One of the most insidious aspects of opioids is that they can change the brain by rewiring its circuitry, which drives addiction. GATC Health, a California-based science and technology company is exploring drugs that may be able to hit the reset button — fixing this faulty wiring and giving people with opioid use disorders and fentanyl addiction a fighting chance to kick the habit.
“We believe we have discovered the core problem of addiction in the brain and have a novel solution that will help opioid addicts recover quicker and with greater benefits,” said GATC’s chief operating officer, Tyrone Lam.
Some 2.5 million Americans have an opioid-use disorder and some 150 people die every day from overdoses of synthetic opioids, like fentanyl, now one of the leading causes of death in the U.S. Often people with opioid use disorders have the desire to quit, but physical cravings derail their efforts, Lam said.
The company, a relative newcomer to the drug discovery space, recently began pre-clinical stage testing on its opioid abuse compounds, which it believes could increase the odds of recovery. It identified the compounds using GATC’s proprietary AI platform, which is designed to speed drug development by identifying which drugs and compounds have the highest probability of success in treating a host of diseases. The company’s interest in opioid treatment came about when it gained access to addiction drug target biomarkers from Liquid Biosciences, an AI-based biomarker discovery company.
“It was a combination of wanting to do good, and also having an opportunity with a really unique data set,” said Ian Jenkins, GATC’s chief scientific officer and co-founder.
Using this information, GATC scientists developed new insights about the roots of addiction and began searching for solutions using its drug discovery system. A company study found that the system can predict drug success with 88% accuracy — a vast improvement over the current industry lead optimization success rate of around 8%. GATC identified three promising compounds, and from those, a lead compound. It is now partnering with Christie D. Fowler at the University of California, Irvine, and Eurofins Discovery, to conduct preclinical testing to determine if the compounds are safe, and how effective they are in reducing opioid use, easing withdrawal symptoms, and preventing drug relapses.
Interrupting a negative cycle
Opioids like heroin and fentanyl trap users in a cycle of addiction by creating dysfunctional brain pathways as the brain tries to cope with overstimulation from the drug. Users also come to depend on stimulation from the drug to maintain levels of brain neurotransmitters, such as dopamine, Jenkins said.
“To fix that we have to have a multiple mechanistic approach to right that ship,” Jenkins said. GATC’s drugs help to bring dopamine levels back to normal while also reversing brain inflammation.
If the compounds pan out, they could offer a better solution than the temporary approach provided by current medications used to treat addiction. Drugs such as buprenorphine (Suboxone or Subutex) and methadone can help people move past substance use disorders, but they also have drawbacks.
“They’re doing great work, but they’re just not enough,” Jenkins said. “Methadone really is exchanging one addiction for another. You’re just replacing that drug with something a little more stable. Although it does do some good, it's not going to ever deal with the core underlying addiction.”
As the U.S. continues to grapple with its opioid epidemic, other addiction-abatement research efforts are also underway. One approach, led by researchers at the University of Houston, is testing a vaccine to interrupt the cycle of addiction by blocking the effects of fentanyl in the brain, eliminating the high that drives people to use the drug, while still allowing other pain drugs to work.
But Jenkins said GATC’s drug development program is the only effort that he knows of targeting the core driver of addiction.
“There needs to be a tool that helps reduce the inflammation of the brain, reduce the trigger of addiction, and help (people) get back into a mood where they actually feel like they have something to live for,” Lam said. “This is the first treatment that I've seen that does all those things, versus basically just replacing the opioid addiction with a lesser form of addiction.”
Hitting the reset button
While much remains to be determined, it’s likely that the GATC opioid treatment would need to be taken over an extended period — a year or two — to support recovery.
“Neurons in the brain grow and they change relatively slowly,” Jenkins said. “Doing something like a one-dose treatment, even though that is possible, may not be the safest route. In some of our test cases, a single dose actually does make a difference, but it's likely that ongoing (treatment) is going to be more effective.
The work GATC is exploring may have broader applications beyond fentanyl and opioid addiction, Lam said.
“We believe that we may have uncovered some secret sauce about addiction in general in the brain, which could have some pretty broad implications for anyone who's suffering from addiction,” Lam said.
Building on what they’ve learned about this mechanism could help find treatments for other substance use disorders, such as cocaine or methamphetamine, and potentially even neurological conditions such as post-traumatic stress disorder, Alzheimer’s disease, Parkinson’s disease and major depressive disorder.
“Our goal is to expand on what we’ve discovered in this research to help a broader patient base,” Jenkins said.
Where to go from here
The company is now hoping to get the backing it needs to move its research to the next level. Its efforts have caught the eye of federal leaders who are urgently seeking a solution to the country’s devastating drug problem.
“Our goal is to expand on what we’ve discovered in this research to help a broader patient base."
Chief scientific officer, co-founder, GATC
“We're having a lot of discussions with federal and state government representatives who have access to funding for research,” Lam said. This includes opioid-abatement dollars reaped from lawsuits filed in an attempt to hold drug companies, distributors and pharmacies accountable for their actions, which helped to fuel the national opioid crisis. Already, the cases have generated billions in settlements to individual states, from companies like Purdue Pharma, Walmart, Walgreens, and CVS Health. States will determine how the money will be used.
“Right now, a percentage of those abatement funds are recommended to be allocated toward research. Of course, that falls right in (our) sweet spot. So, we're speaking with a number of different government entities about what we're doing in order to help that progress,” Lam said.
GATC is also looking for potential partners to carry its drugs toward approval.
“We think we've got something amazing here that can help literally hundreds of millions of people, and we're looking for some really good partners to help bring this out to the market,” Lam said.