Download: Prof. Jacqueline London "Therapeutical Approach for Trisomy 21 & Alzheimer disease



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The Search for Medicine for Down's Syndrome
Towards an International Research Alliance

September 17th 2011

The Wellcome Trust Conference Centre
Genome Campus
Hinxton, Cambridge, UK.

Program sponsored by
The Down's Syndrome Research Foundation UK
and a grant from Alzheimer's Research UK:

Jacqueline London professor at the Paris-Diderot university. She founded 21 years ago a French Association for Research on Trisomy 21 (AFRT) with a publication "News from chromosome 21". She is a Board member of European Down's Syndrome Association (EDSA). Her research is devoted to mouse models for Down syndrome especially in relation to oxidative stress, homocystein metabolism, aging and some side characteristics of persons with trisomy 21 (skin, hair and sleep manifestations).

Therapeutical Approach for Common clinical aspects in Trisomy 21 and Alzheimer disease University Denis-Diderot,35 rue Hélène Brion, 75205 Paris Cedex 13, France
Although it is well reported that patients with Down syndrome (DS) are at high risk to develop the Alzheimer's type dementia by 50 years, it is known that not all of them will develop the dementia and very few drugs used for Alzheimer patients have been evaluated in adults with Down syndrome to prevent dementia.These drugs have been or will be evaluated to treat the cognitive impairment in children or young adults with DS and so far there are only some pilot studies (memantine, PTZ, L-DOPS, folinic acid) but in this meeting we may have new good results especially for memantine and donepezil. It is generally difficult to evaluate with good accuracy the cognitive and behavioral improvement after drug or placebo administration in persons with DS regarding the great variablity between them, the effect of stress on their behaviour and the various psychological batteries of tests used for validation and to have reliable controls matched either by age or by IQ. We thus proposed that in addition to use a battery of tests for the cognitive improvement, it will be valuable to test other paradigms which are affected in persons either with early Alzheimer or with Down syndrome. For instance some early signs present in Alzheimer disease patients are also present in young persons with Down syndrome, signs which some of them can be improved by early intervention but could much better also be improved with pharmacological treatment. Among these early signs of AD and also present in DS are poor: smelling (which is easily evaluated), sleep pertubations (which affect 80% of the persons with DS), poor orientation, agraphia and in some cases aphasia. It might be also valuable to correlate these signs with biochemical parameters such as lipid metabolism, APP metabolism (production of Abeta40, Abeta42 and saAPP), cholesterol and insulin metabolism (a recent paper show that intranasal insulin improves cognitive impairment), methylation status and when it is possible the metabolism of catecholamines and serotonin.
We thus suggest to reinforce the studies of the present (folinic acid, memantine, PTZ, EGCG) or coming potential drugs on sleep and smelling properties which might be, in persons with trisomy 21, more easily evaluated than cognitive improvements. In that regard, in Dr. Jean Delabar laboratory in Paris, we have studied sleep properties in DYRK1A mice treated with EGCG or placebo. We have also evaluated the effect of DYRK1A or/and APP overexpression on catecholamines and serotonine production and catabolism in various brain areas.
Preliminary results show that EGCG might be a good treatment for sleep abnormalities related to cognitive impairments.