University of Zürich

Neurotune Ag

Stefan Hettwer

Birgit Dreier

Jan Willem Vrijbloed

Peter Sonderegger

Susanne Sales

Stefan Kucsera

Raymond Reif

Marc F Bolliger

Beat Kunz

Daniel Lüscher

Alexander Stephan

Kazumasa Miyai

Modified agrin fragment having in vivo activity, comprising at least the domains LG2 and LG3 of human agrin in covalently interlinked form and modified in such a way that the fragment cannot be cleaved by neurotrypsin for use as medicament.

Modified agrin-fragment capable of restoring muscle strength for use as a medicament

The invention relates to a method for determining whether a compound is a neurotrypsin inhibitor, characterized in that the compound is incubated together with neurotrypsin, a variant thereof or a fragment comprising the protease domain and with a protein or peptide comprising agrin, a variant thereof or a fragment comprising the &#x3b1;- or the &#x3b2;-cleavage site of agrin, in an aqueous buffer solution, and the amount of cleavage of agrin is measured. Additionally, the invention relates to inhibitors of neurotrypsin found by this method, in particular to compounds of formula wherein Haland Halare fluorine, chlorine or bromine, and the use of such inhibitors for the treatment and/or prophylaxis of diseases caused by deficiency of synapses, for example skeletal muscle atrophy, schizophrenia, and cognitive disturbance.

Method for determining inhibitors of neurotrypsin

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Zurich, Switzerland

Stefan Hettwer