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New Connecticut company developing treatment for most aggressive brain tumors
Hartford Courant - 7/30/2022
A new treatment for glioblastoma and similar cancers targets the tumor cells’ DNA so that they can’t divide while leaving healthy tissue undisturbed, according to research published by Yale University researchers.
The same day, Dr. Ranjit Bindra, Seth Herzon and their co-founders announced the launch of their startup, Modifi Biosciences, which they hope will turn their research into a viable drug within 1 1/2 years.
Their paper was published in the journal Science.
“At a high level, this scientific paper is really defining a new way to exploit cancer cells or tumors that have defects in DNA repair,” said Bindra, professor of therapeutic radiology at Yale School of Medicine and scientific director of the Chênevert Family Brain Tumor Center at Smilow Cancer Hospital in New Haven. He also is CEO of Modifi Biosciences.
Their treatment can be used in gliomas and other cancers that have defects in the ability to repair DNA. “Subsets of colon cancer, lung cancer, sarcoma are examples of tumors [in which] these molecules could show promising activity,” Bindra said.
“We’ve shown a new way to modify the DNA itself in a manner that tumor cells that have these defects in DNA repair would be killed while the normal tissue would survive,” he said.
So far, the technique has shown promise in animal studies, so the group is hoping to advance its research at “light speed,” Bindra said. “In the next year and a half, the company is going to take the discovery in Science and turn it into a drug molecule chemically distinct from what we’ve had before,” Bindra said.
The drug now used to treat glioblastoma, temozolomide, works by preventing cancer cells from reproducing DNA. It has been the standard treatment for 20 years, Bindra said. But cancer cells develop resistance to the drug. The five-year survival rate for glioblastoma is just 6.8 percent, and the average length of survival is eight months, according to the National Brain Tumor Society. Glioblastomas account for half of all brain tumors.
“What we’ve done in the paper that’s appearing in Science is we’ve been able to … design molecules so they only destroy the tumor cells,” said Herzon, a chemistry professor at Yale. He called that ability the “Holy Grail” that scientists have sought since the 1940s.
“The compounds generate a … type of toxic modification” to the tumor cells’ DNA, Herzon said. “They essentially stitch the two strands of DNA together in a way that can’t be resolved. We’ve essentially stapled them together.”
DNA, situated in almost every cell in the body, carries the genetic material that makes each person unique. It is shaped as a double helix, almost like a spiral staircase with the genes forming the steps.
In cancers like glioblastoma, the DNA has difficulty repairing itself, which is what the researchers targeted. By linking the two strands in a way that the cancer DNA cannot repair itself, the cell dies. “At that point, it’s game over,” Herzon said.
Healthy cells, however, are able to undo the cross-link, he said.
“We demonstrate that we’re able to increase the lifespan of mice essentially for as long as we run the experiment,” Herzon said.
Bindra said one advantage to their new drug is that “a lot of patients get conventional therapies that have some similarities to the drugs that we’re making.”
“Even if they’ve acquired mutations that have been known to become resistant, the molecules are designed in such a way that those resistant mutations will not affect the activity of our molecules,” he said.
Bindra said the new company, which has licensed exclusive rights to the research from Yale, came out of “stealth mode” at the same time the paper was published. It is based in the new Elm City Bioscience Center at 55 Church St. in New Haven.
According to the National Brain Tumor Society, there are 20,000 glioma cases diagnosed each year in the United States, and more than half are glioblastomas.
Ed Stannard can be reached at email@example.com, 203-993-8109.
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