June 6, 2016

expert reaction to Down’s syndrome and green tea compound

Publishing in The Lancet Neurology journal a group of scientists have described their use of a particular extract of green tea to try to improve cognition of young adults with Down’s syndrome and report that the extract improved memory and behavioural aspects better than the placebo control.

Prof. David Nutt, The Edmond J Safra Chair and Head of the Centre for Neuropsychopharmacology, Imperial College London, said:

“It’s exciting that an understanding of the genetic neurobiology of Down’s Syndrome is leading to the possibility of disorder-specific treatments. Let’s hope that the promise of this early experimental study is confirmed in larger-scale trials and that others follow this approach as therapy targeting a number of the biochemical abnormalities that result from trisomy 21 might be the most effective way forward.”

Dr Marie-Claude Potier, Researcher on Down Syndrome and Neurodegenerative Diseases, Institut du Cerveau et de la Moelle (ICM) and Chair of the European College of Neuropsychopharmacology (ECNP) Targeted Network on Down syndrome and other genetic developmental disorders, said:

“Down syndrome (DS) is the most common genetic form of intellectual disability. It was long believed that the complexity of genetic challenge represented by the presence of a third chromosome 21 encoding hundreds of genes would be an insurmountable challenge to treatment. Nonetheless, research on cognitive impairment in DS from gene to behaviour to preclinical and clinical studies has taken a leap forward.

“The TESTAD study published in Lancet Neurology is a robust and important piece of work. It is the first double-blind, randomized and placebo-controlled phase 2 clinical trial combining cognitive training and administration of epigallocatechin-3-gallate (EGCG) for 12 months in more than 80 young adults with DS.

“De la Torre et al. show that EGCG and cognitive training improved some specific memory skills and adaptive behaviour as compared to individuals under placebo and cognitive training. Interestingly, positive effects persisted 6 months after treatment discontinuation. Targeting specifically the protein kinase DYRK1A that is overexpressed in DS and inhibited by EGCG could lead to treatment of cognitive deficits in DS.

“A phase 3 clinical trial in young adults, safety and efficacy trials in children as well as determination of long term effects of EGCG exposure will need to be elucidated before this treatment is proposed to people with DS, although as a nutraceutical, it is already being “self-prescribed” by caregivers. This increases the urgency for adequate funding to answer remaining questions about potential harm as well as an objective determination of efficacy. Meanwhile, other important clinical trials in individuals with DS [1] will bring more information on how, at what ages and for how long pharmaceutical treatments might ameliorate cognitive impairments from birth and throughout life in people with DS.

“We cannot recommend that people self-medicate with green tea because different varieties contain different levels of the key compound. It’s also vital that we see the results of a toxicity study with these nutraceuticals before going further.”

[1] CLEMATIS: NCT02024789 on NIH Clinical Trials register

Prof. Roger Reeves, Professor of Genetics, Johns Hopkins University and McKusick-Nathans Institute for Genetic Medicine, Baltimore, USA and President of the T21 Research Society, said:

“The authors of the TESDAD study conclude that targeting specifically the protein kinase DYRK1A that is overexpressed in Down Syndrome (DS) and inhibited by epigallocatechin-3-gallate (EGCG) could lead to treatment of cognitive deficits in DS. However, few inhibitors show a high degree of specificity for only a single kinase. While EGCG has been demonstrated to inhibit the activity of DYRK1A in a number of published reports, assessment of EGCG effects on 28 kinases identified a second target, PRAK, as equally inhibited and three other kinases, ERK2, 3-phosphoinositidedependent protein kinase 1, and Rho-dependent protein kinase II as somewhat inhibited; a single concentration of EGCG was used in these experiments [2]. Combined with variability in actual EGCG levels in commercial preparations of green tea extract [3], it is important that the public be aware of limitations in current knowledge about potential effects and side-effects of unsupervised use of EGCG ‘treatment.’”

[2] Abeysekera, I., Thomas, J., Georgiadis, T.M., Berman, A.G., Hammond, M.A., Dria, K.J., Wallace, J.M., and Roper, R.J. (2016). Differential effects of Epigallocatechin-3-gallate containing supplements on correcting skeletal defects in a Down syndrome mouse model. Mol Nutr Food Res 60, 717-726.

[3] Bain, J., McLauchlan, H., Elliott, M., and Cohen, P. (2003). The specificities of protein kinase inhibitors: an update. Biochem J 371, 199-204.

‘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’ by de la Torre et al. published in The Lancet Neurology on Monday 6^th June. 

Declared interests

Prof. Nutt: “I have promoted the use of GABA inverse agonists in Down syndrome.”

Dr Potier: “I have grants from pharma industries (Servier, Roche and Pfizer) on Alzheimer’s disease, not on Down syndrome.”

Prof. Reeves: None received