Joe Monaco
KU Office of Public Affairs

KU researcher pursuing new treatments for Tourette syndrome

Thu, 05/23/2013

LAWRENCE — Chances are, you know or have seen someone affected by Tourette syndrome (TS), a neurological disorder characterized by involuntary tics like blinking, head-jerking or uncontrolled vocalizations. Depending on the severity of the tics, they can range from a mild annoyance to a dramatic impact on a person’s ability to function.

While some medications have proven useful in mitigating the tics, they often have side effects. This is especially true of antipsychotics, which are effective in treating TS symptoms but come with side effects such as sedation, weight gain and cognitive dulling.

That’s why a University of Kansas neuroscientist is working to find new treatments with fewer side effects for people with TS. Marco Bortolato, an assistant professor of pharmacology and toxicology in the KU School of Pharmacy, is now examining the neurobiological basis of TS with the hope of unlocking the syndrome’s underlying mechanisms.

“While there are some effective medications for Tourette syndrome, there aren’t any universally effective medications, and many of the best treatments have severe side effects,” Bortolato said. “Additionally, the agents currently approved for TS have limited efficacy in treating the conditions often associated with TS, including obsessive-compulsive disorder, impulse-control disorders and attention-deficit hyperactivity disorder, which are often as disruptive to patients as their TS tics. So we’re trying to better understand the pathophysiology of TS to develop better treatments.”

Bortolato’s work is tied to 5α-reductase, the enzyme that converts testosterone into 5α-dihydrotestosterone (DHT).

Much research has shown that DHT is linked to brain neurotransmission and behavior, leading Bortolato to hypothesize that if you can inhibit 5α-reductase, you can limit DHT production and, thus, mitigate Tourette symptoms. Consequently, his research has focused on agents that perform as 5α-reductase inhibitors.

In a 2008 study, Bortolato first identified the involvement of 5α-reductase in TS using animal models. Following that research, Bortolato discovered that finasteride – a 5α-reductase inhibitor already being used to treat male-pattern baldness and prostate enlargement in men – was especially effective in mitigating tics in TS patients. Building on those findings, Bortolato is now leading a larger study that examines 5α-reductase in combination with environmental factors, specifically early childhood stress. In addition, he is also evaluating the molecular mechanisms of action of finasteride in animal models.

Bortolato hypothesizes that the interaction of 5α-reductase genetic variants and early exposure to stress is linked to TS and other associated neurological disorders.

“Ample evidence indicates that TS is likely caused by alterations within the brain circuitry resulting from interactions between genes and environmental factors,” Bortolato said. “We think that, in males, the interaction of 5α-reductase variants and early exposure to stress may lead to increased synthesis of androgens like DHT and other alterations in steroid profile. These changes may impair stress responsiveness and impulse control, thereby facilitating the pathogenesis of TS and other neurological disorders.”

Bortolato’s current clinical studies are funded by a two-year, $150,000 grant from the Tourette Syndrome Association, and they will involve more than 400 adult male subjects. He is collaborating with colleagues from Harvard University and the University of Southern California. His research on animal models is currently funded by a one-year, $45,000 KU COBRE CMADP Pilot Project.

Read more here about Bortolato and his research.


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