Biologics Could Make Impact in Treating Substance Use Disorders

Biologics hold great promise for treating patients with drug addictions, and theoretically even drug overdoses. Two Saturday symposia will look at the potential of biologics in treating patients addicted to nicotine, cocaine, and methamphetamines.

“Biologics are like no other type of treatment for substance use disorders and are different from medications,” said Ivan Montoya, MD, MPH, who will lead Symposia 6A and 6B, “Development Biologics to Treat Substance Use Disorders: An Update for Clinicians.” Part 1 will be presented from 10 am to noon and Part 2 will be presented from 2 to 4 pm. Both sessions will take place in Orange Ballroom D, Lower Level.

“The whole approach is about preventing the access of the drug of abuse to the brain. That is important because the mechanisms of addiction are mostly located in the brain. If we prevent the access of the drug of abuse to the brain, we will be protecting it from being stimulated by the addictive properties of the drugs. Eventually what we expect is that the drug of abuse will be extinguished,” said Dr. Montoya, NIDA Deputy Director of the Division of Pharmacotherapies and Medical Consequences of Drug Abuse.

Speakers in the sessions will discuss three types of biologics—vaccines, monoclonal antibodies, and enzymes. No biologics have been approved by the Food and Drug Administration for use against substance use disorders. Still, the potential to make a difference drives research.

The mechanism of action for each of the three types of biologics is different, Dr. Montoya said.

For vaccines, the mechanism is to stimulate the immune system to produce antibodies against the drugs of abuse, just as vaccines are used to ward off diseases such as measles.

“The idea is that when the virus enters the bloodstream, the immune system will recognize it as something external to the body, and fight and kill the virus,” Dr. Montoya explained. “The body recognizes the substance of abuse as a foreign substance and creates an antigen antibody complex, which is a very big molecule that does not penetrate the blood-brain barrier and does not get to the brain.”

The mechanism of action for monoclonal antibodies is to use the actual antibodies to fight the drug of abuse.

“With that, we bypass the immune system and inject the antibody into the blood so the body has the antibody, and when the drug of abuse is in the bloodstream, those antibodies will immediately fight it and prevent access of the drug of abuse to the brain,” Dr. Montoya said.

For enzymes, the mechanism of action is to metabolize the drugs of abuse. One bioengineered enzyme that will be discussed is butyrylcholinesterase, which is 1,000 times more potent than natural enzymes, he said.

“When we use cocaine, we have a natural enzyme that breaks down and metabolizes cocaine,” Dr. Montoya said. “This one is 1,000 more times efficient so that when someone uses cocaine, that enzyme almost immediately metabolizes cocaine and prevents the access of cocaine to the brain.

“Theoretically, the enzymes can be used to treat overdoses, too, because the mechanism of action of this very potent enzyme metabolizes the drug quickly, so if someone has an overdose, the enzyme could be injected to treat the overdose.”

Presentations will look at a phase III trial of a vaccine for cocaine, as well as an enzyme for cocaine. Also discussed will be monoclonal antibodies for the treatment of intoxications for methamphetamine intoxication and a nicotine vaccine that uses nanotechnology, Dr. Montoya said.

“None of the approaches have been approved by the FDA,” he said. “The entire symposium is going to be about investigational drugs. I am very cautious in my statements because no single drug has demonstrated safety and efficacy as determined by the FDA standards.”