Down syndrome: major strides forward in research

Publié le : 15 November 2013

 A few days away from the national Down Syndrome Seminar on 17 November, Valeurs Actuelles is devoting a double-page spread to the latest promising research into Down syndrome. In fact, on 17 October 2013, the IVth Sisley-Jérôme Lejeune International Awards Ceremony was held to celebrate the success of experienced and new scientists conducting research in the field of genetic intelligence disorders.

"Murine models of Down syndrome and guinea pigs presenting with recurrent memory and learning defects" appear to be one of the most promising avenues. The person responsible for this approach, Yann Hérault (1), one of the prize winners, reproduced "the majority of Down syndrome-related features […] in rodents" and demonstrated that only certain parts of chromosome 21 are involved in intellectual deficiencies. He also showed that the over-expression of cystathionine beta-synthase (CBS), an enzyme involved in neurotransmission, is responsible for memory defects in subjects with Down syndrome. 

Research conducted by a second recipient of the Sisley-Jérôme Lejeune Award, American scientist Lynn Nadel (2), also looks extremely promising. Mr. Nadel has worked "on the memory, and on the hippocampus to be precise, which has increasingly proved to play a key role in Down syndrome". For thirty years, he has "built bridges between new research tools including the creation of murine models and the development of brain imaging". Lynn Nadel is convinced that "it really is possible to make comparisons between humans and animals". 

In addition to the brain, Down syndrome also affects the heart, intestines, cranio-facial morphology and the hands. The 2012 Sisley-Jérôme Lejeune prize winner, Roger Reeves, discovered that over-expression with the SAG (Sonic Hedgehog) growth factor causes numerous problems and "succeeded in proving that a cerebellum treated with this molecule resumed its normal appearance". Furthermore, if SAG is injected into a mouse with Down syndrome on the day it is born, "at the age of 4 months, (equivalent to 25 to 30 years in humans), brain functions are considered to have ‘normalised’". 

Moreover, one last avenue of research seeks to partly inactivate the over-expressed chromosome 21 having previously isolated the "Xist" (X inactive specific transcript) gene and inserting it into one of the three 21 chromosomes in a person with Down syndrome. "Within a few days, [this gene] silences the expression of ten or so genes carried by this chromosome and essentially the one involved in intellectual deficiency". 

Overall, these advances are extremely revealing. For Roger Reeves they provide a "sound base" for the future and indicate that "results are imminent". 

Lastly, people with Down syndrome (approximately 65,000 in France) appear to be particularly prone to Alzheimer’s disease. Patient follow-up could shed more light on this subject, hence the comment stressed by a journalist that research into Down syndrome should have more financial support, which it currently only receives from private foundations such as the Fondation Jérôme Lejeune. Lynn Nadel pointed out that public research is seldom involved, if at all: "the amount allocated is extremely low compared to other disorders including certain rare diseases". 

(1) Yann Herault: Director of the Institut clinique de la souris (Murine Clinical Institute) within the Institut de génétique et de biologie moléculaire et cellulaire d’Illkirch (CNRS, Inserm) (Illkirch Institute for Genetics and Molecular and Cell Biology).        
(2) Lynne Nadel: University of Tucson (Arizona).

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