Novel Compound Shows Promise In Fighting Multiple Myeloma
By C. Rajan, contributing writer
Scientists at the Dana-Farber Cancer Institute have shown that a novel compound prevents metastasis of multiple myeloma in mouse models, and it is this discovery that will form the basis of the company’s future plans to progress the compound into human trials.
Cancer metastasis, the spreading of tumors to distant parts of the body, is one of the most deadly features of cancer. In particular, multiple myeloma, a blood cancer that originates in the bone marrow, is highly metastatic in nature and spreads to the bones to form multiple tumors. The American Cancer Society estimates that there will be approximately 11,090 deaths in 2014 due to multiple myeloma.
The lead investigator of the study, Dr. Irene Ghobrial, at Dana-Farber's Center for Hematologic Oncology, says, "Metastasis remains one of the most formidable complications we face as cancer researchers and physicians. Improvements in the treatment of metastatic cancers have, for the most part, not been nearly as dramatic as in primary disease."
In an attempt to fight the process of metastasis, Ghobrial and her team zoned in on a substance called stromal cell-derived factor-1 (SDF-1), which is responsible for attracting certain cells to new locations within the bone marrow. They found elevated levels of SDF-1 at the sites in where metastasis had occurred in mice with advanced stages of melanoma.
Ghobrial and her team hypothesized that blocking SDF-1 with a chemical substance could make the bone marrow environment less receptive for multiple myeloma cells, and therefore keep the disease from progressing.
The researchers collaborated with NOXXON Pharma, a German biotech company, to test a compound, olaptesed pegol, that binds tightly and specifically to SDF-1.
Laboratory experiments by Ghobrial’s team showed that olaptesed pegol blocks the activity of SDF-1, thus lowering its affinity for the tumor cells. In mice, the researchers found that olaptesed pegol altered the bone marrow and made it unreceptive to myeloma cells. As a result, the disease progressed more slowly, and the animal survived longer.
The blood-borne myeloma cells that are prevented from metastasizing to the bones don’t appear to form new tumors in other locations. "We know that myeloma cells can't survive for long if they're circulating in the blood and can't adhere to other tissue," Ghobrial remarked. "We saw no evidence that they had metastasized and begun to grow in other tissue, either.
"Our findings clearly document a therapeutic effect of olaptesed pegol in a mouse model of advanced myeloma," Ghobrial continued. "It is now being tested in a clinical trial of multiple myeloma patients, with more trials to come."
Olaptesed pegol, a PEGylated mirror-image L-oligonucleotide, is being developed by NOXXON for hematological cancers, including multiple myeloma and chronic lymphocytic leukemia (CLL). It is currently being tested in Phase 2a studies for multiple myeloma and CLL. The novel compound has also recently received Orphan Drug Designation from the FDA for treatment of glioblastoma.
The study is published in the Sept. 25 issue of the journal Cell Reports.