This project is based on several experimental findings that identify a Bcl-2 family protein as important for mast cell survival in allergic reactions. Inhibition of this protein leads to a decreased number of mast cells in inflamed tissue

These findings strongly point out the pro-survival gene A1/Bfl-1 as a pivotal mediator of IgE induced cell survival, a mechanism that plays a crucial role in regulating the inflammatory cascade. We thus validate Bfl-1 as a promising new drug target for the development of treatment regimens for IgE dependent allergic diseases.

Working hypothesis & treatment concept:

Since, in allergic diseases, mast cell numbers are increased at sites of inflammation, pharmacologic intervention into the survival (or apoptosis) of mast cells is considered to be a promising strategy for management of allergic disorders.

We have identified A1/Bfl-1 as a pivotal mediator for the IgE receptor activation-induced mast cell survival. Consequently, our treatment hypothesis is based on the rationale that inhibition of this protein will be a potent means to influence the presence of the effector cells (mast cells) causing the pathological symptoms in the inflamed tissue.


Experimental data:

Our experiments demonstrate that the process of mast cell survival and regranulation after IgE receptor activation depends on the pro-survival gene A1/Bfl-1.


The conclusion is based on three major lines of evidence:

1. Activation of mast cells through Fc?RI results in strong induction of A1/Bfl-1 mRNA and protein and cell survival after growth factor deprivation.

2. A1-deficient mouse mast cells do not survive the allergic activation, but release granule mediators similar to the wild-type control.

3. A1-deficient mice that are sensitized and provocated with allergen exhibit a reduced number of regranulated mast cells as compared to the littermate controls, and diminished ear swelling after active cutaneous anaphylaxis, a reaction resembling an allergic inflammatory response.

 

Early Stage

The patents and IPR protect:

• a method to treat mast cell mediated inflammatory disorders in mammals comprising regulating the longevity and activity of activated mast cells by inhibiting the expression and/or function of the anti-apoptotic A-1/Bfl-1 gene or gene product, and
  
• the development and use of a compound capable of inhibiting the expression and/or function of the anti-apoptotic A-1/Bfl-1 gene or gene product for the manufacture of a medicament for treating mast cell mediated inflammation in human tissues.
  

Following the acquisition of the exclusive worldwide IP rights associated with the invention, Innoventus Project AB has pursued a proactive patent strategy to obtain a strong and basic protection, both technically and geographically, to secure the IPR to the A1/Bfl-1 drug target and the use thereof for development of a medical treatment.

Innoventus' role and competence is in early stage project development and an industrial partnering is essential for the further development of this project.

For that reason Innoventus is seeking an industrial partner to manage the project during its subsequent phases.