To fight the opioid crisis, researchers try to develop a vaccine against addictive drugs

Hannah Furfaro / The Seattle Times

SEATTLE – It’s been almost 50 years since a group of researchers in Chicago made an extraordinary discovery: They had created a vaccine against drug addiction and a first test showed that it could work.

Scientists supplied a rhesus monkey with drugs like heroin and cocaine; he became addicted. But when they injected the monkey with a compound they had developed – a compound designed to cause the immune system to fight addictive drugs as if they were pathogenic invaders – the animal stopped seeking drugs. .

Their discovery, published in the scientific journal Nature in 1974, heralded a new frontier in drug treatment. But despite millions of dollars of research – and decades of studies, including a high-profile but unsuccessful nicotine vaccine attempt – there is still no Food and Drug Administration-approved shot against an addictive substance. .

Scientists at a new University of Washington research center hope that will change soon.

“What I hope to achieve is pretty much every year we’ll start a new clinical trial,” said Professor Marco Pravetoni, who was recently recruited from the University of Minnesota to lead the new Center for UW Medication Development for Substance. Use the troubles. The center, which has raised more than $ 2 million in seed funding, officially opened last week.

The investment comes as the number of overdose deaths in Washington has risen sharply: 1,855 Washingtonians died of drug-related deaths in 2020, up 33% from 1,399 the year before. Nationally, more than 70,000 Americans died from drug-induced overdoses in 2019, according to the National Institute on Drug Abuse, of which nearly 50,000 were linked to opioids such as heroin, fentanyl and prescription drugs.

Public and scientific perspectives on the nature of drug addiction have changed over time. Once viewed as the result of personal moral failure, scientific advancements have shown that addiction is instead primarily due to genetic and environmental influences.

Currently, people seeking help with addiction can take drugs like naltrexone, methadone, and buprenorphine: these often life-changing drugs prevent cravings, feelings of euphoria, or both. For people who are dependent on opioids, drugs like methadone and buprenorphine also ease withdrawal symptoms.

But drugs also have drawbacks. Methadone itself can be addictive. And these drugs have to be taken regularly – every day or so – and require a prescription or a visit to a specialist clinic.

Vaccines, on the other hand, hold lasting and potentially profitable promises that available drugs do not, experts say. Similar in nature to vaccines for disease, addiction vaccines stimulate the body to create antibodies that recognize a drug and prevent or slow it down from reaching the brain. One shot every few months, or once a year, has the potential to seriously ease a person’s path to recovery.

“[Existing medications] does not work for everyone. And a lot of people don’t stay with them for the long term, ”said Rebecca Baker, director of the National Institutes of Health‘s long-term Help End Addiction initiative, which funded Pravetoni’s work. Would the results be better if we had more options? ”A vaccine, Baker said, could make treatment more accessible.

In animal studies, Pravetoni and other researchers have shown that vaccines against a variety of drugs are safe and effective. Today, he and collaborators in New York and New Jersey are conducting the first-ever human opioid vaccine trial in the United States; they plan to enroll around 45 people to test a vaccine against oxycodone, a commonly abused prescription pain reliever.

UW’s new center will build on that research and previous animal studies of other drugs like fentanyl and heroin, he said. But Pravetoni admits he will face the same challenges that have hampered the development of addiction vaccines for decades. Clinical trials in humans are incredibly expensive – Pravetoni estimates it would take more than $ 200 to $ 300 million to bring a vaccine to market – and big drug companies have shown little interest in participating.

“[Researchers] are trained to overcome adversity, “he said.” I’m not giving up. “

rocky path

Pravetoni’s early work involved investigating the mechanisms behind the effects of drugs like methamphetamine and cocaine. He eventually decided he was more interested in drug development and, under the training of Dr Paul Pentel, a pioneer in nicotine withdrawal research, began work on a vaccine against nicotine addiction. .

At the time, an addiction vaccine seemed “extremely close,” as an October 2011 New York Times article described.

The story featured the work of Kim Janda, professor of chemistry and immunology at the Scripps Research Institute in California. At the time, Janda had already spent nearly three decades working on vaccines against addictive drugs.

