Introduction

The present invention concerns an RNA interference mediated therapy for neurodegenerative diseases associated with abnormalities of microtubule-associated protein tau (“tauopathies”).  The RNA interference-mediated therapy uses siRNAs to target neurodegenerative diseases associated with abnormalities of microtubule-associated protein tau (“tauopathies”), including FrontoTemporal Dementia, Progressive Supranuclear Palsy and Alzheimer’s Disease.

Technical features

MAPT is the gene coding for protein tau, which has a key role in neuronal development and health. Tau aggregates are hallmarks of Frontotemporal Dementia and other tauopathies like Progressive Supranuclear Palsy and Alzheimer’s Disease. Tau aggregation is in many cases dependent on the altered inclusion of exon 10 in MAPT mRNA. The invention consists in siRNAs that specifically target exon 10-containing MAPT mRNA, thus avoiding tau aggregation.

Possible Applications

• Therapy for neurodegenerative diseases;
• Therapeutic agent for the cure of Frontotemporal Dementia with Parkinsonism linked to Chromosome 17;
• Therapeutic agent effective in the treatment of neurodegenerative diseases associated with abnormalities of MAPT gene encoded protein tau.

Advantages

• Specifically targets only altered MAPT mRNA;
• No cures are presently available for tauopathies (orphan drug);
• RNA therapy;
• Synthesis of modified RNAs easily done in bulk by companies;
• Several siRNA-based drugs recently approved;
• Brain-specific delivery of siRNAs being developed by companies and academia;
• No isoform-specific siRNA patented so far.