TECHNOLOGY
Lead compound PST-674
Pharmasum Therapeutics has developed PST-674 by using advanced drug design technologies. In collaboration with The Arctic University in Tromsø (UiT), extensive X-ray crystallographic studies established the Structure-Activity Relationships (SAR), and subsequent Lead Optimization chemistry led to the development of the optimized small-molecule PST-674.
Drug target DYRK1A
The protein kinase DYRK1A (Dual-specificity tyrosine phosphorylation-regulated kinase 1A) is involved in several important processes in the brain and profoundly affects pathology in dementia. A high activity of DYRK1A leads to serious, structural changes in the brain resulting in cell death and development of dementia.
Dementia in Alzheimer´s and Parkinson´s disease
Since DYRK1A also plays a central role in other forms of dementia, further clinical trials will also include Alzheimer’s disease in the general population and dementia associated with Parkinson’s disease. Testing of PST-674 in large patient groups (Phase 3) will be done in collaboration with a partner.
DYRK1A gene is located on chromosome 21. The DYRK1A enzyme has been shown to be an important brain development factor. Its abnormal expression is thought to play a role in aberrant brain development, lifelong structural and functional neurological abnormalities, neural degeneration, and neuronal death (Weigel et al 2011).
In the case of individuals with Down syndrome, the 1.5x overexpression caused by Trisomy 21 results in retardation and moderate to severe cognitive impairment. DYRK1A is known to be involved at multiple sites of Alzheimer’s disease pathology in Down syndrome (Wiseman et al 2015); indeed, most people with Down syndrome show early onset of Alzheimer’s disease.
Pipeline
The protein kinase DYRK1A (Dual-specificity tyrosine phosphorylation-regulated kinase 1A) is involved in several important processes in the brain and profoundly affects pathology in dementia. A high activity of DYRK1A leads to serious, structural changes in the brain resulting in cell death and development of dementia.
DYRK1A gene is located on chromosome 21. The DYRK1A enzyme has been shown to be an important brain development factor. Its abnormal expression is thought to play a role in aberrant brain development, lifelong structural and functional neurological abnormalities, neural degeneration, and neuronal death (Weigel et al 2011).
In the case of individuals with Down syndrome, the 1.5x overexpression caused by Trisomy 21 results in retardation and moderate to severe cognitive impairment. DYRK1A is known to be involved at multiple sites of Alzheimer’s disease pathology in Down syndrome (Wiseman et al 2015); indeed, most people with Down syndrome show early onset of Alzheimer’s disease.
