A UK University has developed a rapid phenotypic screen for anti-fibrotic activity
The UK university has developed an innovative assay to measure the anti-fibrotic activity of test compounds and wishes to commercialise this under a licensing agreement, research cooperation agreement or technical cooperation agreement.
Companies or organisations with experience in commercialising products and taking them to market or who would need this type of assay to further develop a product which is in developmental stage under a licensing agreement, research cooperation agreement or technical cooperation agreement.
Fibrosis is the accumulation of extracellular matrix proteins due to chronic inflammation. It is the common underlying pathology in several chronic and progressive diseases, and accounts for 42% of all deaths worldwide. Common examples are idiopathic pulmonary fibrosis, hepatic fibrosis (cirrhosis), kidney fibrosis, heart fibrosis, scleroderma, Dupuytren’s contracture and Peyronie’s disease, although any organ in the body can be affected. Pathophysiology is complex and multi-factorial. There are limited drug treatments available for fibrosis and there is no medical treatment with significant efficacy and safety available. There are two drugs that are approved for the treatment of fibrosis, but their mechanisms of action and targets are not well understood. Further, they only halt the disease progression, rather than providing a cure. Although potential targets for new active compounds have been proposed, none have resulted in an effective pharmaceutical. The university has developed an innovative assay that uses in-cell ELISA (a specific quantitative assay to measure intracellular protein concentrations with no need for cell lysis) to monitor the inhibition of fibrotic activity by a test compound. This assay uses a phenotypic approach to screen compounds for antifibrotic activity. Primary human fibroblasts cultured in vitro can be induced to transform into myofibroblasts, an indicator of fibrotic activity in vivo. The change in cell phenotype is monitored by In-Cell ELISA of phenotypic markers. Inhibition of the transition by a test compound is evidence of an anti-fibrotic action. This novel, rapid and robust assay can be used to screen a large library of potential drug candidates at low cost. The assay will be most cost-effective to screen existing pharmaceuticals approved by the FDA (Food and Drug Administration) for other indications. The target-independent nature of the assay makes it ideal for identifying synergistic effects, where two compounds used in combination, acting on different targets, have an anti-fibrotic activity greater than the sum of their individual actions. Such a combination therapy will be necessary in order to overcome the redundancy in the wound-healing pathways underlying fibrosis. Assays are conducted on 96-well plates, with a capacity for testing up to 30 drugs, compounds or combinations. Any drug or compound showing a positive effect can be further investigated by conducting an additional assay to create a dose response curve. Two compound concentration response curves can be conducted per 96-well plate. Screening of available FDA-approved drugs has identified a new combination therapy for Peyronie’s disease. A patent application has been filed and the method is available for licensing by a commercial partner. The university would also be interested in working with partners under research cooperation agreement or technical cooperation agreement.
Advantages and innovations
This phenotypic assay rapidly identifies anti-fibrotic activity using an entire cell fibrosis model, independent of the mechanism of action. This target-independent method is suited for the rapid screening of existing compound libraries. Development of an effective fibrosis treatment using conventional target-based methods have been unsuccessful due to the multiple redundancy built into the wound healing process that leads to fibrosis. The university’s innovative method can identify the combination therapies necessary to overcome this effect and produce an effective treatment. The University’s experienced team can provide knowledge exchange to enable a partner organisation to conduct the assay, or they can provide the assay as a service to screen a partner’s drug candidate libraries.
Available for demonstration
Intellectual Property Rights (IPR)
Secret Know-how,Patent(s) applied for but not yet granted
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