F.From curing herpes to new treatments for diabetes, their innovations could one day address some of the world’s most common health problems. This year’s two finalists in STAT Madness, a bracket-style competition showcasing cutting-edge research in the biomedical sciences, used new approaches to develop potential therapies that could help millions of people with all-too-common diseases.
A team from the Fred Hutchinson Cancer Research Center developed a gene editing technique with the potential to effectively treat and even cure herpes. The other finalist, a group from the Massachusetts Institute of Technology and Brigham and Women’s Hospital, developed a liquid solution that coats the small intestine with temporary adhesive, a non-invasive technique with wide uses from efficient drug delivery to the treatment of diabetes.
The competition was tough, with well over 1 million votes cast during the month-long competition that surpassed last year’s record of nearly 700,000 votes. In the end, both teams were declared winners. The STAT editors made this decision in the interests of fairness after discovering unusual voting patterns in the final round.
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Martine Aubert, Keith Jerome, and their colleagues at Fred Hutch tested a new method of gene therapy for treating herpes, improving earlier research by Jerome. Using gene editing in mice, the researchers removed over 90% of the virus from the cells it primarily infects, they reported in an article published in Nature.
Jerome, a virologist and professor at Fred Hutch University and the University of Washington, said that after years of improving his gene-editing approach, he was “more excited” than surprised by the promising results. “That’s what we wanted,” he said.
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Existing antiviral treatments for herpes usually treat the infection temporarily, but the latent virus still lingers in the body, hiding in the peripheral nerves, and responding regularly. Type 1 HSV usually causes cold sores around the mouth and lips; Type 2 causes sores on the genitals. Herpes is incredibly common, affecting more than two-thirds of people under the age of 50 worldwide. In their study, the researchers tested their treatment for the type 1 virus, but believe it would be effective for type 2 viruses as well.
In previous research, Aubert and Jerome had found that they could effectively target viral DNA in infected cells and damage the herpes virus using a DNA clipping enzyme called meganuclease. The enzymes used in the research were delivered to cells via a hollowed out virus-like particle called a viral vector. In the Nature study, the researchers also experimented with other gene editing approaches such as CRISPR / Cas9.
“You can see some signs [CRISPR/Cas9] worked a bit, but the meganucleases were much, much better, ”said Jerome.
Several incremental improvements to the researchers’ original method made it possible to destroy almost all of the herpes virus in the peripheral nerve cells of mice, while harming 4% or less of the virus in the first study.
In the new paper, the researchers hypothesized that if the technique worked in humans, it would decrease virus shedding, which would make it more difficult to pass the virus on to others. More recently, researchers have further supported this idea using a mouse model developed by Aubert that mimics virus shedding in humans. There has also been some evidence that the technique could be further improved so that herpes could be effectively cured.
“There could be a tweak in there [that would explain] why some animals do it better than others, ”said Aubert. For example, some mice had no detectable disease at all.
It can take at least two and a half years for treatment to kick into human studies, the researchers said. They plan to meet with the Food and Drug Administration by summer to discuss what safety data to collect before starting a clinical trial. The researchers also said the technique could potentially be used to treat hepatitis B and HIV.
Junwei Li led the winning team at MIT and Brigham and Women’s Hospital. Courtesy Melanie Gonick / MIT News
T.The other winning team was led by Junwei Li, a researcher at Brigham and Women’s Hospital and visiting scholar at MIT. The researchers developed a solution that reacts in the small intestine and covers it with a temporary adhesive. Giovanni Traverso, assistant professor of mechanical engineering at MIT and gastroenterologist at Brigham and Women’s Hospital, was the lead author of the study published in Science Translational Medicine.
Li said using the coating to deliver drug more efficiently was one of the researchers’ primary goals. Some drugs are quickly metabolized and mostly lost before the body absorbs all of the drugs, he said. The coating would slow the absorption of a drug, the researchers argued. The technology could make drugs not only more effective, but also cheaper, Li said.
“If we can increase that [absorption] For example, if you work five times, you can cut costs five times, ”he said.
The solution consists mainly of dopamine, which is a common neurotransmitter in the body. Once the dopamine gets into the small intestine, it reacts with an enzyme called catalase in the lining of the intestine. The reaction creates an adhesive polymer that temporarily coats the small intestine with a type of molecular glue. “The coating can stay there for 24 hours, which really maximizes the absorption window,” said Li.
Most of the nutrients and medicines are absorbed by the body in the small intestine and the highest concentration of catalase is also found. Because of this, the researchers found that the dopamine would not form a coating in areas they were not targeting, such as the stomach. They tested the method in the laboratory on human and pig tissue, as well as on live pigs, whose GI tracts are similar to those of humans. The solution was released into the pigs through a tube, but the researchers believe patients can drink or swallow it as a pill or capsule.
In a series of experiments, the researchers examined possible applications of the solution. In one case, they found that the drug praziquantel, which treats the tropical parasitic disease schistosomiasis, lasted much longer in pigs when combined with the solution. Praziquantel is usually taken three times a day, so using this technique may help reduce the frequency of dosing.
Li and his team also found that in pigs, the solution creates a more effective way of delivering the enzyme lactase to the digestive system, which could help lactose intolerant, and that the coating slows the rate at which glucose is absorbed, which could provide an alternative treatment for people with diabetes or obesity.
Safety tests of the solution in pigs and rats did not reveal any concerns.
The two teams triumphed from nearly 130 entries to the STAT competition, of which 64 entries were selected for the bracket. Contributions came from across the country and were selected on the basis of scientific accuracy, originality in their field and potential impact.
Jerome is grateful for the large community that supported his team’s research on social media, many of whom have herpes. He said he also enjoyed looking at all of the competitor’s research projects.
“I’ve learned a lot,” he said.
Li said he enjoyed engaging with his team’s research and learning about other teams’ studies. While some of the students in the lab were quite invested in the competition, Li said he was never particularly tied to winning. He sees the competition as being about exposing people to exciting new research and engaging with them. He also said the competition was a welcome distraction and a way to connect with fellow researchers at a time of social isolation.
“It was really fun, especially during the quarantine,” said Li.
