Scientists Simplifying Science

Dealing with an epidemic

in Reporting from the Lab by

The year 2017 challenged the society with a ‘national emergency’ that led to over 60,000 deaths. Some called it an epidemic – a public health crisis – a war against drugs.  As the struggle to deal with the overwhelming opioid crisis continues, many significant steps are being taken by scientists and healthcare professionals to develop a robust arsenal to help tackle this crisis.

A recent article published in the Journal of Medicinal Chemistry describes the development of an opioid vaccine that produces antibodies against heroin, its metabolites and other commonly misused narcotics such as hydrocodone, codeine, oxymorphone, hydromorphone and oxycodone. The vaccine consists of an opioid conjugated to a larger protein carrier delivered in a liposome-based adjuvant. The antibodies produced in response to immunization with the vaccine successfully sequestered opioids in the blood preventing their penetration across the blood-brain barrier and their subsequent binding to the brain opioid receptors. More importantly, the antibodies did not interfere with current opioid management therapy including methodone, buprenorphine and naloxone.

The vaccine was tested in mice and rats for titers, potency and efficacy. Different doses of heroin ranging from 0.5mg/kg to 50mg/kg body weight were tested via either subcutaneous or intravenous routes, which mimic modes of administration for drug abuse in humans. Based on these analyses, the vaccine generated antibodies that were durable and effective in mitigating the biological effects of opioids even at lethal doses.

Current opioid management involves the use of drugs such as methodone and buprenorphine that are synthetic opiate derivatives. They too, like heroin, bind to opioid receptors, and engender analgesic and euphoric effects. However, due to their longer half-lives (time taken by the body to clear 50% of drug is longer than heroin), the potential for dependency, overdose and abuse, although not exempt, is mitigated. On the other hand, Vivitrol by Alkermes pharmaceuticals is an opioid antagonist that can block opioid receptors from binding to opioids, thereby preventing relapse. Such interventions are currently being tested in combination with novel approaches such as digital therapeutics wherein reSET-O, an app developed by Pear Therapeutics has shown to improve abstinence and program compliance.

This paper provides a unique immunologic approach to combat opioid dependence. These studies overcome some of the previous challenges encountered with the development of opioid-based vaccines namely stable activity against heroin and its metabolites, and broad spectrum utility to remain effective even against other commonly used narcotics. As the vaccine is not effective against fentanyl, tramadone, sufentanil, nalbuphine and other non-narcotics such as aspirin, ibuprofen and acetaminophen, such drugs can be administered in vaccinated patients for pain management. However, investigation on the utility of the vaccine in humans and synergistic studies with other existing opioid management therapies are warranted.

Journal article:

A stable heroin analogue that can serve as a vaccine hapten to induce antibodies that block the effects of heroin and its metabolites in rodents and that cross-react immunologically with related drugs of abuse. Sulima A et al. Journal of Medicinal Chemistry, Dec 2017

Featured image source : Pixabay

About the author:

Radhika Raheja completed her PhD from Cornell University and is currently a Postdoctoral fellow at the Brigham and Women’s Hospital. Her research interests have centered around oncology and neuroimmunology. Among other things, she is striving to effectively communicate scientific discoveries to the community.

 

Edited by: Shreyas Jadhav, PhD

Radhika completed her PhD from Cornell University and is currently a Postdoctoral fellow at the Brigham and Women's Hospital. Her research interests have centered around oncology and neuroimmunology. Among other things, she is striving to effectively communicate scientific discoveries to the community.

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