Cell Permeable Peptides for the Treatment of Allergy, Asthma and Inflammatory Related Diseases

The Invention Novel cell permeable peptides that fuse a membrane permeation sequence to a functional sequence were developed. These cell-permeable peptides are capable of blocking signal transduction pathways in mast cells, preventing mediator release and the subsequent inflammatory reactions. The cell-permeable peptides comprising the C-terminal end of Galpha i3 could serve as a potent inhibitors of both IgE dependent and IgE independent signaling pathways and therefore as a potent blockers of the release of both the immediate and the late-phase inflammatory mediators. The use of peptides as novel therapeutic tools directed against intracellular targets in mast cells represents a breakthrough in the treatment of allergic and inflammatory reactions. A battery of peptides was developed in search of lead molecules capable of effectively blocking mast cell degranulation. Biochemical modifications, structural analyses and point mutations carried out in a series of prime candidates led to the identification of several active molecules, including the lead molecule ALL1.
The Need Allergy refers to conditions in which a wide range of biologically active substances cause tissue inflammation and organ dysfunction. Allergy is a major cause of morbidity and medical expenses in developed countries, affecting about 30% of the world population. Allergic diseases, including nasal allergy, asthma, ophthalmic and skin allergies are among the most common diseases encountered by physicians in their clinical practice. Central players in the allergic and inflammatory reactions are the mast cells. These cells are packed with 500 to 1000 granules that store the mediators of the inflammatory reactions. Mast cell-derived mediators possess all the properties required to induce the itching, swelling, coughing and choking associated with the allergic attack, as well as to trigger the onset of the delayed inflammatory reactions. Allergies including asthma and allergic conjunctivitis are on the rise most especially in urban areas, mirroring changes in environmental pollutant levels. Most drugs for allergies treat the symptoms hence, there's a great need for innovative drugs that will inhibit the allergic reaction at a very early stage and prevent the whole range of delayed inflammatory reactions.
Potential Applications Treatment of various allergic diseases:
• Asthma
• Skin allergies including acute urticaria (hives) , atopic dermatitis (eczema) and contact dermatitis
• Allergic Eye Disease (conjunctivitis)
• Chronic inflammatory diseases including bowel diseases such as Crohn’s disease, interstitial cystitis, and multiple sclerosis

Advantages The drugs are likely to prevent the onset of both the acute and the delayed phases of the inflammatory reaction. The drugs are effective against both immunological (IgE-dependent) and non-immunological (IgE-independent) inflammations including Neurogenic inflammation and T cell dependent inflammation. Novel mechanism of action.

Stage The novel peptide ALL1 has proven to be effective impediment of mast cell degranulation and allergic reactions both in vitro and in vivo. This is achieved by blocking the function of the G-protein (Gi3) that was found to be a key player in mast cell activation. Gi3 is activated either directly by numerous allergens that act as receptor mimetic agents or by receptors to mediators that are released upon mast cell activation and consequently amplify tremendously the allergic and inflammatory reaction.

Anti allergic activity was demonstrated in animal models for different allergic conditions: Skin tests in rats, conjunctivitis model in mice, asthma models in rats and mice. ALL1 was also found to inhibit airway hyperresponsiveness, a hallmark feature of asthma. Acute and 14-day repeat dose toxicity studies demonstrated minimal toxic effects.

Patent Granted and pending Tech Transfer Officer Dr. Tamar Raz Office: +972-3-6406580 Fax: +972-3-6406675 Mail: [email protected]

Inventor(s): Ronit Sagi-Eisenberg

Type of Offer: Licensing



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