Padlock Therapeutics said today it has launched collaborations with investigators at NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and two research institutions specializing in protein-arginine deiminase (PAD) enzymes and their role in disease biology. The value of the collaboration was not disclosed.

The collaborations, according to Padlock, are designed to help the company create first-in-class treatments for autoimmune disease, building on past research on the inhibition of PAD enzymes and their role in initiating and perpetuating autoimmune diseases.

Padlock said its partnerships will be aimed at determining the role of individual PAD enzymes in certain animal disease models, and evaluating activity of its PAD inhibitors in enzymatic assays, animal models, and human cellular systems.

The collaborations will team up Padlock with:

  • Mariana Kaplan, M.D., chief of NIAMS’ Systemic Autoimmunity Branch, in studying the role of PADs and effect of proprietary inhibitors in neutrophil extracellular trap (NET) formation and animal models of systemic lupus erythematosus.
  • Kerri Mowen, Ph.D., of The Scripps Research Institute and one of Padlock’s scientific co-founders, in researching the role of PADs and effect of proprietary inhibitors in mouse models of rheumatoid arthritis.
  • Aaron Muth, Ph.D., of University of Massachusetts Medical School, in mechanism of action studies of proprietary PAD inhibitors. Dr. Muth is a principal investigator in the lab of Paul Thompson, Ph.D., a Padlock scientific founder and professor at UMass Medical School.

“These collaborators will help us expand our biology effort and advance our understanding of how best to target the PAD enzymes and maximize the potential our inhibitors may have for patients,” Michael Gilman, Ph.D., Padlock’s founder and CEO, said in a statement.

PADs are a family of enzymes that post-translationally modify amino acid side chains of arginine on proteins to the related amino acid citrulline. In some patients, these citrullinated proteins are immunogenic.

Padlock reasons that inhibiting PADs in these patients may provide an innovative, alternative approach to treating patients witih rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and other autoimmune diseases.