Neuroprotectants

Stroke is one of the top three causes of death and disability in the developed world of the population aged between forty and eighty years with an increasing incidence due to an aging population. Approximately eighty-five percent of strokes are ischemic, which result from the occlusion of major cerebral arteries due to embolic or thrombotic events. This leads to a lack of blood flow and a decrease of oxygen supply, nutrients and energy to the affected area. Fifteen percent of strokes instead are haemorrhagic. This project focuses on ischemic stroke.

 

The stroke market is scarcely met with effective drugs despite its strong clinical need. Treatment is offered in two types:

  • drugs involved in the clotting process (thrombolytics)
  • drugs that work on the state of neuronal tissues (neuroprotectants)

 

Thrombolysis involves the use of tPA (tissue plasminogen tissue activator) to restore blood flow to the affected area by dissolution of the clot. Despite the effectiveness of this therapy, its use is limited as the tPA must be administered within three hours after the event, during which time a differential diagnosis must be performed using UT scans, to determine the etiology of the stroke. Indeed, if the stroke results haemorrhagic, the use of tPA is strongly not recommended. Neuroprotectants are a completely different approach, in which the pharmacological agent must interfere with a series of biochemical mechanisms that follow the stroke to prevent cell death. Many new compounds have been developed as neuroprotectants, yet all have failed during clinical trials even after showing unquestionable efficacy in animal models of ischemia. These failures have led to a comprehensive review of the validity of animal models and the production of the “STAIR criteria” guidelines (Stroke Therapy Academic Industry Roundtable, 1999-2001) for the preclinical development of this therapeutic class of compounds.

 

Our research has two main objectives:

  • to create an integrated system that collects, processes and permits the availability of biological data from gene expression arrays (genomics and transcriptomics) images of two-dimensional gel electrophoresis (proteomics), spectrometric mass analysis, biochemical and molecular analysis, morphological images (OM and SEM), in animal models of cerebral ischemia which consents the identification of the most predictive parameters of animal models to the human pathology.
  • to evaluate the impact of new proprietary molecules on other molecular mechanisms involved in the development of the ischemic event and identify the possibility to fill this gap with therapeutic drugs that interfere with these oxidative mechanisms with a high bioavailability in the site of action.