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Targeting the SLIT3 Pathway to Promote Bone Formation
Weill Cornell Medicine
Protein
Musculoskeletal disease, Endocrinology
Hit To Lead or Lead Optimization
Background
• One in two women and one in four men experience a fracture due to osteoporosis in their lifetime. However, the application of currently available therapeutic methods is limited by either the side
effects or by the maximum therapy duration
• Biophosphonates are the most widely prescribed but are associated with nausea, abdominal pain and heartburn-like symptoms
• Denosumab produces similar or better bone density results but is associated with rare but serious side effects
• Bone-building medications such as teriparatide and romosozumab may be used in patients who fail or are intolerant to other therapies
Unmet Needs
Methods to prevent and reverse osteoporosis that act through novel mechanisms
Technology Overview
• Novel methods that involves targeted administration of osteoanabolic agents to promote bone formation, boost bone strength, and enhance bone healing
• Slit guidance ligand 3 (SLIT3) is a potent proangiogenic factor that enhances bone fracture healing and counteracts bone loss
• In a mouse model of osteoporosis, SLIT3 had comparable efficacy to PTH-based anabolic agents
• Local therapeutic delivery was achieved using a SLIT3-loaded collagen sponge, which limits potential for extra-skeletal toxicities
• SLIT3 provides a complementary pathway to PTH-based agents, suggesting they may be used sequentially or in combination to enhance efficacy
Matthew Greenblatt, Laurie Glimcher
PCT-US2019-018115 (2019.02.14)
Patent Family: PCT, US
"Senolytics improve physical function and increase lifespan in old age". Xu, M. et al. Nature Medicine 2018, 24(8), 1246–1256
