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Antibody blunts heroins lethality, paving the way for a promising new therapy

A monoclonal antibody that targets heroin is effective in blocking the psychoactive and lethal effects of this drug of abuse in mice — offering a new strategy for heroin addiction and overdose treatment, according to a new study from Scripps Research.

In the study, published on October 6, 2022 in ACS Central Science, the researchers isolated several distinct variants (or “clones”) of antibodies that bind tightly to heroin and its major metabolites. They found that one of these monoclonal antibodies was remarkably effective at blocking heroin’s painkilling effect, as well as its effect in slowing breathing and heart rate — the cause of overdose deaths.

The results also suggested that heroin itself is the best target for such therapies, whereas researchers in the past have targeted heroin’s two major metabolites, morphine and 6-acetylmorphine.

The use of monoclonal antibodies is often called a “passive” vaccine strategy. Active vaccines against heroin, which use immune-stimulating proteins that mimic heroin or its metabolites to elicit the patient’s own antibodies, have so far not been effective enough for clinical trials.

“Our findings suggest that a monoclonal antibody-based therapy will be more effective than a vaccine and should be targeted to heroin itself rather than its psychoactive metabolites,” says study senior author Kim Janda, PhD, the Ely R. Callaway, Jr. Professor of Chemistry, and director of the Worm Institute for Research & Medicine at Scripps Research.

The U.S. Centers for Disease Control and Prevention (CDC) has estimated that there were roughly 108,000 drug overdose deaths in the country in 2021, a jump of nearly 15 percent from 2020’s figure. The great majority of these deaths involved opioids such as heroin and fentanyl. Current treatments, which include the small-molecule drug naloxone, are far from being completely effective, and heroin-use relapse after treatment is common.

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