Bates Students Create Molecule That Could Lead To New Treatments For Memory Disorders, Cancer

Oct 30, 2019

A Bates College professor and team of students have created a molecule they say could be used to treat cancer, Alzheimer's and other medical issues. Their work has been published, and Bates is trying to patent the creation. The molecule, BOBCAT 339, was designed, conceptualized and tested by Bates students. Their professor, Andrew Kennedy, told Maine Public Radio's Morning Edition host Irwin Gratz that it was found to affect a process known as "DNA methylation."

KENNEDY: This is a reaction that occurs on your DNA - doesn't change that code of the DNA, but it changes how the DNA is read. So what we were looking to do was target a family of proteins that essentially inhibit that process. We had genetically removed these proteins from the minds of rodents and shown that they had altered memory, specifically enhanced kind of episodic memory, spatial memory, things that we think of when we think of memory. But there is no drug-like molecule in existence that could do the same thing that these gene knock-out experiments were doing. So we set out to develop one.

That's a hard thing to start at. In the very beginning of drug development, it's a lot like playing battleship, usually just like lobbing things in the middle of the ocean. But every once in a while you get a hit. And that hit is now a signal that you can test out the space really nearby that hit locally. And that's what BOBCAT 339 was - Gabriela Chua, Kelly Wasserman, Haoyu Sun and others in the lab had an idea that they wanted to try this particular molecular structure. They used computational methods to come up with that. And then they synthesized it in a research lab, and then we tested it. And what they found, kind of remarkably, was that it worked, because usually the first try does not work at all.

GRATZ: Talk a little bit about when you say you saw it worked in neurons.

What we're trying to do is use this molecule to affect the biochemical reactions occurring inside the cells. And what that means in the long run is we have this starting point where now we can build off of it in a rather long pipeline through drug development, to go from, 'OK, we have this molecule that works in cells, can we somehow translate that to a molecule like it working "in vivo" - or in a whole animal?' And that drug discovery pipeline varies, but it takes about a decade.

And, you know, lots of things can affect how you have to tweak the molecule. For example, I'm interested in this molecule's effect in memory - needs to get into the brain, which is not trivial. So how do you tweak the molecule to help that occur? It needs to be around for a certain period of time. You generally want to take a pill once a day - you don't want to take a pill every five minutes or once a month, because if there's a problem with the drug, and you have a side effect and you want to take off the drug, you don't want to have to wait 30 days for the effects to go away. And all of that needs to be tweaked. But the important thing here is that we have a foothold to build from.

Yeah, the other thing you wouldn't have at this point is any idea about potential side effects - other effects this molecule might have if it's introduced into into an animal's body.

Precisely. So the nature of the drug itself - it affects how your genes are read, which leads to an incredible potential for its usefulness, but also the incredible potential for other things happening.

But there is potential, especially since you're dealing with the function of memory, to perhaps have an impact on Alzheimer's disease.

That's right. Yeah. So these genetic therapies and gene-targeting therapies that people are developing in neuroscience and across neuroscience are the hope that these types of targets will be more useful for those disorders, because we know that in diseases like Alzheimer's and disorders of memory, it's really how the genes are utilized after learning that seems to be disrupted.

What's been your reaction to the work that has led you to this point?

My reaction is very student focused. This was developed by a group of seven students who are in their early 20s, my research technician, Beth Malachowsky, who does incredible work in the lab. The ideas and the efforts have come from them. And I have a deep faith in young people who are enfranchised with knowledge and responsibility, and the things that they can accomplish in those settings. They've all graduated. So to see them kind of go out into the scientific world, and do other incredible things from my lab, it's been wonderful.

If Bates is granted the patent for this molecule, what exactly will that mean?

The patenting process is important for, basically, ensuring that the idea isn't dropped. It takes about a billion dollars to get a drug from this point to FDA approval. And the only reason anybody - and it would be a large pharmaceutical company - would be interested in taking that up is if they know the property was protected. The reason that we did it was simply to make sure that it was an idea that could be utilized somehow.

Professor, thank you very much for the time. We appreciate it.

Thank you, Irwin.

Originally published 8:50 a.m. Oct. 30, 2019