Researchers have shown through a study potential of dual-drug therapy against alcohol use disorder – something that is widely prevalent around the world.
The study by UCSF researchers shows that two new molecules can be used to potentially treat alcohol use disorder (AUD), without the side effects or complications associated with current treatment regimens. The approach had highly successful results in mice and may be applicable to other drugs that are often abused.
At the root of the team’s thinking is the idea that AUD and other substance abuse disorders are the result of reinforced pathways in the brain, and that those pathways can be blocked or redirected, ending cravings and habitual behavior.
The study has been published in Nature Communications.
Current pharmaceutical options for AUD attempt to change behavior by making alcohol consumption an unpleasant experience and some require patients to abstain for several days before beginning treatment.
Researchers have been studying the role of the enzyme mTORC1 in the creation of those memories and associations, with the goal of creating an effective drug that can treat the neurological causes of AUD. Ordinarily, mTORC1 is involved in brain plasticity, helping to create connections between neurons that reinforce memory. In previous work, it has been shown that consuming alcohol activates the enzyme in the brain.
Blocking the activity of mTORC1 with the FDA-approved compound rapamycin, used to treat some types of cancer and suppress immune response in transplant patients, can halt cravings in mice engineered for alcohol use disorder. But mTORC1 contributes to a bevy of other bodily tasks related to metabolism and liver function, and people taking it for an extended period often develop liver toxicity, glucose intolerance, and other side effects.
RapaLink-1, a molecule similar to rapamycin, has been developed specifically to keep a tight grip on mTORC1 and completely subdue it. A version of the drug is now being tested in oncology clinical trials.
Researchers designed a second molecule that would latch onto RapaLink-1 or rapamycin—essentially negating its effect—while at the same time being too big to cross the blood-brain barrier.
In other words RapaLink-1 or rapamycin could administered and allowed to circulate throughout the body. Once it had a chance to reach the brain, Rapablock could be given, halting the activity of Rapalink-1 everywhere except in that targeted area.
The tactic worked like a charm when it was tested on the mice.
