Preclinical programs
     
The mitochondrion and the permeability of its membranes seem to play an important part in the cellular decision making that leads, irreversibly, toward the execution phase in cellular death processes. Congenia believes that targeting mitochondrial dysfunction through inhibition of the mPTP offers opportunities to discover and develop novel therapies for a wide range of diseases.

Currently, in our most advanced discovery programs we have identified compounds that have demonstrated in vitro and in vivo activity which we plan to develop initially addressing reperfusion injury. We also intend to initiate additional discovery programs in disease areas we believe to be well suited to our approach.

Congenia is looking to expand its discovery and development program through partnerships which will provide access to development and commercialization capabilities necessary to apply our platform to all potential therapeutic areas.

Congenia's discovery efforts benefit from integrated teams focused on mPTP biology, medicinal chemistry, clinical and translational medicine. We have also formed important research partnerships with investigators in the academic community, sharing mPTP inhibitors to develop new disease pathway knowledge.

If you would like to partner with Congenia in a research collaboration please consult our Collaborations section.

Congenia's mPTP inhibitors prevent mitochondrial calcium overload

Congenia's proprietary mPTP inhibitors increase the capacity of isolated mitochondria to retain calcium.

The Calcium Retention Capacity (CRC) of purified mouse liver mitochondria is determined by measuring the point at which pulse-loaded calcium is released from the mitochondria. After the addition of a pulse of calcium (10microM) the extramitochondrial fluorescence increases. As the mitochondria take-up the calcium the fluorescence signal decreases.

Calcium is continually loaded into the mitochondria until there is a sudden, large, increase in calcium fluorescence which indicates complete release of the stored calcium due to opening of the mPTP.

Inhibition of the mPTP, with Cyclosporin A or our proprietary inhibitors can increase the capacity of mitochondria to retain calcium and thus protect the mitochondria from calcium overload in stress situations. Extramitochondrial calcium is measured by the flurescence of calcium green.

mPTP inhibitor efficacy in an in vivo model of Acute Myocardial Infarction

In vivo studies using a Rabbit model of Acute Myocardial Infarction clearly demonstrate that two diverse mPTP inhibitors (Congenia’s proprietary inhibitor and cyclosporine A) are able to attenuate lethal reperfusion injury and reduce infarct size when administered just prior to heart reperfusion.

Rabbits were subjected to Left Anterior Descending (LAD) coronary artery occlusion for 30 mins followed by 4 hrs of reperfusion. Congenia’s mPTPi and cyclosporine A CsA were administered by i.v. bolus 5 mins prior to reperfusion. Infarct size and area at risk were determined by measuring TTC and Evans blue-stained heart slices.