BACKGROUND:  Inhibiting immune responses is important both in transplant medicine and in the treatment of autoimmune and inflammatory diseases. The immunosuppressive drugs currently used as treatments are cyclosporine A, tacrolimus, and their derivatives. These drugs display multiple toxic side effects including nephrotoxicity, neurotoxicity, and GI disturbances. As a result, these drugs have limited therapeutic usefulness for transplant patients and patients with autoimmune diseases.

The CRAC channel has been shown to be a critical component for generation of a productive immune response. Currently marketed drugs acting on the CRAC channel function through regulation of targets downstream of CRAC and suffer from a range of undesirable side effects. Since the strict predominance of CRAC is found only in immune cells, therapies that target the CRAC channel itself are promising options for the inhibition of immune responses while also limiting side effects.

INNOVATION:  Researchers at UCLA have identified a novel peptide that specifically blocks CRAC channel activity. The peptide functions by inhibiting the gene responsible for encoding the CRAC channel. The peptide treatment represents the first identification of an inactivation mechanism for the gene. As a result, the peptide can block CRAC currents specifically in immune cells.

POTENTIAL APPLICATIONS 

• Treatment of autoimmune or inflammatory diseases, including multiple sclerosis, rheumatoid arthritis, asthma, and inflammatory bowel disease
• Prevention of transplant rejection during organ replacement surgery

ADVANTAGES

• The peptide blocks CRAC currents specifically in immune cells, reducing side effects vs. current treatments
• The peptide treatment is derived from an endogenous peptide, and thus may avoid immune responses against the peptide itself

DEVELOPMENT-TO-DATE:  The success of the peptide in blocking CRAC channel activity has been demonstrated in cell lines and primary murine T cells. The current peptide is 37 amino acids and investigators are currently identifying a core sequence effective for inhibiting the CRAC channel function.

Reference: UCLA Case No. 2009-593