But a nicotine vaccine has never failed: all clinical trials have failed. Tests have shown that people who received a placebo quit smoking at the same rate as those who received a vaccine.

Janda also studied opioids and tested vaccines on non-human primates. He licensed the technology to biotech company Cessation Therapeutics, of which he is a board member, but did not generate the level of interest from large pharmaceutical companies or private investors he needed to test. its vaccines in humans. Running clinical trials involving people with drug addiction is expensive and logistically difficult, he said, and drug companies haven’t seen a clear path to financial returns.

Pravetoni said several valuable lessons still emerged from this early work. On the one hand, nicotine vaccines appeared to work on a subset of people, raising questions about whether someone’s biology might make some, but not others, good candidates for a vaccine. . The discovery continues to fascinate Pravetoni, who has since discovered that certain biological indicators – like high levels of a particular immune protein – predict who might benefit.

Second, nicotine posed its own set of challenges: Nicotine molecules are small. And because smokers often flood their bodies with nicotine by smoking multiple cigarettes a day, developing a vaccine that generates enough antibodies to notice so many nicotine molecules – then block them – was difficult.

But a vaccine against stronger drugs like fentanyl, which requires a much lower dose to feel the effect, might work better.

“We learned a lot more [about] which is possible, which may not be so successful, “Janda said, noting that he doesn’t expect vaccines to work against all drugs of abuse.” But if there is. enough money to fund these vaccines, and you had the infrastructure to do it, then you could get it going pretty quickly. “

New start

For the past decade, Pravetoni has led a laboratory of scientists in Minnesota dedicated to the discovery of vaccines and other drugs for substance use disorders.

He was interested in opioids because some of them can be effective drugs, but their effects can also be toxic; a single dose could kill someone. “I kind of felt I could have a more immediate impact,” Pravetoni said.

This year, he and a Columbia University researcher launched the first Phase 1 clinical trial of an opioid vaccine. They are studying the safety and effectiveness of the vaccine, which aims to stop the euphoric and dangerous effects of oxycodone. The vaccine is being tested on people who are already addicted and untreated for a substance use disorder; some participants will receive a placebo, while others will receive a low or high dose of the vaccine.

If the vaccine works, Baker said she could imagine it being used by people who are not currently using drugs, such as people in prison or long-term treatment recovery programs who fear relapse at their exit. Overdose after release is a serious problem in Washington: A large study here found that within two weeks of release, formerly incarcerated people are 129 times more likely than the general population to die from a drug overdose .

Pravetoni and his colleagues also have around $ 50 million in funding for a future clinical trial to test a vaccine against fentanyl, and more funds to test vaccines against heroin and other drugs. Pravetoni says he hopes to enroll participants from Washington when these studies are launched.

His goal, he said, is to secure enough funding to pass at least Phases 1 and 2 – to prove that his vaccines are safe and effective – and then to ask a pharmaceutical company to fund the rest.

But Janda’s experience offers a caveat, Pravetoni says. “He’s pretty famous, a pretty important player,” Pravetoni said. “If he hasn’t been able to recruit someone as a business partner, that says a lot.”

Although UW’s new research center will focus on vaccines to begin with, it will likely expand into other new drug addiction therapies, said Jürgen Unützer, professor and chair of the Department of Psychiatry and Human Sciences. behavior of the Washington University School of Medicine. Once the center hires more faculty and staff – Pravetoni is currently its only faculty member – and has the capacity to conduct clinical trials, it envisions it as a translational research hub. Housed inside the Harborview research and training building, the center will help translate the university’s remarkable core science curriculum into practical treatments, he said.

“We could look at other drugs, for example,” Unützer said. “We have other addiction issues like methamphetamine addiction… and there really is hardly any treatment.”

Meanwhile, Janda switched to studying another category of drug treatment: monoclonal antibodies, which are antibodies made in the lab rather than inside the body, and when injected, focus on targeted molecules to keep them at bay. Such treatment works faster than a vaccine and could prevent or reverse overdoses of drugs like fentanyl.

Pravetoni is also working on monoclonal antibodies against fentanyl and says its work shows promise in animals. As with vaccines, the next step is to bring the treatment onto the long track of clinical trials in humans.

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