Role of Immunoglobulin Light Chain Derived Peptides in Preventing Multiple Myeloma Associated Cast Nephropathy

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Thrasos Therapeutics Inc. is collaborating with Prof. David Schriemer (University of Calgary) to understand molecular mechanisms involving a treatment of renal failure in cancer patients with multiple myeloma. This cancer generates high levels of antibody byproducts in the urine, which interact with normal urine protein and cause blockages called cast nephropathies. The incidence of renal failure from cast nephropathies is high, and significantly adds to the mortality rate associated with multiple myeloma. The phenomenon is so common in multiple myeloma that detection of these blockages confirms the presence of the cancer. Treatments that eradicate or prevent the blockages are anticipated to improve patient health and improve overall survival rates. Thrasos has an experimental therapy targeting the protein interaction, shown to reduce the formation of blockages. However, the molecular properties behind the success of the experimental drug are unknown. We seek to determine the nature of the molecular interactions that form the blockages, and how the drug interferes with them. Protein structural analyses will be performed using mass spectrometric techniques, in order to map the chemical nature and location of the binding domains between the antibody byproducts and the host protein. These analyses will be extended to the drug/host-protein interaction, to identify the molecular features that contribute to its success as a "blockage-buster".