There is no medicine for people who suffer concussions. Instead, they are often told to avoid activities such as reading or watching TV, so their brains can rest and recover. Biotech builder ATAI Life Sciences and Neuronasal are looking to change that.
Pennsylvania-based Neuronasal is working on a treatment that can be given after a patient suffers brain trauma to stop a chain of processes, including inflammation and bleeding in the brain, that leads to concussion symptoms. In addition to short-term symptoms like headache, nausea and anxiety, concussions can also cause long-term effects, such as cognitive impairment and depression. ATAI is investing an undisclosed amount into Neuronasal to bankroll its work.
Neuronasal’s treatment is based on N-acetylcysteine, or NAC, a precursor of the amino acid cysteine that has been used for decades to treat other ailments. The U.S. Army has tested it in soldiers injured by explosions, finding in a 2013 study that soldiers who received NAC within 24 hours of their injury had an 86% chance of clearing their concussion symptoms compared to 42% of those who took placebo. But the soldiers had to take very high doses of the NAC pills to get the drug across the blood-brain barrier.
“[This is] more than you can use in the general population, because you run the risk of having unacceptable side effects, like dizziness and nausea—the last thing you’d want in a cohort of concussion patients,” Neuronasal CEO Thomas Bradshaw told FierceBiotech.
Giving NAC intravenously rather than orally allows for “slightly lower doses,” the company says, but requires patients to stay in the hospital for several days. Neuronasal’s technology solves both problems by delivering drugs to the brain via—you guessed it—the nose. ATAI and Neuronasal hope to show that NAC can treat concussion symptoms with a “multilevel approach.”
“When you have a mild traumatic brain injury, you’ve got a bunch of things going on. The first event is a physical insult to the brain. If nothing else happened, it would probably result in relatively mild damage,” Bradshaw said. “But what is caused by [the brain] banging around is a biochemical cascade. Glutathione levels go down and you get microbleeds and swelling … when you have microbleeds, you’re having a reaction to that as well."
A derivative of cysteine, NAC is involved in synthesizing glutathione, an antioxidant that plays a role in preventing damage to cells after an injury. In concussions, increasing glutathione levels could protect brain cells from reactive oxygen species, which are oxygen-containing molecules that react easily with other molecules and can damage DNA, RNA and proteins.
Neuronasal is testing the intranasal delivery of NAC in a pilot study slated to end in the first quarter. Then, it will move the treatment into a phase 1 study, which will wrap in 2021. The goal is to show that intranasal NAC can boost levels of glutathione in the brain. The study will also look at how glutathione increases in different parts of the brain such as the regions responsible for balance or for processing visual information.
“There is a noninvasive, MRI-based way to monitor an increase in brain glutathione. If we can increase brain glutathione from the introduction of intranasal NAC, then that’s a very positive way for us to go into phase 1 and phase 2 proof of concept,” Bradshaw said.
If all goes to plan, it could become a treatment people can take soon after a suspected concussion: “It’s a safe drug. If we’re able to show efficacy, we won’t have to worry about giving it to people who may or may not have had a concussion to stop potential secondary damage,” Bradshaw said.
What’s more, the intranasal approach might lead to the resurrection of NAC in other diseases.
“NAC has been tried for a couple other indications and shown no efficacy. High doses of oral NAC were tried in a trial for Parkinson’s and they showed no increase in brain glutathione,” Bradshaw said. It could also be useful in intracranial hemorrhage, or bleeding inside the skull, including certain types of strokes.
Neuronasal is just the latest project for mental health-focused ATAI. CEO Florian Brand founded the Berlin-based company alongside Christian Angermayer and Lars Wilde to "spearhead the renaissance of psychedelic medicine and to incubate innovative therapeutic approaches with the ultimate goal of curing mental health disorders," Brand said via email.
"To date, ATAI has raised more than $90 million and our $43 million series B funding round in March 2019 was the largest-ever private financing round for a psychedelic medicine biopharma company," he said.
ATAI has backed companies like Compass Pathways, which is developing the psychedelic psilocybin, and Perception Neuroscience, which is working on a ketamine-like drug, both for the treatment of depression. It has also set up a joint venture with Cyclica dubbed Entheogenix Biosciences that's using artificial intelligence to design new medicines based on psychedelics.
"EntheogeniX will expand access to emerging mental health therapeutics by first creating shorter-acting psychedelics (helping therapists treat more people) and then potentially removing hallucinogenic effects entirely (which could allow those with otherwise disqualifying contraindications to access the benefits of psychoactive compounds)," said ATAI Chief Scientific Officer Srinivas Rao, M.D., Ph.D., in an email.