Pharmasum is focusing on dementia in Down syndrome where the genetic link to our drug target is strong and the clinical chance of success is high due to a less heterogenous population compared to Alzheimer´s disease in general.
Down syndrome individuals are especially prone to developing dementia and represent the largest group of dementia patients below 50 years of age (Hanney et al 2012; Lancet). Down syndrome (DS; Trisomy 21) is the most common genetic disorder globally, affecting as many as 1 out of 800 live born children, with almost 6 million individuals worldwide. The disorder is caused in the most cases by the presence of a third copy of chromosome 21. The dysregulation of a number of genes affects the development and health of DS individuals causing problems with cognition, learning and memory. Individuals with DS develop Alzheimer’s disease dementia at an early age. The Down syndrome Critical Region (DSCR) on chromosome 21 includes genes for amyloid precursor protein (APP) and DYRK1A, and these are over-expressed in people with DS.
The brains of almost all individuals with Down syndrome have significant levels of plaques and tangles, hence, abnormal protein deposits considered Alzheimer's hallmarks that combined contribute to the development of dementia
The protein kinase enzyme DYRK1A is considered the key brain factor that leads to the primary developmental cognitive impairment. Pharmasum is developing a novel therapy for dementia in DS, a clinical indication where current treatment options are lacking. The DYRK1A protein kinase inhibitor PST-674 represents a unique innovation in a global market, serving an extremely high unmet medical need. The value creation of the technology for society and patients is potentially vast.