(Press-News.org) JUPITER, Fla. — A potential treatment for glioblastoma crafted by scientists at The Wertheim UF Scripps Institute renders the deadly brain cancer newly sensitive to both radiation and chemotherapy drugs, and blocks the cancer’s ability to invade other tissue, a new study shows.
The experimental medication, called MT-125, has received approval from the FDA to move to clinical trials as a possible first-line treatment for the most aggressive form of the brain cancer.
Each year, 14,000 people in the United States receive the devastating news that they have glioblastoma. It is a cancer with an average survival of just 14 to 16 months. Standard treatments include surgery, radiation and chemotherapy. But half of glioblastoma patients have a subtype that doesn’t respond to any approved cancer drugs, said Courtney Miller, Ph.D., a professor and academic affairs director at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology.
New options are urgently needed for those patients, said Miller, a member of the University of Florida Health Cancer Center.
“We know glioblastoma patients are awaiting a breakthrough, and we are moving as fast as humanly possible,” she said.
Miller and her colleagues have long focused on molecular “motors” in the cell, nanoscale proteins called myosin. They look and act like machines, converting the cell’s energy into activity. Myosin motors enable cells to move, connect to other cells or contract and expand, Miller said. They are found throughout the body, including in heart, muscle and brain tissue.
As a result, they have potential as therapeutic targets for a wide range of conditions, from cancer to substance use disorders, she said. However, there are no current medications that target them, or even selective drug-like tools that scientists can use to study them.
Miller teamed up with her Wertheim UF Scripps colleagues to design a spectrum of potential drug candidates to block myosin motors in different contexts. Their work was published Tuesday, July 1, in the scientific journal Cell.
Medicinal chemist Theodore Kamenecka, Ph.D., engineered the array of compounds, in consultation with structural biologist Patrick Griffin, Ph.D., The Wertheim UF Scripps Institute’s scientific director.
To test the oncology potential of the myosin motor drugs, the team joined forces with Steven Rosenfeld, M.D., Ph.D., a scientist and neuro-oncologist at the Mayo Clinic in Jacksonville. Their out-of-the-box strategy appears to have opened a new route to attacking the hardest-to-treat glioblastoma. It works in four ways, the scientists reported in a companion paper published in Cell on June 10.
“In animal studies, MT-125 makes malignant cells that were previously resistant to radiation responsive to it,” Miller said. “You also end up with multinucleated cells that cannot separate, and so they get marked for cell death.”
MT-125 also blocks the cells’ ability to squeeze and change shape, which means they cannot proliferate and invade other parts of the brain, she said. And if MT-125 is combined with existing chemotherapy drugs, including sunitinib, the drug appears to deliver a very powerful response, Rosenfeld said. Sunitinib belongs to a class of chemotherapy drugs called kinase inhibitors.
“We found in mice that combining MT-125 with a number of kinase inhibitors created long periods of a disease-free state that we haven’t seen in these mouse models before,” Rosenfeld said.
The scientists cautioned that many potential drugs that perform well in mice fail in human studies, due to differences in biology, so it will take time and study to learn if MT-125 is the hoped-for breakthrough, Rosenfeld said.
Toxicity is another worry. But because the cancer cells are much more sensitive to MT-125 than healthy cells, and because the drug doesn’t stay in the body long, pulsed administration of the medication over a brief period seems to address the issue, Rosenfeld said.
“I have been in the field for 35 years, and I always thought the solution to this problem would have to come from out-of-the-box thinking,” Rosenfeld said. “The tried-and-true methods don’t seem to work for this disease.”
The compound, MT-125, has been licensed to a Jupiter, Florida-based biotechnology company started by the scientists, Myosin Therapeutics. They are working hard to begin first-in-human clinical trials within the year in glioblastoma patients, Miller said. The U.S. Food and Drug Administration has given them the green light to proceed. They are awaiting release of a federal grant that has internal approval, she said. The National Institutes of Health has provided study funding, as well as the William Potter Glioblastoma Research Fund at The Wertheim UF Scripps Institute, which was established by William Potter’s wife, Ronnie Potter, in his memory.
Looking ahead, Miller says there is evidence that MT-125 could prove beneficial not only against the aggressive variant of glioblastoma, but for malignant gliomas and other cancers.
In parallel, Miller and her collaborators are working to prepare a clinical trial for a related compound, MT-110, which appears to block drug cravings for people with methamphetamine use disorder. This compound is described in more detail in the July 1 Cell study.
END
Scientists wipe out aggressive brain cancer tumors by targeting cellular ‘motors’
In animal studies, MT-125 makes malignant cells that were previously resistant to radiation responsive to it, and thwarts cancer in three other ways.
2025-07-01
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[Press-News.org] Scientists wipe out aggressive brain cancer tumors by targeting cellular ‘motors’In animal studies, MT-125 makes malignant cells that were previously resistant to radiation responsive to it, and thwarts cancer in three other ways.