Thomas, Craig (NHGRI)
Shen, Min (NHGRI)
Auld, Douglas (Novartis Institutes for BioMedical Research)
Schoenen, Frank (The University of Kansas)
Coombs, Thomas (University of Arkansas)
Tanega, Cordelle (NHGRI)
This technology includes small molecule inhibitors of the cdc2-like kinase (Clk) and Dyrk kinase which can restore splicing outcomes within many dysregulated splicing events potentially reversing phenotypes associated with diseases associated with abnormal splicing. The Clks regulate the alternative splicing of microtubule-associated protein tau and are implicated in frontotemporal dementia and Parkinson's disease through the phosphorylation of splicing factors (SF). DyrklA is proposed to play a critical role in the development of Down Syndrome (DS) due to the location of the DyrklA gene on Chromosome 21 in the Down Syndrome critical region. Inhibitors of Clk and Dyrk isoforms may alter important dysregulated splicing events and could prove to be useful agents in disease phenotypes characterized by abnormal splicing.
There are no existing therapies based upon splicing regulation and therapies for diseases such as Down syndrome, Alzheimer's Disease and other diseases associated with incorrect splicing.