A quest for new therapeutics

By Sally McMahon

Linda Dwoskin, PhD, professor and associate dean of research at the University of Kentucky College of Pharmacy, is leading research on methamphetamine use disorder and working to develop a medication to treat the disorder. We talked to Dwoskin recently about what it takes to develop treatment options and how she works with the healthcare community to develop options that are appropriate for patients. Below are the highlights.

Medical News: What piqued your interest in finding new therapeutics to help wean people with methamphetamine use disorder off the drug?

Linda Dwoskin: From the time I was a child, I have been interested in how the brain works and how the brain controls behavior. I pursued an academic career with those interests as the framework, becoming a neurobehavioral pharmacologist.  

As an undergraduate at Syracuse University, I became interested in substance use disorders and I followed that path in graduate school and was awarded as a graduate student trainee position, a National Institute on Drug Abuse (NIDA) T32 Training Grant, while at the University of Minnesota in the Department of Pharmacology. During my graduate training, I worked on opioids and hallucinogens.

When I moved to my postdoctoral position at the University of Colorado Health Sciences Center, Department of Pharmacology, I began to work in earnest on psychostimulants including cocaine and amphetamines and understanding how they alter brain neurochemistry and behavior, also with support from NIDA.  

I continued this work into my faculty position at the College of Pharmacy at the University of Kentucky.  As a faculty member in a college of pharmacy, my research became more applied and focused on drug discovery and addressing unmet clinical needs.

Specifically, I have been working for about the past 20 years to discover a therapeutic to help those with methamphetamine use disorder, especially since there are no FDA approved therapeutics for those seeking to quit taking methamphetamine. 

MN: What does it take to develop new treatment options?

LD: Developing a new treatment for methamphetamine use disorder takes a team of scientists, as there are many steps in the process which require many different types of expertise.

On our team, we have medicinal chemists who design and synthesize the compounds that may become the sought after therapeutic. We have pharmacologists who evaluate the compounds in assays to determine if the compounds hit the target, have the desired properties and not untoward effects from off-target interactions. Scientists with pharmacokinetics expertise evaluate the compounds for their ability to reach the target in the brain at appropriate therapeutic concentrations or levels when the compounds are administered to the individual by various routes of administration. Also, behaviorists evaluate the efficacy of the therapeutic effect to make sure that the compounds work as predicted based on their desired properties.

Each of the principal scientists with expertise in the different areas is supported by a team of investigators including graduate students, postdoctoral fellows and technical staff who are critical to the team. 

Importantly, as part of our team we have Program Officers at NIDA, who also provide input and consultation on the direction of the project to identify a new therapeutic. As the team learns about how the compounds work, we modify the compounds with the goal of obtaining greater potency at the target, lesser potency at other sites in the body, low or no toxicity, and good properties in terms of druggability, so that they could be developed into a therapeutic.

Once we have the optimal compound and several backup compounds, typically contract research organizations that are approved by the FDA synthesize the compound in large amounts as a human dosage form, evaluate the potential toxicity in detail, and sometimes help to prepare the Investigational New Drug (IND), which is submitted to the FDA for review and approval to evaluate the optimal compound in human clinical trials. 

If the compound has the desired effects in human trials, then the compound can be commercialized for market and available to people to treat them for methamphetamine use disorder.  

MN: How do you work with the healthcare community to develop treatment options that are appropriate for patients?

LD: We meet with members of the healthcare community at local levels and at national and international conferences.

At local levels, members of the healthcare community serve as faculty at the university and we interact with these faculty members regularly through informal discussions and at more formal meetings on substance use disorders.

At the University of Kentucky, substance use disorder is designated as a priority research area (the Substance Use Priority Research Area, SUPRA). The university administration is investing in this area of research and SUPRA with the goal of preventing and reducing the burden of substance use disorders through conducting and translating multidisciplinary and innovative research to inform clinical services, training, public health practice and policy.

SUPRA establishes and recognizes our network of investigators from basic science to clinical science to community and population outcomes. SUPRA holds meetings where we interact and discuss the issues around substance use disorders.  SUPRA’s investigators also attend national and international conferences, for example the College on Problems of Drug Dependence (CPDD), were we network with investigators involved in basic and applied clinical research on substance use disorders.   

MN: How long before a person suffering from methamphetamine use disorder can get the prescription drug your team is working to put on the market?

LD: This is a difficult question to answer because the answer depends on the outcomes of both the basic research to identify the potential therapeutic compound and the clinical research showing that the compound has both safety and efficacy in humans. My best guess for the fastest the therapeutic would reach the market is four years if the FDA agreed to fast track the medication. Such a medication is clearly needed now, but carefully controlled clinical studies are required before the medication would reach the market and available to patients.

MN: How do letters and calls from family of people suffering from methamphetamine use disorder impact your work?

LD: Letters and calls from the families of those suffering have a great impact on me and my research team. These communications make it personal, keep us focused, and drive us towards success. They help us to keep motivated to continue to seek a therapeutic even at times when we are disheartened by experiments that fail and when we take a wrong turn and must correct the course of our work and try again.


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