Improving cognitive and functional performance in Down syndrome with a natural compound found in green tea
There is no cure for Down syndrome. Medicine has been successful insofar as it has extended the lifespan of people with this syndrome. Nevertheless, major cognitive and functional abnormalities persist. In fact, Down syndrome is the most frequent cause of genetic mental retardation and affects one in every 1000 people in the world. But if people with Down syndrome live longer, what can they expect in terms of quality of life? Their limited cognitive and functional performance up to adulthood courses later with progressive neurodegeneration such as that seen in Alzheimer disease. Wouldn’t it be worth working on?
This is the question that the researchers of the IMIM Clinical Research Group on Integrated Pharmacology and Systems Neuroscience, led by Rafael de la Torre, together with the Cellular and Systems Neurobiology Group, led by Mara Dierssen, of the Barcelona Genomic Regulation Center with the support of several institutions and foundations, such as the Catalan Down Syndrome Foundation, the Jérôme Lejeune Foundation, the Spanish Federation of Institutions for Down Syndrome (DOWN ESPAÑA) and the Carlos III Institute. Researchers with extensive experience in the area of neuroscience and in the neurobiology of Down syndrome worked side-by-side with clinical specialists in neuroscience, pharmacologists, biochemists, neuropsychologists, neurophysiologists and specialists in neuroimaging.
A flavonoid that occurs naturally in green tea, called epigallocatechin gallate (EGCG), has been seen to act on neuron connections and to have a safe and beneficial effect on learning ability and the ability to memorize in people with Down syndrome.
The result of this collaboration was a clinical trial that showed for the first time that it is possible to talk about an effective treatment for improving cognitive performance and functionality in people with Down syndrome. The encouraging message comes through a new substance, present in green tea, which acts on neuron plasticity and improves memory, attention and learning ability. The goal is to develop a therapy that improves not only the cognitive phenotype in children and young adults but that may eventually slow the progression of neuron degeneration that these people share with Alzheimer patients.
Green tea extract to inhibit an overexpressed gene
A flavonoid that occurs naturally in green tea, called epigallocatechin gallate (EGCG) is the major finding of the study. It has been seen to act on neuron connections and to have a safe and beneficial effect on learning ability and the ability to memorize in these people. EGCG has the ability to modulate expression of the gene Dyrk1A, which is overexpressed in Down syndrome and is linked to neurodegeneration in Alzheimer disease.
It is not a “miracle” drug; it is a substance that favors the physiological processes of neuron plasticity.
Administration of ECGC has already shown quite convincing results in previous preclinical studies in mice that partially model Down syndrome to determine the effect on cognitive performance of inhibiting the gene Dyrk1A using the new substance. These results were repeated in a very encouraging manner in the translation of the phase-I pilot study in humans, which began in 2010 with 31 volunteers and is funded by the Jérôme Lejeune Foundation, and again, the phase-II clinical trial with 87 volunteers aged between 16 and 34 years (TESAD study) over 19 months showed that it was possible to achieve a major change in quality of life, in cognitive improvements and in the resulting personal autonomy.
Medication and cognitive stimulation
Administration of a food supplement with 400 to 800 mg of EGCG (depending on the participant) in half of the patients (placebo in the other half) was supplemented with a cognitive stimulation protocol provided by the online platform, FesKits, which consists of three weekly sessions of 40 minutes each to train memory, attention, language and executive functions. After a year-and-a-half of giving blood samples, undergoing analyses of body composition, functional neuroimaging tests, neurophysiological tests and neuropsychological tests, the participants achieved a significant improvement in their ability to learn and memorize information.
The next steps face the challenge of achieving even better results by starting this treatment early, in children with Down syndrome, in order to take advantage of the greater plasticity of the brain, which is still developing. Children who will be able to have a long life with the expectation of greater functionality and autonomy.
De la Torre et al. ‘Safety and efficacy of cognitive training plus epigallocatechin-3-gallate for cognitive improvement in young adults with Down syndrome (TESDAD): a double-blind, randomised controlled, Phase 2 trial”. Lancet Neurology. 6th June 2016.