A New Universe of Medical Research

Alabama is well represented in this newest field of medical research. Perhaps more promising than the genome is the new frontier of the microbiome — your gut microbes and “all of the bugs that are living in symbiotic relationship with us.”

Dr. Haydeh Payami is relating the microbiome to her longtime study of Parkinson’s disease.

In Birmingham, a researcher wants to discover what specific microorganisms in the stomach cause Parkinson’s disease.

In Mobile, the goal is finding new and better treatments for cancer.

And in Huntsville, they’re trying to create better antibiotics by looking at hot springs, thermal vents at the bottom of the ocean and other extreme conditions.

This is top-tier medical research going on throughout Alabama, and though the projects are not related, they do have something in common — all of these researchers are focusing on the microbiome, which at its simplest is defined as the microorganisms in a particular environment. In humans, that’s primarily bacteria in the gut.

It’s a relatively new field of study, particularly when it relates to complex diseases, says Dr. Haydeh Payami, professor in the UAB School of Medicine Department of Neurology and the John T. and Juanelle D. Strain Endowed Chair.

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“At first, microbiome was pretty much ignored in all of the studies of diseases like heart disease, diabetes, Parkinson’s and Alzheimer’s,” she says. “Everybody first was looking at diet and exercise. Then people concentrated on genetics. No more than 10 years ago, maybe six or seven, literature started picking up on the importance of the microbiome. There’s a whole other world that we’ve been ignoring, and that’s all of the bugs that are living in symbiotic relationship with us.”

Payami now is studying that “whole other world” as it relates to Parkinson’s, but it’s her previous three decades of experience studying the disease that prepared her to do it. She is lead investigator for the NeuroGenetics Research Consortium, which has assembled one of the largest datasets of Parkinson’s patient information in the world.

“When the genomics era rolled in, we were ready to go with a large sample size,” Payami says. “We had data on 2,000 people with Parkinson’s disease and 2,000 without it.”

Payami and her colleagues are putting that data to work with a four-year,      $2.7 million grant from the U.S. Army Medical Research and Materiel Command. They’re looking for a “missing link” between genetic and environmental causes of Parkinson’s disease.

“Hopefully, we’ll find what we’re after, which is microorganisms in the gut that might be the trigger for susceptibility,” Payami says.

At the University of South Alabama’s Mitchell Cancer Institute, the institute’s division director of hematology oncology is continuing microbiome research that he had started at the University of Texas Southwestern Medical Center.

“I was following up on some observations that had been made in Chicago and Paris,” says Dr. Arthur Frankel. “They had studied mice and showed that particular bacteria in the gut of mice predicted whether the animals’ melanoma would respond to immune checkpoint blockade. They found particular bacteria that were in the gut of the mice were linked to whether or not the mice would respond to treatment.”

Dr. Arthur Frankel says his study of “what you eat and the gut bacteria” promise advancements in immunotherapy.

Frankel, who had done immune therapy research and also was seeing a lot of patients, saw that while many patients can respond to immune checkpoint blockades, many did not.

“My interest was whether there was some way we could improve the percent of patients that responded to the therapy,” he says. The two researchers who won 2018’s Nobel Prize for Medicine were doing research that helped him along the way.

“It wasn’t until I adjusted what I was studying based on their discoveries that the role of what you eat and the gut bacteria became clear and important,” Frankel says.

Frankel was working on this with a company named Vedanta, and when he left Dallas for Mobile, the relationship continued, and there has been some success.

“Vedanta has developed a cocktail that, at least in animal models, appears to markedly improve the response to immunotherapy,” says Frankel. Further research shows that it may translate to human response, too.

“The first thing that excited me was that what we find in patients we find in mice and vice versa,” he says. “Many experiments on humans don’t work on mice and vice versa. Surprisingly, this has worked both in the animal and the humans.”

Clinical trials should start within a few months, Frankel says, but more patients are needed.

“We desperately need patients to call us and work with us,” he says. “I have enough funds to analyze people’s gut bacteria from all over the country, but we need to find them. We have a way now that they can ship samples to us that we can analyze. People think they discover things with 10, 20 or 40 patients, but really you need hundreds of patients to know if any treatment or bacteria is good for people.”

Frankel doesn’t expect to find a cure for cancer, but he is happy to contribute in any way he can.

“I would love to tell you that I make major discoveries, but I don’t think that is true,” he says. “I try to help and advance it just a bit. If we can improve the response rate incrementally, I believe that’s saving lives and giving people a better quality of life.”

While Payami and Frankel are doing research on standard microbiome in the human gut, Dr. AJ Singhal, senior research scientist at Huntsville’s CFD Research, is doing something a little different.

Dr. AJ Singhal is researching the microbiome in extreme environments to develop new antibiotics.

“It’s not what you typically talk about when you talk about microbiome,” he says. “We’re talking about the microbiome in extreme environments. We’re looking in hot springs, thermal vents at the bottom of the ocean and places like that. It’s different, but it’s the same. Microbiome is simply the world of microbes. That can be anywhere, on the side of the road or in an intestine.”

Singhal is hoping to develop better antibiotics through his research, and, like Payami, he’s doing this through a grant from the Department of Defense (the research includes developing antibiotics that can fight biological weapons, as well as superbugs). He started the research at iXpressGenes, but last year, CFD Research acquired his division. Both companies are affiliated with Huntsville’s HudsonAlpha Institute for Biotechnology.

Specifically, Singhal and his team are extracting DNA in certain places — soil samples from the bottom of the ocean, for instance — and recreating microbes that haven’t been able to grow in a lab before.

“We take all the DNA out of the soil, then you have access to all the microbes and you can put that DNA into the microbe that will grow in the lab,” he says.  “We’re trying to figure out exactly what the chemistry is and increase the yield of it. The kinds of enzymes there that can synthesize antibiotics are not like anything we’ve seen before.”

Singhal and his team have had about 15 potential “hits,” meaning “potential compounds that may be promising as antibacterials,” he says.

“In general, it is going very well,” Singhal says. “The hypothesis was that since these environments have not been exploited for drugs, there will be a lot of potential there.”

Alec Harvey is a freelance contributor to Business Alabama. He is based in Auburn.

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