Pentosan polysulfate (PPS), an approved medicine, may be a potential add-on treatment for Gaucher disease, helping reduce inflammation and bone alterations in cellular models of the condition, a study found.
The treatment was also effective in cell models of Fabry disease, another lysosomal storage disorder.
The study, “Efficacy of pentosan polysulfate in in vitro models of lysosomal storage disorders: Fabry and Gaucher Disease,” was published in the journal PLOS ONE.
Both Fabry and Gaucher diseases are lysosomal storage disorders characterized by the buildup of a specific fat molecule (lipid). The diseases are caused by mutations in the enzymes that degrade those lipids, and are often treated with disease-modifying treatments, such as enzyme replacement therapy. However, patients rarely see a restoration of their complete health status, meaning that additional treatments are needed.
Inflammation is a hallmark of these diseases; researchers think that directly reducing that inflammation may be helpful in some patients.
PPS is a mixture of semisynthetic sulfated polyanions (which are, essentially, complex salts including sulfur atoms). Approved as Elmiron for the treatment of pain in internal cystitis, PPS has been shown to have anti-inflammatory properties, although its precise mechanism of action remains obscure. Might PPS be a viable anti-inflammatory treatment for Gaucher and Fabry disease?
To find out, researchers isolated immune cells from the blood of people with both diseases, as well as controls without either disease. They then treated these cells with PPS and measured the levels of pro-inflammatory molecules that the cells produced.
In both disease types, PPS treatment reduced the secretion of IL-1β, TNFα and IL-4, all of which help drive inflammation. Some other inflammatory molecules (specifically IL-6 and IL-10) were reduced by PPS in Fabry disease immune cells, but not in Gaucher disease cells.
Also, PPS did not change levels of chitotriosidase — a marker of disease activity — in Gaucher disease immune cells, nor did it affect lipid storage in the cells.
Importantly, production of all the aforementioned molecules was not significantly changed by PPS when control cells (cells from people without Gaucher or Fabry) were treated.
The researchers also took supernatant (the liquid the cells live in, in a dish) from PPS-treated or untreated immune cells and used it to treat bone cells, as skeletal problems are a major issue in these diseases.
They found that supernatant from untreated cells induced changes in the bone cells, and these changes were lessened in cells treated with supernatant from PPS-treated immune cells. The changes in bone cells are associated with bone resorption, which would, by extension, translate to bone loss in a body.
In simplest terms, the data suggest that PPS treatment causes immune cells to produce fewer pro-inflammatory molecules and fewer bone-damaging signals.
“These results serve as preclinical supportive data to start clinical trials in human patients to analyze the effect of PPS as a potential adjunctive therapy for Fabry and Gaucher diseases,” the researchers stated.
It is worth emphasizing that these results are from cells in dishes; more work will be needed to determine whether PPS is truly a viable treatment for Gaucher and Fabry diseases. It also should be noted that some of the researchers disclosed financial interests (i.e. patents) in PPS.