New OCD drug developed on campus

Josh Hartman - OCD Mouse.jpg

A 60-day-old male mouse perceives the Biological Research and Development Facility’s animal room from his perch on Abel Bult-Ito’s arm. The mouse, identified by the blue tag in his ear, exhibited compulsive behavior. Bult-Ito uses the mice are used as a model for Obsessive-Compulsive Disorder and anxiety in humans. Photo provided by Bult-Ito.

 

A UAF neurobiology professor is patenting a drug that could be used to treat Obsessive Compulsive Disorder, commonly called OCD.

Professor Abel Bult-Ito’s lab recently discovered the drug and published a paper on it earlier this year.

“It was like ‘holy cow,’ we’re using very low doses of this drug and the behavioral effects are just enormous,” said Bult-Ito, who added that the drug showed no side-effects for anxiety or movement and that it worked both short and long-term. “But they’re specific for compulsive-like behavior … that was really exciting.”

Initial tests showed that the drug “was giving very startling results,” according to Swarup Mitra, the PhD student at the head of the study.

“As we were going through we were excited,” Mitra said, “but we didn’t want to be too excited unless all our experiments were completed.”

The Drug

The drug, Desformylflustrabromine or dFBr, was discovered and synthesized in a lab by Richard Glennon at Virginia Commonwealth University. It was then further developed my Marvin Schulte at UAF. Schulte initially gave the idea of testing dFBr to one of his graduate students who happened to be a friend of Mitra.

“We started the discussion about whether we could test this drug on a mouse model,” Mitra said. “I said ‘well, we have a composite mouse model in our lab so why don’t we do that.'”

The drug has shown good results in Bult-Ito’s lab, however, they will continue to do research into the mechanisms of how the drug works and it still has to go through clinical trials in humans. If it passes clinical trials it will go through the process of becoming FDA approved for people to buy, however the success rate of drugs passing clinical trials is only ten percent, according to Bult-Ito.

“dFBr was really just a chance type thing,” Bult-Ito said. “A lot of things happen because of careful planning but sometimes you’re just lucky.”

The Model

During his post-doctoral work, Bult-Ito worked with mice giving him the thought that mice’s nest-building behavior sometimes looked very compulsive. He used this in his design for the OCD.

“Nest-building was really our contribution to the field,” Bult-Ito said.

His model is what is referred to as “spontaneous”—the mice naturally display signs of compulsive behavior. This is different from “induced” models where the mice are given drugs that make them compulsive and then they are given more drugs to treat the compulsions. Bult-Ito said that the spontaneous model is good because the mice are less altered and more natural.

One possible drawback of the model is that the mice don’t show symptoms of anxiety or depression which are often associated with OCD in humans. Bult-Ito had a theory about this disparity.

“Maybe it’s because of the unique situation in people where they can evaluate their own behavior while they cannot control it, that causes anxiety and depression,” Bult-Ito said. “That’s sort of where I’m leaning that this is something unique to people.”

The model uses two tests to determine how compulsive the mice are. The first is to give the mouse a roll of cotton and to see how much it uses to build its nest. The larger the mouse nests is the more compulsive that mouse is. The second test starts with putting a mouse in a room with marbles and wood shavings. The more compulsively the mouse digs around the room the more marbles it will inadvertently bury as it kicks up the shavings.

The researchers used another test to measure anxiety in the mice called an “Open Field Test.” The mice were put in the center of a box and researchers measured the amount of time before the mice left the center and how long they spent exploring the box.

Working with the mice was a favorite aspect of McKenzie Sweeney who is studying behavioral neuroscience

“When I move on and eventually get to decide what I want to do with my lab it’ll be mice research,” Sweeney said.

The Disorder

Disorders like OCD are extremely complex and not well understood, Bult-Ito said stating that 40 percent of people are not treatable right now. He said that focus of his lab will be shifting toward understanding the circuitry the brain and the molecular aspect of OCD.

OCD affects about 1-2 percent of people in the US, according to the National Institute of Mental Health.

“We’re still learning so much about the brain,” Sweeney said. “A lot of people probably don’t understand that these mental health issues don’t have absolutes.”

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2 Responses

  1. I’m sorry, but unfortunately this research has serious problems. The “model” of OCD that Dr. Bult-Ito is using is not a valid analogue for OCD. At all. Mice do not have OCD. They simply can’t. OCD is uniquely human. Non-human animals do not worry the way that humans do. They do not have intrusive thoughts about morality, sex, religion, contamination, harm, order, the way that we do. They do not have what we call “obsessions.” In OCD, it is obsessions that give rise to compulsive urges. Without obsessions we do not have OCD. On this basis alone, the mice model is problematic. Moreover, just because nest building behavior “looks compulsive” is not reason for considering it like OCD. This is a common mistake that people make when they look at the form of a behavior without really understanding the behavior on a functional level. Lots of things might be said to “look” compulsive (playing a video game, for instance, casting a fishing rod over and over. But something is compulsive behavior in an OCD sense when it is done in response to an obsession. Dr. Bult-Ito might wish to re-think his methods and conclusions.

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