For the first time, a compound developed at the Milwaukee Institute for Drug Discovery (MIDD) will enter clinical trials at the U.S. Food and Drug Administration.
It’s the first step of testing that, if successful, paves the way for the drug to become a medicine available for patient treatment.
The drug was developed in part by Jim Cook, who has emeritus status but still performs research as an adjunct professor in UWM’s Chemistry & Biochemistry Department. He is also one of the founders of MIDD. Operated under the umbrella of the Chemistry & Biochemistry Department, MIDD advances research and late-stage development of new drugs. The Institute draws its members from various departments across UWM. Researchers have worked on compounds that target asthma, breast cancer, epilepsy, pain, and Alzheimer’s disease, among others.
Developing a drug
Cook is retired, but when he worked at MIDD, he developed compounds that were derivatives of benzodiazepines. That’s the same category of drugs that includes anxiety medications like Valium and Xanax – “Both of which have bad side effects,” Cook said. “They’re sedating, they cause amnesia, and they’re addictive. Now they’re both great minor tranquilizers, don’t get me wrong, but they have problems.”
So, Cook and his colleagues tried to design compounds without those side effects by targeting a different receptor in the brain than the receptors that previous drugs bind to. They came up with several iterations and even licensed some to pharmacological companies, including Bristol Myers Squibb, but for various reasons, the drugs were never brought to full trials.
Then one of Cook’s compounds caught the eye of a researcher named Etienne Sibille, who is the Deputy Director and Senior Scientist in the Campbell Family Mental Health Research Institute at the University of Toronto. Together, they tweaked the design to increase its efficacy until they came up with a formulation that Cook calls “GL-Damonia” – the real name is still proprietary.
The results of GL-Damonia’s tests were promising.
“If you take a young mouse and let it live for six months, what happens is the neurons, the axons and dendrites and synapses (brain cells) start to die. You give them my drug, and they start to grow back, almost immediately to where they were in a young mouse,” Cook said.
Depression can have a similar effect – a depressed mouse will have the same shortened dendrites and axons as aging mice. Sibille administered the compound to mice with depression, and the mice appeared to return to baseline with no depression symptoms.
“That is part of why I think the FDA approved this for Phase 1,” said Cook. “No toxicity, looked good, and neurons were growing back.”
Drug trials and tribulations
Sibille is mainly interested in using GL-Damonia to treat depression and Alzheimer’s Disease, but Cook is hopeful that it may eventually be a treatment for schizophrenia as well. For now, the FDA will look at its effectiveness in treating the first two conditions.
In FDA Phase 1 trials, “what you’re doing is giving the compounds to healthy individuals and making sure there’s no toxicity,” Cook explained.
In essence, Phase 1 is a safety study. The FDA recruits about 20-100 individuals to take the drug and has doctors monitor its impact to determine its side effects and a safe dosage range. If it’s deemed safe, the drug will go on to Phase 2 trials where it will be administered on a larger scale to people who have depression to test its efficacy. If it passes Phase 2 trials, Phase 3 trials see the drug administered to hundreds, if not thousands, of patients to study its effectiveness, monitor side effects, and compare it to commonly used treatments.
If a drug passes all three phases, it can be produced for consumer markets.
But it’s a long shot, Cook warned. Less than 10% of drugs make it through all three phases, and each drug trial is expensive, costing millions of dollars. In addition, drugmakers must pay yearly fees to keep their patents, which can add up when they have filed for patents in multiple countries. It’s why many chemists with small start-up companies will often license their products to bigger pharmacological corporations; those organizations can afford the expenses.
Going through FDA trials means a lot of risk with many roadblocks, but the reward is high. If the drug were to pass clinical trials and become available for the consumer market, “We would make money,” Cook said frankly. “UW-Milwaukee and the UWM Foundation and MIDD would get money.” Royalties from drug sales would be distributed to all inventors, though the lion’s share would go to the drug company that will ultimately manufacture the compound.
But more than the potential payday, Cook and his colleagues stay motivated through the hard work, the bureaucratic red tape, and the numerous roadblocks to success because they want to help people.
“We want to be able to treat patients and feel like we cured somebody,” Cook said. “Most medicinal chemists feel this way.”
Even if their drugs don’t make it out of trial or end up curing patients, researchers can still publish their findings in academic papers. Their work might help another chemist make a groundbreaking discovery that will someday aid patients.
And who knows? Those drugs might just be developed at MIDD.
By Sarah Vickery, College of Letters & Science