2018-388 METABOLIC REQUIREMENTS FOR ALTERNATIVE MACROPHAGE ACTIVATION

Metabolic Requirements for Alternative Macrophage Activation

SUMMARY

UCLA researchers in the Department of Molecular and Medical Pharmacology have discovered that Coenzyme A is a targetable requirement for anti-inflammatory macrophage differentiation.

BACKGROUND

A dysregulated immune response is a hallmark of many disease phenotypes. For instance, cancer cells can reprogram healthy cells of the innate immune cells to work in conjunction to promote cancer cell growth. There are currently a number of methods being explored to combat this reprogramming, though these methods have shown limited success. There exists an unmet need for a therapy that relies on naturally-occurring bodily substances to help combat this reprogramming either on its own or in conjunction with current standard-of-care cancer treatments such as chemotherapy.

INNOVATION

Drs. Divakaruni and Bensinger at UCLA have discovered that Coenzyme-A (CoA) is a targetable requirement for anti-inflammatory macrophage differentiation. This discovery provides a potential point of targeting for macrophage differentiation in cancer models. The identification of CoA as a target for macrophage differentiation can also be used as a point of therapy for many other diseases where an excessive anti-inflammatory response can be causative of pathology (e.g. fibrotic disease, NASH/NAFLD, etc.).

APPLICATIONS

• Elevate CoA levels to improve conditions involving excess inflammation, in cases like: parasitic infections, diet induced obesity, sepsis, rheumatoid arthritis, eczemas, allergic or atopic dermatitis, and inflammatory conditions of the eye
• Topical, subcutaneous, or intravenous application of CoA could also lead to benefits for: wound healing following surgeries, injuries, burn, or skin damage due to radiation or sunburn 
• Lowering levels of CoA could help to treat: non-alcoholic fatty liver disease and hepatic steatosis, pulmonary fibrosis, cardiac hypertrophy, and certain cancers.

ADVANTAGES

• First study to show that CoA is a targetable requirement for anti-inflammatory macrophage differentiation
• Study directly suggests that drugs that could target rate-controlling enzymes in CoA biosynthesis could help to treat diseases like: fatty liver disease, non-alcoholic hepatic steatosis, pulmonary fibrosis, cardiac hypertrophy, and cancer (targets not typically used currently)
• The suggested use of increasing CoA could be strong evidence for why pre-existing supplements are good for one’s health

RELATED MATERIALS

A. S. Divakaruni, W. Y. Hsieh, L. Minarrieta, T. N. Duong, K. K. O. Kim, B. R. Desousa, A. Y. Andreyev, C. E. Bowman, K. Caradonna, B. P. Dranka, D. A. Ferrick, M. Liesa, L. Stile, G. W. Rogers, D. Braas, T. P. Ciaraldi, M. J. Wolfgang, T. Sparwasser, L. Berod, S. J. Bensinger, A. N. Murphy, Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostatis, Cell Metabolism, 2018.