Fifty years ago, Jérôme Lejeune and colleagues verified a causal link between an extra copy of chromosome 21 and Down syndrome.  The exact mechanism by which the presence of this additional genetic material resulted in the cognitive impairment associated with Down syndrome remained unclear, hindering the development of medical therapies.  Nonetheless, the quality of life for individuals with Down syndrome improved tremendously in recent decades, as a result of improved health care, expanded educational and community opportunities, and the support of families and advocacy groups.  The life expectancy of those with Down syndrome more than doubled, highlighting the importance of the need to attain skills essential for independent living. In 2000, researchers working on the Human Genome Project fully sequenced human chromosome 21, spurring a renewed interest in exploring the pathogenesis of the intellectual impairments of Down syndrome. 

In the last six years, applying modern scientific tools and techniques, researchers made tremendous progress toward understanding and treating the cognitive issues associated with Down syndrome, successfully correlating cognitive impairment with specific genes, in specific cells, during specific stages of development. The identification of neurobiological pathways that are affected by the presence of additional genetic material now provides a rational basis for the development of drug therapies to address the cognitive impairment associated with Down syndrome. Scientists have demonstrated that a range of issues are altered in Down syndrome, including neuronal system development, neuronal transmissions and instructions necessary for neurons to “thrive” and have examined the impact of therapeutic compounds on memory and learning in mouse models of Down syndrome. These studies have yielded extremely encouraging results. This exciting progress is now prompting researchers and others to change their questions regarding therapies from “Can this be done?” to “When will this be done?”.

Research Advances

Research Revolution

A leading researcher in the genetics and neurobiology of cognitive dysfunction in Down syndrome, John Hopkins Professor, Roger Reeves, notes that plateaus in medical research can, at some point, give way to rapid advance. He feels Down syndrome cognitive research is at this stage now, and is extremely encouraged by the ongoing advances on several fronts in research institutions across the world. He remarked, “I never thought I would be in a position to say, ‘We are going to take therapies forward to directly treat Down syndrome.’ Now I think that is the case. We really are in the early stages of a revolution in understanding the basis for many of the features that occur in Down syndrome.”