Technical Field:

Therapeutic: Arthritis and Inflammation

The Problem: 

Matrix metalloproteinases (MMPs) are enzymes that cause tissue destruction in chronic diseases such as arthritis, degenerative disc disease, and skin ulcers. Primary MMP inhibitors have not been clinically successful.

The Technology Solution:

Using their knowledge of the molecular pathways that lead to MMP expression and activation, researchers at the University of Tennessee have targeted IL-1 mediated signaling to control MMP activity. Specifically the inventors have demonstrated that levels of icIL-1ra (Intracellular IL-1 Receptor Antagonist) confer resistance to pro-inflammatory signals and prevent increased MMP expression. The inventors have further identified several small peptides (5 to 42 amino acids), fragments of icIL-1ra, which are capable of inhibiting tissue destruction. Intriguingly, these peptides were shown to be acting through a mechanism independent of the IL-1 cell surface receptor.

The researchers have tested their peptides in both cell culture and animal models. In vitro the peptides were shown to be anti-proliferative and to reduce MMP production. In the mouse collagen-induced arthritis model the peptides were shown to suppress arthritis, as measured by the severity of inflammation and swelling in the paw.

Related Publication:

• Journal of Investigative Dermatology (2006) 126, 756–765

Applications:

Treatment for arthritis, degenerative disc disease, chronic skin ulcers

Patents:

• Two issued US patents (7,482,323 and 7,674,464)

Benefits: 

• New mechanism for MMP inhibition

• Issued US patents

• Subcutaneous administration was effective in mouse model of arthritis

The Inventors:

Dr. Karen Hasty is the George Thomas Wilhelm Endowed Professor of Orthopaedic Surgery, in the Department of Orthopaedic Surgery/Campbell Clinic at UTHSC. She is also a Research Career Scientist with a VA Merit Review Award at the VA Medical Center in Memphis. She serves as a member of the Board of Trustees of the Campbell Foundation. Dr. Hasty has served as principal investigator on numerous projects funded by NIH, VA and the Arthritis Foundation spanning a 25-year career in arthritis and orthopaedic research with published 75 research papers.

Dr. Arnold Postlethwaite is the Goodman Chair of Excellence Professor in Medicine and the Director of the Division of Connective Tissue Diseases (Rheumatology) at University of Tennessee Health Science Center. He has extensive research experience in the fields of autoimmune diseases, connective tissue, arthritis, and fibrosis including having designed and led several investigator-initiated clinical trials. He is also a consultant to Argentis Pharmaceuticals, a biotech startup in Memphis that is developing a treatment he discovered for scleroderma.

Reference: PD 03044