Multiple myeloma (MM) is the second most common hematological malignancy. Even though significant improvements have been made last decades, it remains an incurable disease. MM is a B cell cancer mainly characterized by the proliferation of malignant plasma cells in the bone marrow, the presence of monoclonal serum immunoglobulin, and the occurrence of osteolytic lesions. MM is highly associated with bone destruction. Osteoclasts (OCs) were shown to enhance bone destruction and support myeloma progression, while osteoblasts (OBs) enhanced bone formation and inhibited myeloma growth. In MM, the activities of OCs were up-regulated, while the OB activity was down-regulated. This evidence suggested that manipulating activities of OCs and/or OBs can be a good candidate for novel myeloma therapy.

Wounds are a major global challenge and pose a significant risk in public healthcare. It impacts over 50 million individuals in the United States annually, and the costs exceed $20 billion. Furthermore, extrinsic injury-induced trauma and scar formation may elicit complex health problems. In a healthy condition, a highly efficient innate host defense system continually monitors and heals wounds in an orderly and timely manner; various intracellular and intercellular pathways are activated and coordinated, thus restoring tissue integrity and homeostasis. However, combining the prevalence of diabetes, obesity, aging, neuropathy, or repeated mechanical stress may cause wounds to remain unresolvable for several months, resulting in chronic wounds. Furthermore, the wound healing process often results in scar formation from disorganized fibroblasts and collagen, leading to sociological and psychological trauma in patients. After cutaneous injury, a wound undergoes different processes; hemostasis, inflammation, proliferation, and maturation. Calcium regulates inflammatory cell infiltration, fibroblast proliferation, and keratinocyte migration.

Sigma Anti-Bonding Molecule Calcium Carbonate (SAC) is a chemically modified calcium carbonate with a unique weak bonding structure that significantly increases the calcium absorbing rate in our body. It can influence environmental calcium levels and modulate calcium homeostasis in vivo. Calcium plays an important role in bone homeostasis and wound healing. We hypothesized that SAC might provide positive effects on these phenomena.

During Phase I, we explored various potential roles of SAC in normo- and pathophysiology and tested various routes of SAC administration (such as topical cream, intravenous/intraperitoneal injection, and gavage) in a mouse for maximal physiological effect. In these trials, we found that i) SAC facilitates skin wound healing and ii) SAC delays multiple myeloma progression via gavage and intraperitoneal injection.
Based on these findings, we propose to pursue the following aims during Phase II;
i) We will test whether the SAC delays the Mouse MM progression and investigate a mechanism of this anti-MM action via bone formation and/or gut microbiota symbiosis.
ii) We will test the SAC effect(s) on mouse wound healing and investigate the mechanism of this action.
iii) We will continue to explore the pharmacological effects of SAC on various conditions.

We anticipate submitting two manuscripts in the next six months based on current findings. We will continue to pursue the proposed studies and publish more as we obtain new results. For Aim iii, we will expand our study to other normo- and pathophysiology fields through various collaborations with other investigators within and outside the institution.

CBHI CRAC23992

2023-06-21

2028-06-20