BioWorld International Correspondent

PARIS - The Marseille-based biotechnology company Trophos, which is developing therapies for a number of neurodegenerative diseases, has published initial research results on the discovery of a new class of differential γ-secretase inhibitors, which it describes as "an important step in its research program into Alzheimer's disease."

Trophos pointed out that, while most research into Alzheimer's targets the neurotoxic role of amyloid plaques and the Aß peptide, other toxic peptides originating from the cleavage of the amyloid precursor protein (APP) by γ-secretase have also been identified. Molecules that inhibit ß or γ secretase are potential blockers of the production of these peptides and as such are drug candidates for the treatment of Alzheimer's.

Inhibitors discovered in earlier research could not be exploited therapeutically, because they also inhibited a very similar signaling pathway for another protein, called Notch, which is vital for embryonic development and hematopoiesis. But the new class of γ-secretase inhibitors discovered by Trophos leaves the Notch pathway intact, thus opening up the possibility of them being developed as therapeutic compounds.

The discovery is to be published in the May edition of Nature Cell Biology, under the title "New protease inhibitors prevent γ-secretase-mediated production of Aß40/42 without affecting Notch cleavage."

Trophos claims to be the first drug discovery company specializing in compounds that prevent neuronal cell death, and Alzheimer's is one of three pathologies it is targeting, the others being motoneuron diseases (spinal muscular atrophy in children, and amyotrophic lateral sclerosis in adults) and Huntington's disease (a hereditary form of chorea). All three programs are at the research stage at present, and Trophos does not expect to embark on preclinical development until next year at the earliest.

The company completed an initial funding round in early 2000 and is due to close another in a few weeks.

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