J. Barnett, J. McCall, H. Blair, J. Soboloff, W. Geldenhuys
ExesaLibero Pharma, Inc,
Keywords: small molecule drug, space induced bone reduction, oral administration, osteoclast regulation
Summary:We are developing a drug that regulates the production of the cells that cause excessive bone loss associated with space travel. Normal bone health depends on new bone cell production by osteoblasts in complete balance with the removal of older bone by osteoclasts. When this balance is skewed so that more bone is removed than is produced, it causes a condition referred to as bone degrading disease or ‘bone erosion.’ Bone reduction associated with space travel is attributed to osteoclast activity exceeding bone cell production. Our drug, ELP-004, is a first-in-class small molecule drug with a novel mode of action; the control of osteoclast production. We have demonstrated that ELP-004 effectively controls bone loss in animal models of rheumatoid arthritis and multiple myeloma. ELP-004 shows very low toxicity and can control the development of the cells which cause bone erosion (osteoclasts); we hypothesize that ELP-004 will effectively reduce bone loss associated with space travel. We are currently performing a battery of tests to assess the preclinical toxicology of ELP-004. Data to date, which includes testing for genotoxicity, cardiotoxicity, hematotoxicity, and histopathology, show no toxicity issues at doses effective at reducing bone loss. These data will be used to obtain an Investigative New Drug (IND) designation from the FDA. Currently, DMARDs (disease-modifying anti-rheumatic drugs) are prescribed to control bone erosion; however, DMARDs act by inhibiting key components of the immune system, which renders the patient susceptible to infections and possible development of cancer. DMARDs require refrigeration and are administered by intramuscular injection, which makes them impractical to use during space flight. Bisphosphonates are another class of drug used to control bone loss; however, bisphosphonates also have an extensive list of side effects, such as gastrointestinal problems, preferential loss of bone in the lower jaw, and cardiotoxicity. Bisphosphonates are effective when administered intravenously; however, this is impractical for space travel. ELP-004 is stable at room temperature, is effective when taken orally, and does not have the side effects of currently available drugs, making it suitable for use during space travel.