Astrocyte Pharmaceuticals has achieved two significant milestones in developing the first potential pharmaceutical treatment for concussions, dosing the initial patient in a Phase 2 clinical trial while securing $3 million in NIH funding to advance an oral formulation of its investigational drug AST-004.
The clinical-stage biotechnology company announced that it has begun dosing athletes in its Phase 2 STARFAST (Study of TBI/concussions in Australian-Rules Footballers receiving AST-004) trial, conducted with players from the Adelaide Football League in Australia. The study represents the first human trial of a drug specifically designed to protect the brain from concussion damage.
Breakthrough Neuroprotective Mechanism
AST-004 stands as the first drug to demonstrate in preclinical studies the ability to protect the brain from harmful effects of both mild and severe brain injuries. The compound functions as a selective agonist of adenosine A1 and A3 receptors, designed to support brain recovery by enhancing mitochondrial energy metabolism in glial cells following injury.
"The world has searched for a way to reduce the brain damage caused by concussions – and now we're seeing that possibility with AST-004," said Theodore Liston, Ph.D., Vice President of Research at Astrocyte Pharmaceuticals. "In our early research, the drug consistently protected the brain in multiple models of concussion and head injury."
In preclinical models, AST-004 has demonstrated the ability to reduce tissue damage, brain swelling, and biomarkers linked to neuroinflammation and cellular damage. Two Phase 1 clinical studies involving 80 healthy volunteers have successfully established the drug's safety and tolerability profile.
Phase 2 Trial Design and Objectives
The STARFAST trial offers a unique clinical setting to evaluate AST-004's therapeutic potential. Male and female athletes diagnosed with sports-related concussions on game day will receive either intravenous AST-004 or placebo within 6 hours of the injury. The study design capitalizes on evaluating single, well-characterized concussions in athletes not routinely exposed to repetitive sub-concussive impacts.
This absence of confounding factors creates an optimal trial environment to assess whether AST-004 can mitigate acute injury effects and support more complete and timely recovery. The study will measure safety parameters, speed of symptom recovery, and biological markers in blood that indicate brain response to injury.
Expanding Access Through Oral Formulation
The newly awarded $3 million grant from the National Institute of Neurological Disorders and Stroke (NINDS) will accelerate development of an oral tablet formulation of AST-004. This advancement aims to make the treatment available anywhere concussions occur – from sports fields and arenas to roadsides and battlefields.
"There are millions of people around the world who suffer traumatic brain injuries and concussions each year – athletes, accident victims, and military personnel among them – yet there are no approved treatments," said COL (Ret) Dallas C. Hack, M.D., M.P.H., Advisor to Astrocyte Pharmaceuticals and former Director of the U.S. Army Combat Casualty Care Research Program. "The ability to deliver a simple, safe, oral neuroprotective tablet at the time and place of injury could revolutionize how we treat concussions and dramatically alter short- and long-term outcomes for patients."
Addressing an Unmet Medical Need
The development of AST-004 addresses a critical gap in concussion management. Despite millions of people suffering concussions annually in contact sports and everyday settings, no approved treatments exist to protect the brain from damage. Many patients face long-term consequences including memory issues, mood changes, sleep problems, and increased risk of depression and dementia.
AST-004 is being developed not only for concussion but also for stroke, traumatic brain injury, and Alzheimer's disease. The compound's mechanism of preserving and protecting brain function at the cellular level positions it to limit both short and long-term damage following head trauma.
"Parents, coaches, and communities have been waiting for a real breakthrough – something that doesn't just diagnose or monitor concussions, but actually helps the brain recover," said Dr. Liston. "That's what we believe AST-004 can offer, and these milestones take us one step closer to making that vision a reality."
Astrocyte Pharmaceuticals is advancing both intravenous and oral formulations to address the need for timely intervention in hospital and non-hospital environments, potentially transforming the standard of care for one of the most pressing health concerns affecting athletes, military personnel, and the general population worldwide.
