4628

New Cyclic Peptide Inhibiting Integrin-alpha4 for the Treatment of Multiple Sclerosis ( VISABRON)

Lazarovici Philip, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

Category

Life Sciences and Biotechnology   

Keywords

Peptide, Bioavailability, Autoimmune diseases

Current development stage

For Pharmaceutical development: TRL4 - PoC&Safety of candidate device or system is demonstrated in a defined lab or animal model

 

Application

Uveitis is inflammation inside the eye, specifically affecting one or more parts of the uvea. It is induced by eye infiltration of T lymphocytes (T cells) capable of recognizing retinal antigens. Uveitis is estimated to be responsible for approximately 10%-20% of blindness in the United States. Its global treatment market was valued at $478 million in 2018, and is projected to reach $687 million by 2026, registering a Compound annual rate of growth (CAGR) of 4.6% from 2019 to 2026.

Today, uveitis is treated mostly by steroids and immunosuppressive medications, which have significant unwanted side effects. Therefore, there is an unmet clinical need to develop novel "corticosteroid like" drugs, targeting activated T cell lymphocytes which infiltrate the eye.

Calreticulin is a membranal protein of activated T lymphocytes involved in inflammation by increasing lymphocyte intracellular calcium and modulating gene activity. The invention presents a novel corticosteroid partial mimetic cyclic peptide, an antagonist of Calreticulin, as a potential treatment to uveitis, which may overcome the challenges of the current treatments.

Our innovation

The suggested new drug for uveitis is a novel backbone cyclic peptide which acts by inhibiting the Calreticulin function. Calreticulin is expressed at the cell surface of activated human peripheral blood T lymphocytes, its level increases after inflammation making Calreticulin an important anti-inflammatory target. The researchers developed a lipophilic prodrug of the peptide with enhanced properties to permeate through biologic membrane, enabling different administration modalities, including oral administration.

Opportunity

Uveitis is mostly treated today by corticosteroids. Clinicians continue to use corticosteroids today, even though they are aware of the unwanted side-effects, because of its success to decrease inflammation. The present invention for the treatment of uveitis aims to keep the therapeutic effect of corticosteroids, without the unwanted side effects. It suggests a novel peptide that demonstrates a corticosteroid-like activity, in a more specific mode of action which will potentially reduce the side effects. In preliminary studies using EAU mice model, repeated treatment using a lead peptide has reduced by 50% the inflammatory response, measured by EAU retinal score.

 

 

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Keren-Or Amar
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