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

Thrasos治疗公司正在与卡尔加里大学的大卫·施里默教授合作， 涉及多发性骨髓瘤癌症患者肾衰竭治疗的分子机制。这 癌症在尿中产生高水平的抗体副产物，其与正常尿蛋白相互作用， 引起管型肾病的阻塞。管型肾病引起肾衰竭的发生率很高， 显著增加了多发性骨髓瘤相关的死亡率。这一现象在中国非常普遍， 在多发性骨髓瘤中，检测到这些阻塞证实了癌症的存在。的治疗 预期根除或预防阻塞可改善患者健康并提高总体存活率。 Thrasos有一种针对蛋白质相互作用的实验性疗法，可以减少 堵塞。然而，实验药物成功背后的分子特性尚不清楚。我们 试图确定形成堵塞的分子相互作用的性质，以及药物如何干扰 和他们将使用质谱技术进行蛋白质结构分析，以绘制 抗体副产物和宿主蛋白质之间结合域的化学性质和位置。 这些分析将扩展到药物/宿主-蛋白质相互作用，以确定 有助于其成功作为一个“重磅炸弹”。

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".