Primary myelofibrosis (PMF), a relatively rare but painful type of bone marrow cancer, disrupts the body’s production of blood cells by causing extensive scars in the bone marrow. Unfortunately, few treatment options are available, most of which are palliative. The only curative treatment is a stem cell transplant, for which few patients are eligible.
A new study by researchers at Boston University School of Medicine (BUSM), led by author Katya Ravid, DSc, found that the drugs PXS-LOX_1 and PXS-LOX_2 can slow the progression of PMF disease in experimental models.
According to Ravid, professor of medicine and biochemistry at BUSM and professor of biology at Boston University, these drugs are unique in that they can block their target, a protein called lysyl oxidase, with a combination of specificity and effectiveness that has not been previously tested Drugs. These current results build on previous discoveries and publications by Ravid and her group and show which specific proteins in bone marrow cause the scarring effect seen in PMF.
Three experimental models were used for this study: the first group was normal, while the other two had genetic changes that caused them to develop cancer in the bone marrow. The drug PXS-LOX_1 was given to all three groups. While it did not cause significant changes in the normal models, it reduced the severity of bone marrow cancer symptoms in both modified groups. In a separate experiment, PXS-LOX_2 was administered to the normal set and one of the genetically modified groups. This test did not reveal any change in the normal group, but rather a decrease in the severity of cancer symptoms in the modified models.
Ravid believes these results are important because they represent a potential new treatment pathway for PMF as there are currently no drugs available that target diseased bone marrow matrix proteins in the way that PXS-LOX_1 and PXS-LOX_2 do. “If at some point these drugs are approved for human use, they could help slow the progression of cancer and alleviate the painful symptoms of the disease.”
The researchers hope that this study will help develop novel treatments for primary myelofibrosis. Based on this study, the Australian Biotech Pharmaxis has initiated phase 1-2 clinical trials in humans.
These results appear online in the journal Archives of Stem Cell and Therapy.
Boston University School of Medicine
A. Piasecki et al. (2020) Lysyl oxidase Inhibition in Primary Myelofibrosis: A Renewed Strategy. Archive for stem cells and therapy. doi.org/10.46439/stemcell.1.005.