Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down’s syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial
A Spanish research group (Rafael de la Torre/ Mara Dierssen) has published the outcome of their phase 2 trial for improvement of cognition in individuals with Down’s syndrome. (Lancet Neurol 2016; 15: 801–10). The results of the trial look promising, but it is not possible to recommend the treatment for general use until further, larger clinical trials have been completed.
Our collaborator at University College London, Dr André Strydom, Reader in Intellectual Disabilities, explains the significance of this study here:
“Recent progress in our understanding of the causes of brain problems has resulted in the identification of potential treatment options for some aspects of the learning difficulties associated with Down syndrome. If these treatments are effective, it will have significant implications for individuals, their families, and health services, because even modest improvements in long-term outcomes could lead to a significant reduction in the lifetime need for support. In that context, this is a ground-breaking and much anticipated study which could have significant impact on the management and longer-term outcomes of individuals with Down syndrome.
Epigallocatechin-3-gallate (EGCG), a naturally occurring component of green tea, was initially identified in animal model studies as a potential treatment for the learning difficulties of Down syndrome. EGCG can suppress an enzyme called DYRK1A which is produced excessively in Down syndrome (the DYRK1A gene is on chromosome 21). Animal and laboratory studies have shown that over-activity of this enzyme has many effects, and that it is partially responsible for the memory and learning difficulties in Down syndrome.
The authors therefore undertook a phase 2 randomised trial of EGCG in combination with cognitive training against cognitive training alone to see if it could improve cognitive outcomes in adults with Down syndrome. (A phase 2 trial is a relatively small scale “first-look” trial, to see whether a new treatment works well enough to be tested in a larger phase 3 large scale trial, and to learn more about potential effects of a potential treatment).
This trial showed that EGCG treatment was safe and had low levels of side-effects. The authors also identified the potential for positive outcomes with EGCG treatment in combination with cognitive training on some measures of cognitive ability, as well as a potential improvement in functional ability. These improvements were relatively modest, but brain imaging showed better brain connectivity in those that had the treatment. The authors also reported that the treatment had a measurable effect on markers of DYRK1A activity, such as cholesterol and homocysteine levels.
Overall the results of this trial are promising and suggest the possibility of improving longer-term outcomes in individuals with Down syndrome using EGCG together with cognitive training. However, the trial is typical of first-look trials, which include a relatively small number of individuals who are treated for a short period. It therefore cannot provide a definitive answer about whether longer-term treatment is worthwhile, and cannot exclude the possibility of important longer-term side-effects of the treatment. It is also important to note that it is not possible to make any conclusions (whether positive or negative) about the potential effects in children as the treatment trial only included adults. For these reasons, it is not possible to recommend the treatment for general use until further, larger clinical trials have been completed.
This study has however paved the way for further clinical trials of this type of treatment to improve learning difficulties in individuals with Down syndrome.”
Dr André Strydom, Reader in Intellectual Disabilities, University College London