Hebrew University researcher develops anti-inflammatory and anti-allergic family of drugs

Hebrew University of JerusalemSep 7 2012

A synthetic, anti-inflammatory and anti-allergic family of drugs to combat a variety of illnesses while avoiding detrimental side effects has been developed by a Hebrew University of Jerusalem researcher.

The researcher is Saul Yedgar, who is the Walter and Greta Stiel Professor of Heart Studies at the Institute for Medical Research Israel-Canada at the Hebrew University Faculty of Medicine.

Inflammatory/allergic diseases affect billions of people worldwide, and treatments for these conditions are a major focus of the pharmaceutical industry. The most common drugs currently used to treat these numerous diseases are steroids, which are potent but are associated with severe side effects. These include metabolic changes (weight gain, increased blood pressure, diabetes), organ-specific effects (glaucoma, cataracts, bone fragility), and even psychotrophic side effects (depression, psychosis).

For decades, alternatives, such as biological NSAIDs (non-steroidal alternative anti-inflammatory drugs) have been the focus of the pharmaceutical industry. The resulting drugs have been commercially successful, but have not produced genuine alternatives to steroids due to their limitations. Synthetic NSAIDs are less potent and have their own serious side effects, including cardiovascular disorders, stomach bleeding and respiratory disorders. The biological drugs are costly and, must be injected and have rare but very severe side effects.

Inflammatory/allergic diseases present different symptoms affecting different organs, such as skin inflammations (dermatitis, psoriasis); airway injury and allergy (asthma, cystic fibrosis, allergic rhinitis); osteoarthritis and rheumatoid arthritis; intestinal inflammation (ulcerative colitis, Crohn's disease); central nervous system inflammation (multiple sclerosis), as well as atherosclerosis and cancer metastasis.

What they have in common is that all of them share biochemical mechanisms. A key one among them is the action of an enzyme family (PLA2) that initiates the production of a cascade of pro-inflammatory mediators involved in the induction and propagation of the diverse inflammatory diseases.

In Prof. Yedgar's lab at the Hebrew University, he and his associates have designed and constructed an entirely novel synthetic generation of drugs that control the PLA2 activity and the subsequent cascade of pro-inflammatory mediators, thereby providing multi-functional, anti-inflammatory drugs (MFAIDs).

MFAIDs have shown excellent safety and were found efficient in treating diverse inflammatory/allergic conditions in animal models, using different ways of administration - oral, rectal, intravenous, inhaled and injected. These conditions included sepsis, inflammatory bowel diseases, asthma and central nervous system inflammation.

In particular, in two clinical studies MFAIDs have been shown to be safe and efficient in treating contact dermatitis, when incorporated into skin cream, and allergic rhinitis, when administered as a nasal spray.