Leukogene Therapeutics, a startup company from the Medical University of South Carolina (MUSC), has been awarded a $2 million Small Business Technology Transfer (STTR) grant to continue developing a new compound for treatment-resistant multiple myeloma.
The treatment prototype has shown promise in preclinical studies of treatment-resistant multiple myeloma and has the potential to be used with proteasome inhibitors.
Leukogene’s founder, Nathan G. Dolloff, PhD, and his research team are responsible for the development of the new therapy. Dolloff is an MUSC researcher, assistant professor in the Department of Cell and Molecular Pharmacology and Experimental Therapeutics at MUSC, and a member of MUSC Hollings Cancer Center.
This award funds the team’s work for two years, during which the team aims to improve the drug-like properties of the molecule, optimize its dose and treatment schedule in animal models, and start the pharmacology and toxicology experiments needed for filing an investigational new drug application with the U.S. Food and Drug Administration.
At the same time, they will also work on the product manufacturing and toxicology studies required by the FDA prior to the start of clinical trials.
To speed up the drug development process, Leukogene plans to look for industry partnerships.
“Our plan is, within the next six to twelve months, to find and develop the strongest possible drug candidate,” Dolloff said in a press release. “This will be the one that we hope to see in patients.”
Multiple myeloma is a type of cancer that affects plasma cells, which help fight off infection by producing lots of proteins called antibodies. Cancerous plasma cells make loads of useless and ineffective antibodies that need to be eliminated for cells to survive.
Proteasomes — tiny, barrel-shaped cellular structures — degrade misfolded, “used,” and nonfunctional proteins that have been molecularly tagged for destruction, acting as the cell’s protein garbage disposal.
Proteasome inhibitors are particularly useful for treating multiple myeloma because they stop the protein clearance process, leading to “bad” protein buildup, which causes the cell to blow up and die.
With recurrent use of proteasome inhibitors comes treatment resistance, but Dolloff’s team is working on a new therapeutic approach for treatment-resistant multiple myeloma patients.
“Nearly all myeloma patients eventually reach that stage when their physician tells them that they have explored all the options and that there’s nothing else,” Dolloff said. “Our goal has always been to develop that next treatment option and get it to patients as quickly as possible.”
Their work began six years ago with the development of lab-grown resistant myeloma cell lines. After screening more than 20,000 compounds, scientists found a molecule that reversed resistance to proteasome inhibitors in myeloma cells. In fact, the number of cancer cells in mice with myeloma were reduced after administration of this new compound, resulting in longer survival.
Dolloff’s molecule acts by preventing proper protein folding, which is key to protein function. By administering the new compound with a proteasome inhibitor, researchers believe they are delivering a one-two punch to cancer cells.
“We’re creating a lot of misfolded junk proteins, and that, in and of itself, is toxic to myeloma cells,” Dolloff said. “But because we are also blocking the breakdown side with proteasome inhibitors, we have a two-hit strategy that is extremely effective at killing myeloma cells.”
Additionally, according to the press release, the team’s preliminary research suggests that this new molecule is also effective in other cancer types and boosts other cancer therapies besides proteasome inhibitors.
“One of the exciting things is that we think this goes well beyond myeloma and we can apply this to a lot of different cancers,” Dolloff said. “We may even be able to enhance a few drugs other than proteasome inhibitors.”