s) inclusive of blast or impact
2. Development of Integrated Countermeasures with precise delivery (i.e., spatial and temporal control)

The Pentagon’s research funding arm adds that “Proposed approaches should investigate the prevention of the initiation of harmful signaling cascades at sites of injury, for example, in the central and/or peripheral nervous systems (CNS, PNS) and/or vasculature, and develop countermeasures that can be administered prophylactically (i.e., before exposure) to prevent behavioral or cognitive deficit from TBI.”

Specifically excluded is research that involves:

1. Genetic manipulation of the host in order to aid target engagement or achieve altered
   downstream signaling as a countermeasure.
2. Sole use of in vitro or in vivo model systems that are not accepted as representative of
   kinetic (e.g., blast or impact) injury modes.
3. Treatment strategies focused on interventions delivered beyond five seconds post-injury,
   with preference for pretreatment-based countermeasures that provide a prophylactic
   effect.
4. Reliance on invasive medical procedures for Integrated Countermeasure delivery (i.e.,
   pumps, implants, lumbar or cranial injections).
5. Remotely triggered Integrated Countermeasure delivery (i.e., strategies that require user
   or medic administration post-injury).
6. Approaches not inclusive of real-time and/or highly resolved temporal and spatial
   techniques to validate targeting, safety, and efficacy of countermeasures.

At program completion, DARPA says that “Cornerstone will have developed Integrated Countermeasures (i.e., countermeasure and delivery system) that, at minimum, allow for repeated prophylactic administration, a three-day effective residence time per dose, and provide protection in response to injury at any time within the three-day window.

“Upon kinetic injury (e.g., blast), Integrated Countermeasures should demonstrate spatial and temporal bioactivity necessary to inhibit the initiation of injury processes (e.g., molecular pathway activation) and protect against the development of canonical neuropathological deficits associated with TBI.”

“Cornerstone aims to improve mission execution and warfighter protection by reorienting the research community to stop what happens at a molecular level in the first few seconds of exposure to blast or impact” — Cornerstone Program Manager, Dr. Eric Van Gieson, DARPA

The Pentagon’s research funding arm is looking to save its warfighters from the crippling and cascading effects of a head injury.

If the solutions are successful and ever become more widely available, they could potentially have great benefit for people working in jobs with high risks of head injury.

But will there be any unforeseen reactions that come from tinkering with the body’s natural reaction to brain trauma?

Check back in five years.