Liposomal Clondronate as a Treatment for Malignant Histiocytosis

02/01/2012

flat-coated retrieverMalignant histiocytosis (MH) is an extremely aggressive form of cancer that, while rare in general, is quite common in a number of dog breeds – including Bernese Mountain Dogs, Flat Coated Retrievers, Golden Retrievers, and Rottweilers. Dogs who develop this type of cancer, which causes tumors to form throughout the body, often die within only a few months of diagnosis, and it is very difficult to treat.

Because of its devastating effects on a number of highly loved dog breeds, the AKC Canine Health Foundation sponsors a great deal of research on the diagnosis and treatment of malignant histiocytosis. One such study, initiated by scientists at Colorado State University, has identified a potentially useful new therapeutic option – liposomal clondronate.

Liposomal clondronate is a drug made by incorporating the bisphosphonate clondronate into liposomes –small spheres made of a synthetic version of the lipid bilayers that surround animal cells. This form of clondronate is highly selective for the phagocytic cells that are the scavengers of the immune system, the cells from which MH originates.

Scientists had previously shown that liposomal clondronate was a safe and effective treatment for autoimmune hemolytic anemia in dogs. Since one of the ways it worked was to deplete the population of macrophages, which are one of the cell types that can mutate to become MH, researchers began to wonder if it might also be a useful therapeutic option for dogs with MH.  Their curiosity was also fueled by the fact that, for many years, liposomal clondronate has also been used to get rid of macrophages in mice.

Early evidence looks promising. When the Colorado scientists tested the drug in cell cultures derived from both MH tumors and non-MH tumors, they found that liposomal clondronate did a great job of specifically targeting the phagocytic MH tumor cells for killing. However, the effectiveness with which it killed MH tumor cells varied by tumor cell line, something that was not unexpected, since these cancers show significant variability from dog to dog.

That’s why, following those in vitro results, it wasn’t surprising that the effect of liposomal clodronate varied when the scientists attempted to treat five dogs with MH. What was surprising was how well the medication worked in two of the animals. It successfully caused the regression of tumors where previous treatments had failed – a very promising beginning.

Liposomal clondronate may not be the magic bullet that gets rid of malignant histiocytosis, but the study by Scott Hafeman and his colleagues clearly demonstrates that it’s a treatment worthy of more study. Even if the drug could only help a fraction of the dogs affected by MH, it would be a beacon of hope for the many dog owners who have lost beloved animals to this disease.

This work was funded by AKC Canine Health Foundation Grant 1472.

Scientific Publication:

Evaluation of liposomal clodronate for treatment of malignant histiocytosis in dogs. Scott Hafeman, Cheryl London, Robyn Elmslie and Steven Dow. Cancer Immunology, Immunotherapy. Volume 59, Number 3, 441-452, DOI: 10.1007/s00262-009-0763-y

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