The purpose of this project is to interest the European pharmaceutical industry in new molecules of marine origin relating to three complementary fields: antitumoral, antiviral (AIDS, herpes, dengue) and immunomodulatory substances. The project is based on the great originality of substances present in marine organisms, mainly invertebrates. Moreover, a considerable number of species have not yet been studied for their pharmacologic aspects.
The success of this project depends mainly on the capacity of the participating teams to carry it out effectively (Cf. the presentation letter attached to the application) and the scientific options taken: 1. Two branches have been retained for study: sponges and tunicates (ascidians). Sponges have provided the largest number of original marine molecules, including several of pharmacologic interest. The ascidians, composed of fewer species, were chosen because of the exceptional frequency of nitrogenous metabolites which often possess high activity. Moreover, both of these branches consist of filtering organisms, and it has often been suggested that several pharmacologically important metabolites come from their associated microorganisms. This is a considerable advantage in the perspective of biotechnological production of interesting molecules. We have selected a variety of sampling areas: two widely separated tropical zones (the Vanuatu and the west coast of Madagascar), for which we have noted an important, original biological potential; a warm temperate zone (the Mediterranean), where sponge collection at Ustica Island has provided several interesting leads which will be followed up in the project; and a cold temperate zone (the Atlantic coast of France) which is still unexplored with respect to potentially antiviral and immunomodulatory substances.
2. The marine environment appears to be especially rich in antitumoral molecules (several marine substances are now at the clinical trial stage) and to a lesser extent in antiviral molecules, though this field has been less studied. The immunomodulatory field is relatively unexplored and thus propitious for discoveries.
3. Particular emphasis has been given to the quality of pharmacologic screening, which will be performed on collected species in order to ensure that chemical studies (extraction, purification, structural identification, synthesis or structural modulation) are not undertaken without a maximal chance of success.
For example, the proposed approach for antitumoral screening should allow us, in particular, to avoid those substances often present in marine organisms which are potentially too toxic.
4. The molecules, once identified, will be evaluated by in-depth pharmacologic studies in order to search for activities. In particular, animal experimentation will be untertaken, such as the use of xenografted human tumors for antitumoral studies. The most promising substances will be proposed to European industry.
Rhone-Poulenc Rorer (Paris) have agreed to provide expert evaluation of the antitumoral and antiviral substances and ensure their eventual development. Sandoz (Wien) has been contracted for immunomodulatory substances and we are waiting for a definitive reply.
Funding SchemeCSC - Cost-sharing contracts
84084 Penta Salerno