Novel materials show promise in treating multiple myeloma bone lesions

The team tackled a critical challenge in treating multiple myeloma-a blood cancer where malignant plasma cells accumulate in bone marrow, leading to debilitating bone lesions in 80% of patients. These lesions cause severe pain and fractures that often fail to heal, and within, a vicious cycle takes place that supports tumor survival and regrowth.

Through our multidisciplinary effort, we aimed to develop advanced bone repair materials capable of mimicking the stability of healthy trabecular bone while promoting bone healing by reducing the activity of bone-resorbing cells (osteoclasts) and enhancing bone-building cell (osteoblast) function, and which at the same time can deliver localized drug treatments to suppress tumor activity and support bone regeneration."

Professor Dirk Hose of TORC

The result of their efforts is "sicXer," a so called "mesoporous silica-collagen xerogel" engineered to closely resemble mineralized collagen, the structural foundation of bone. Leveraging innovative silica-based mineralization inspired by marine glass sponge spicules, the team tailored the mechanical properties and degradation kinetics of sicXer to closely match human bone.

"Building on sicXer, we developed "boXer," a drug-loaded version of the material. BoXer incorporates the anti-myeloma drug bortezomib, an agent known to stimulate net bone formation while effectively killing tumor cells. BoXer releases this "payload" locally at the site of bone lesions, offering a dual therapeutic benefit-bone regeneration and localized myeloma control." Dr. Anja Seckinger of TORC adds.

In their forthcoming paper, the researchers demonstrate boXer's ability to stimulate bone formation in preclinical models of healthy and diseased bone. They also managed to suppress myeloma cells, including those resistant to systemic bortezomib treatment. The results show promising potential for stabilization and healing of fracture-prone bone lesions.

The research team envisions sicXer and boXer as components of a novel combined systemic and local treatment strategy for multiple myeloma. Beyond oncology, these materials may have applications in non-malignant diseases involving bone degeneration or fractures.

"This innovation addresses a significant unmet need in multiple myeloma treatment by combining structural bone repair with targeted tumor control. We are eager to move towards clinical testing to realize the potential of sicXer and boXer in improving patient outcomes." Professor Hose concludes.

Source:
Journal reference:

Hose, D., et al. (2024) Bortezomib-releasing silica-collagen xerogels for local treatment of osteolytic bone- and minimal residual disease in multiple myeloma. J Hematol Oncoldoi.org/10.1186/s13045-024-01636-4.

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