Researchers aim to treat chemotherapy side effects without opioids
Researchers at the University of Arizona are developing a compound that would be used as an alternative to opioids in treating the pain of chemotherapy.
The ongoing opioid crisis has recently been brought to light when Purdue Pharma L.P., the makers of the prescription painkiller OxyContin, filed for bankruptcy in September of this year, according to a report from the Associated Press.
The pharmaceutical company filed for bankruptcy days after a tentative agreement was made with suing state and local governments.
Lawsuits asserted that Purdue Pharma purposely sold “OxyContin as a drug with a low risk of addiction despite knowing that wasn’t true,” according to the same report.
Rajesh Khanna, professor of pharmacology at the UA College of Medicine – Tucson, described how opioids become problematic.
“Opioids have a slew of problems,” Khanna said. “So, you take some and get some relief. You take more and get relief, but after a while, you develop tolerance and dependency. So you need to take more to have the same pain relief, but also, in some cases, it also exacerbates and elicits upon opioid-induced hyperalgesia, which just means basically opioid-induced pain.”
Khanna is also the co-founder of Regulonix, the company that received a grant of $341,528 to pursue this research, according to a College of Medicine press release.
IIn an attempt to stray away from the use of opioids to combat pain, Khanna and his team are seeking an alternative.
“So there’s a big push by the country’s governing bodies for research,” Khanna said. “And the way they’re doing it is putting in an influx of money to fund education and research at various levels to educate both physicians and the users about the problems of opioids. But also at the research level, to come up with new drugs that are bypassing this opioid pathway so you don’t need opioids and can have the same amount of pain relief with something else, and this is where our research in the lab, and particularly through our company called Regulonix.”
According to Khanna, Jun Wang, Ph.D., assistant professor of medicinal chemistry-pharmacology and toxicology, came to him with a series of early leads that eventually became the series of compounds they are currently working with.
“So we have a compound that is selected for a particular kind of channel that is a hot target for Pharma. It’s called the T-type calcium channel,” Khanna said. “We have shown efficacy in pre-clinical rodent studies, showing reversal of pain by these molecules in a rat model of chemotherapy-induced pain.”
Dr. Wei Wang, co-director of the Arizona Center for Drug Discovery and professor of pharmacology and toxicology, described one of the numerous challenges with developing these compounds.
“It takes 10-15 years from scratch to the market,” Wei Wang said. “But for drugs targeting the brain, it’s even longer because a lot of molecules cannot cross the blood-brain barrier.”
Wei Wang also stressed the high risk involved when dealing with compounds meant to target the brain.
Some toxicities can take as long as 10 years to be found. This is because previously unfound toxicities can appear when more people are exposed to the drug, according to Wei Wang.
In an email, Wei Wang described the basic overall process for drug development as follows:
“1. Target identification 2. Assay development and hit identification 3. Structural modification/structure-activity relationship (SAR) study 4. Preclinical studies 5. Phase I clinical studies 6. Phase II clinical studies 7. Phase III clinical studies 8. Approval and launch.”
Some faculty in the department of pharmacology have compounds within Phase I clinical trials. Some are still in earlier stages. Wei Wang’s team, along with Khanna’s, have come up with around 10 compounds, according to Wei Wang.
Wei Wang pointed out the necessity for more medicinal chemists to speed up the process.
A possible idea from Khanna suggested the combination of their drug with a certain level of opioid that doesn’t yield toxicity or side effects.
“You take a lot of opioids, you have a lot of problems. You get pain relief, but you also get many bad side effects,” Khanna said. “What if you decreased your opioid intake to a level where you don’t get any side effects but you also don’t get any pain relief? Not a good thing. But now you add a little bit of our compound with a subtherapeutic dose of morphine and now you have pain relief.”
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Within the context of the opioid crisis, research like this becomes more and more necessary.
“Despite the numerous side effects associated with opioids, they surprisingly continue being approved,” Khanna said. “Now, until we come up with another class of drugs that are non-opioid in nature, this is going to continue … unless we as a company [Regulonix] and we as a pain group at the University of Arizona discover a new class of drugs that bypass the opioid system.”
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