Office of Technology Transfer – University of Michigan

CARD-024 Amelioration of Intestinal Fibrosis and Use for Treatment of Crohn's Disease

Technology #5383

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Researchers
Peter D. Higgins
Robert U. Simpson
Managed By
Robin Rasor
Managing Director of Licensing (734) 615-8433
Patent Protection

US Patent Pending

Crohn’s disease is a chronic inflammatory bowel disease in which there are periods of inflammation of the gastrointestinal lining followed by periods of mucosal healing. There is no cure for Chron’s and it affects roughly 200 out of every 100,000 adults. Though Chron’s can be managed with anti-inflammatory therapies and immune system suppressors, nearly 70% of patients develop excessive scar tissue buildup that leads to bowel obstruction known as fibrostenotic disease. There are currently no effective drug therapies for fibroses and it often requires surgery to remove the scar tissue, emphasizing the need for a treatment of fibrosis. . Another side-affect of Crohn’s disease is vitamin D deficiency, which has been linked to fibrosis in other organ systems. This technology investigated a vitamin D analog, CARD-024, and demonstrated that it is able to attenuate colonic myofibrils and possibly help in the treatment of intestinal fibrosis.

CARD-024 amelioration of intestinal fibrosis and use for treatment of Crohn’s disease

Vitamin D analogs have been used to reduce kidney, cardiac, and renal fibrosis in certain animal models and have been used as therapies for several diseases but they often produce high levels of calcium in the blood that can be toxic. This technology demonstrates that vitamin D analog CARD-024 reduces intestinal myofibrils when TGFβ or a physiologically stiff matrix stimulates the development of myofibrils. In these studies, treatment of induced myofibrils with CARD-024 caused a repression of αSMA, a hallmark protein of myofibroblasts, repression of stiffness induced morphological changes, as well as repression of FAK phosphorylation, which mediates myofribroblast differentiation. Additionally, CARD-024 is a non-hypercalcemic molecule and therefore will not produce the high calcium levels that have been seen when using other vitamin D analogs. These findings suggest that CARD-024 could be used as a therapy to treat the symptoms of Crohn’s disease by reducing intestinal fibrosis.

Applications

  • New drug compound
  • Treatment of intestinal fibrosis
  • Possible treatment of other types of fibrosis
  • Therapy for management of Chron’s Disease
  • Therapy for other inflammatory bowel diseases

Advantages

  • No current therapies
  • Reduce amount of surgeries
  • Low hypercalcemic affects