Long translational research road delivers
University of South Florida neuroscientist R. Douglas Shytle's discovery of successful new clinical uses for mecamylamine, a drug once used to treat hypertension, has led to several issued patents on mecamylamine and related compounds. Earlier this month, Shytle, associate professor and research scientist at the USF Center of Excellence for Aging and Brain Repair and the USF Silver Child Development Center, received the university's 2009 "Excellence in Innovation" award.
The award recognizes Shytle's translational research achievements in developing new intellectual property based on clinical research and novel pharmacological discoveries which have led to newly commercialized therapeutics. His most recent success is with a new experimental antidepressant, known as TC-5214, which is covered by USF patents and licensed to Targacept, Inc., a clinical-stage biopharmaceutical company that develops neuronal nicotinic receptor therapeutics. Targacept recently announced the positive results on TC-5214 as add-on treatment in a large clinical trial of adult patients with treatment-resistant major depressive disorder.
While the Innovation Award encourages USF faculty to "think out of the professorial box," for Shytle the road leading "out of the box" and to the success of TC-5214 was long, winding, and strewn with professional and emotional ups and downs as well as moments both serendipitous and Eureka.
"TC-5214 is a unique form of an old Merck drug called 'mecamylamine,' once used to treat severe hypertension in the 1950s," Shytle said. "Because later research suggested that mecamylamine interacted with brain nicotine receptors, we thought it might have a variety of therapeutic effects similar to nicotine, but without the side effects and addiction."
Building on earlier USF clinical research using transdermal nicotine to treat patients with Tourette's syndrome (characterized by body movements (tics) and vocalizations), Shytle, worked closely with USF professors, Archie A. Silver, MD; David Sheehan, MD; and Paul Sanberg, PhD, DSc, to investigate the effects of mecamylamine in Tourette's patients to see if it could help control their symptoms, as observed with nicotine.
"After carefully designing and conducting a large clinical trial in children with Tourette's syndrome in 1999, we were shocked and disappointed to find that the drug had no effect on the tic symptoms," Shytle said. "After reading several reports about how many antidepressants appeared to be interacting with nicotine receptors the same way as mecamylamine did, we decided to go back and take a second look at the data from our clinical trial. And there it was, like finding a gold nugget buried under the sand, clear evidence for an antidepressant effect of mecamylamine, but not for the placebo, in those Tourette's subjects who had depressive symptoms."