Treatment of alzheimer disease by modulation of synapsins

US6444201B1 · kind B1 · utility

Assignees

• The Rockefeller University · US
• Brighan and Women's Hospital · US

Inventors

• Hui-Quan Han · Thousand Oaks, US
• Paul Greengard · New York, US
• Kenneth S. Kosik · Belmont, US
• Adriana De Souza Ferreira · Boston, US

Key dates

• Filing date: May 13, 1996
• Grant date: Sep 3, 2002
• Expiry date: May 13, 2016

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P25/28
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The role of synapsin II in both the reformation and the maintenance of synaptic connections in cultured hippocampal neurons can be the basis of therapy for neurodegenerative disorder, particularly Alzheimer disease, which involve the disruption of synapses. When synapsin II expression in neurons is blocked by antisense synapsin II oligonucleotides, the ability of hippocampal neurons to reform as well as to maintain synapses is severely disrupted. Antisense suppression of synapsin II after axon formation but immediately before synaptogenesis prevents synapse formation. Suppression of synapsin II after synaptogenesis disrupts the majority of existing synapses. Re-expression of synapsin II in synapsin deficient neurons achieved after removing the antisense oligonucleotides leads to the re-establishment of synaptic connections, providing direct evidence that synapsin II is required for the maintenance and/or restoration of synapses. Thus, therapeutic methods based on the reformation and the maintenance of synapses, including delivery of the synapsin cDNAS or proteins into the patient's nervous system, use of the synapsin cDNAS to promote the synapse forming ability of cells for graftin…