Other

The General Hospital Corporation

University System of Maryland

Synaptic Research, LLC

Paul S Fishman

George A Oyler

Randall L Kincaid

Yien Che Tsai

Robert H Brown, Jr

Yen Che Tsai

Betsy A Hosler

Jonathan W Francis

A system and method for identifying aneurotoxin inhibitor employing aneurotoxin substrate complex having a peptide substrate, preferably SNAP-25, a reporter domain on one side of said peptide substrate and an immobilization domain on the opposite side of said peptide substrate. Theneurotoxin inhibitor is identified by its ability to decrease the relative amount of cleaved complex, detected through measuring a decrease in complex bound to a solid support. The method of the present invention also utilizes novel cells that express aneurotoxin substrate complex. Also provided are novel stable cell lines that express thetoxin substrate complex and viral vectors capable of efficiently expressing an active light chain of the BoNT within mammalian cells.

Methods for identifying inhibitors of botulinum neurotoxins

A system and method for identifying a botulinum neurotoxin inhibitor employing a botulinum neurotoxin substrate complex having a peptide substrate, preferably SNAP-25, a reporter domain on one side of said peptide substrate and an immobilization domain on the opposite side of said peptide substrate. The botulinum neurotoxin inhibitor is identified by its ability to decrease the relative amount of cleaved complex, detected through measuring a decrease in complex bound to a solid support. The method of the present invention also utilizes novel cells that express a botulinum neurotoxin substrate complex. The methods of the present invention are adapted for cell based screening to monitor the catalytic activity of a BoNT in living cells and to identify molecules that inhibit the catalytic activity of a BoNT in living cells. Also provided are novel stable cell lines that express the botulinum toxin substrate complex and viral vectors capable of efficiently expressing an active light chain of the BoNT within mammalian cells.

A system and method for identifying aneurotoxin inhibitor employing aneurotoxin substrate complex having a peptide substrate, preferably SNAP-25, a reporter domain on one side of said peptide substrate and an immobilization domain on the opposite side of said peptide substrate. Theneurotoxin inhibitor is identified by its ability to decrease the relative amount of cleaved complex, detected through measuring a decrease in complex bound to a solid support. The method of the present invention also utilizes novel cells that express aneurotoxin substrate complex. The methods of the present invention are adapted for cell based screening to monitor the catalytic activity of a BoNT in living cells and to identify molecules that inhibit the catalytic activity of a BoNT in living cells. Also provided are novel stable cell lines that express thetoxin substrate complex and viral vectors capable of efficiently expressing an active light chain of the BoNT within mammalian cells.

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Disclosed is a 68 kD recombinant hybrid protein comprising an enzymatically active Cu/Zn superoxide dismutase ('SOD-1') moiety and a tetanus toxin fragment C ('TTC') moiety, wherein the TTC moiety selectively delivers the hybrid protein into neurons, and the SOD-1 moiety retains substantial enzymatic activity, following neuronal uptake. Also disclosed are a DNA expression vector encoding the hybrid protein.

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Baltimore, MD, United States of America

Paul S Fishman