Closing the gap in TBI
and concussion care

Despite healthcare seeing incredible advancements over the past decade, the area of concussion and traumatic brain injury treatment has seen little progress. Neuro Rehab Times speaks to Dr. Michael Wyand, CEO of therapeutics company Oxeia Biopharmaceuticals, about the current state of care for TBI and concussions, and how its new treatment could transform concussion care.

Research shows that nearly 30 per cent of US adults have self-reported having had a concussion in their lifetime, however, there is currently no FDA-approved drug therapy for the condition – representing a huge unmet medical need.

Concussions, historically treated with rest, are now recognised as potentially leading to long-term effects like Chronic traumatic encephalopathy (CTE). Associated with repeated blows to the head, CTE can often lead to dementia.

Oxeia CEO, Dr. Michale Wyand, says that today’s standard of care is focused on symptoms and not a cure, and that primary therapy to date is inadequate to address the needs of the millions of people that continue to suffer after sustaining a concussion.

To address this critical gap in care, Oxeia is currently developing a concussion drug, and the treatment’s pilot Phase 2a study has so far seen promising results for debilitating post-concussion symptoms.

“Concussions are an interesting injury because we’ve known about them for a very long time. When you place them within the broader category of traumatic brain injury, they’re considered to be on the milder end of the spectrum,” says Wyand.

“Traditionally, the standard recommendation was rest. You might not know where you are, you might not remember what day it is, you might be staggering and nauseous – but the advice was always, ‘Just rest. Go home, and you’ll be fine.’

“If you went to an emergency room after an accident and had what was deemed a minor brain injury, they’d scan your brain to check for bleeding or a skull fracture. If neither was present, they’d send you home with instructions to rest.

“A lot of people who played sports will remember, if you injured your knee and couldn’t walk properly, it was considered important to go to the hospital for an X-ray to rule out serious damage. But if your brain got injured? You were just told to rest. Part of the issue is that we can’t see inside our skulls. It’s not as obvious as a limp or a cut, so it’s easier to dismiss.

“However, over the past 15 years, we’ve begun to recognise, largely thanks to the athlete population, that these injuries do matter. Repeated concussions can lead to persistent symptoms, which are highly problematic.

“So, now we understand that concussion is something that deserves attention. Our tagline is: rest is not enough. That’s the shift in mindset we’ve been working toward.

“Historically, most of the research and drug development in traumatic brain injury focused on severe cases – and rightfully so, given the serious and often lifelong consequences. But many of the drug studies for traumatic brain injury failed, especially in the severe category. The central nervous system remains one of the last frontiers in drug development, and our understanding of the brain is still evolving. There’s still so much we need to learn to effectively address these injuries.

“As for mild TBI, there hasn’t been much drug development – largely for the reasons I mentioned. We are one of the first companies, we believe, to submit a protocol to the FDA for a Phase 2 study in this space.

“We’ve completed that Phase 2 trial with a small sample, and as far as we know, no one else has reached this stage or beyond.”

The drug, using the hormone ghrelin, has so far shown an 85 per cent responder rate compared to 33 per cent in standard care. According to Wyand, the drug aims to address energy imbalances and oxidative damage in the brain post-concussion.

“We’re working with an endogenous hormone, a hormone that naturally occurs in the body, called ghrelin,” explains Wyand.

“It was first discovered in the late 1990s. One of its primary functions is to stimulate appetite and increase food intake. It’s produced in various tissues of the gastrointestinal tract, enters the bloodstream, crosses into the brain, and binds to specific receptors there.

“Over time, we’ve come to understand that one of ghrelin’s major roles in the brain is maintaining energy balance, what we call energy homeostasis. When it crosses the blood-brain barrier and binds to brain receptors, it helps regulate energy production in the brain.

“It does several key things: it increases ATP production, the brain’s energy currency, and it enhances the function of mitochondria, which are the energy powerhouses of the cells. It also reduces the presence of reactive oxygen species, which are harmful compounds that can cause oxidative stress and damage.

“When someone suffers a concussion, the shockwaves from the impact cause neurons in the brain to fire all at once. In athletes, you can often see this manifest physically, they may tremble, clench their fists, or experience what looks like a mini seizure. What’s happening is their brain cells are firing rapidly and simultaneously, which depletes all available energy in the brain within seconds, like a battery being drained.

“Despite this, the brain continues trying to function, it burns about 20 per cent of the body’s daily energy intake, so it keeps going. But with little energy available, this leads to the production of those damaging reactive oxygen species, which can injure or even kill neurons.

“Our compound based on ghrelin helps by reducing oxidative stress, boosting energy availability in the brain, and promoting regrowth and connections between neurons. This can help restore memory and cognitive function, so it fits very well with what’s going on with a concussion.”

The first human study for the treatment, which took place at the University of Kansas Medical Center, looked at persistently symptomatic patients who had a concussion injury within 28 days.

The results showed that the 85 per cent of responders showed a 20 per cent reduction in symptom severity in areas including cognition, thinking, functional movement, memory and emotion.

Wyand says developing the treatment and finding funding has been challenging.

“One of the things that’s very clear about concussion is that the interest level is extremely high. Even though we don’t see that in the early stage professional biotech investors, in the indication, certainly in the public, there is extreme interest,” says Wyand.

“So it may be that some of those newer strategies for raising money could help us get this next trial done. Because once we get the next trial done, then good data from that will really pave the way for us to continue to raise money for the development.

“We had a meeting with the FDA before we started this trial, and they approved the trial – our next meeting with the FDA will be when we present our next clinical protocol to them after we have raised the funds to do it. So, it’s a matter of getting the right investor.

“I think this is a tremendous unmet medical need so we’re continuing to push and find the right investor.”