A Curative Perspective on Down Syndrome

Authors

  • Jean A. Rondal University of Liège, Department of Cognitive Sciences, Building 32, Sart Tilman, Liège 4000, Belgium

DOI:

https://doi.org/10.6000/2292-2598.2019.07.03.3

Keywords:

Aneuploidies, Down syndrome, genetic therapy, cognitive pharmacotherapy, Alzheimer disease.

Abstract

A curative perspective on Down syndrome is pointing out. Experimental work regarding chromosome correction and corrective action on genes and proteins is yielding positive results. They open the way to advances in dealing with aneuploidies and may end up markedly changing the life of the individuals affected with these conditions at the same time, several molecules are in the research pipeline of cognitive pharmacotherapy. The paper summarizes these advances and set them into perspective for the future of Down syndrome. Research on the effects of the amyloid cascade in the etiology of Alzheimer disease, which is more frequent in aging persons with Down syndrome, is also analyzed. Its potential for improving early diagnosis and paving the way for stabilizing the condition at least in the first stages is also discussed.

References

Rondal JA. Le futur de la trisomie 21. Une perspective curative. Brussels: Mardaga 2019.

Li L, Chang K, Wang P, Hirata R, Papayannopoulou T, Russell D. Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell 2012; 11: 615-9. https://doi.org/10.1016/j.stem.2012.08.004

Jiang J, Jing Y, Cost G, Chiang JC, Kolpa H, Cotton A, Carone D, Carone B, Shivak D, Guschin D, Pearl E, Rebar E, Byron M, Gregory P, Brown C, Urnov F, Hall L, Lawrence J. Translating dosage compensation for trisomy 21. Nature 2013; 500: 296-300. https://doi.org/10.1038/nature12394

Lee J, Davidow L, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 1999; 21: 400-4. https://doi.org/10.1038/7734

Amano T, Jeffries E, Amano M, Ko A, Yu H, Ko M. Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures. DNA Res 2015; 22: 331-42. https://doi.org/10.1093/dnares/dsv016

Wang X, Zhao Y, Zhang X, Badie H, Zhou Y, Mu Y, Loo L, Cai L, Thompson R, Yang , Chen Y, Johnson P, Wu C, Bu G, Mobley W, Zhang , Gage F, Ranscht B, Zhang Y, Lipton S, Hong W, Xu H. Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down’s syndrome. Nat Med 2013; 19: 473-80. https://doi.org/10.1038/nm.3117

Rueda N, Flórez J, Martinez-Cue C. Mouse models of Down syndrome as a tool to unravel the causes of mental disabilities. Neural Plasticity 2012. https://doi.org/10.1155/2012/584071

Fillat C, Bofill-De Ros X, Santos M, Martin E, Andreu N, Villanueva E, D’Amico D, Dierssen M, Altafaj X. Identification de genes clave implicados en el sindrome de Down mediante terapia genetica. Rev Med Int Sindrome Down 2014; 18(2): 21-8. https://doi.org/10.1016/S2171-9748(14)70049-2

Caplan A, Wilson J. The clinical challenges of in utero therapy. Nat Genet 2000; 24: 107-8. https://doi.org/10.1038/72747

Guedj F, Sebrie C, Rivals I, Ledru A, Paly E, Bizot J, Smith D, Rubin E, Gillet B, Arbones M, Delabar, JM. Green tea polyphenols rescue brain defects induced by overexpression of DYRK1A. Plos ONE 2009; 4(2): 1-8. https://doi.org/10.1371/journal.pone.0004606

Stagni F, Giacomini A, Emili M, Trazzi S, Guidi S, Sassi M, Ciani E, Rimondini R, Bartesaghi R. Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome. Neuroscience 2016; 333: 277-301. https://doi.org/10.1016/j.neuroscience.2016.07.031

De la Torre R, de Sola S, Pons M, Duchon A, De Lagran M, Farre M, Fito M, Benejan B, Langohr K, Rodriguez J, Pujadas M, Bizot J, Cuenca A, Janel N, Catuara S, Covas M, Bléhaut H, Hérault Y, Delabar JM, Dierssen M. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in human. Mol Nutr Food Res 2014; 58: 278-88. https://doi.org/10.1002/mnfr.201300325

Sparks A, Truble C, Wang E, Song K, Oliphant A. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: Evaluation for trisomy 21 and trisomy 18. Am J Obst Gynecol 2012; 206: 319.e1- e9. https://doi.org/10.1016/j.ajog.2012.01.030

Nicolaides K, Syngelaki A, Poon L, Gil M, Wright D. First-trimester contingent screening for trisomy 21, 18, and 13 by biomarkers and maternal blood cell-free DNA testing. Fetal Diagn Ther 2014; 35: 185-92. https://doi.org/10.1159/000356066

Guidi S, Stagni F, Bianchi P, Ciani E, Giacomini A, De Franceschi M, Moldrich R, Kurniawan N, Mardon K, Giuliani A, Calza L, Bartesaghi R. Prenatal pharmacotherapy rescues brain development in a Down’s syndrome mouse model. Brain 2014; 137: 380-401. https://doi.org/10.1093/brain/awt340

Kishnani P, Sommer B, Handen B, Seltzer B, Capone G, Spiridigliozzi G, Heller J, Richardson S, McRae T. The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome. Am J Med Genet 2009; 149: 1641-54. https://doi.org/10.1002/ajmg.a.32953

Capone G. Pharmacotherapy for children with Down syndrome. In Rondal JA, Perera J, Spiker D, editors. Neurocognitive rehabilitation of Down syndrome. The early years. Cambridge, United Kingdom: Cambridge University Press 2011; pp. 96-116. https://doi.org/10.1017/CBO9780511919299.008

Kishnani P, Heller J, Spiridigliozzi G, Lott I, Escobar L, Richardson S, Zhang R, McRae T. Donepezil for treatment of cognitive dysfunction in children with Down syndrome aged 10-17. Am J Med Genet 2010; 152: 3028-35. https://doi.org/10.1002/ajmg.a.33730

Heller J, Spiridigliozzi G, Crissman B, Sullivan J, Eells R, Li J, Doraiswamy P, Krishnan R, Kishnani P. Safety and efficacy of rivastigmine in adolescents with Down syndrome: A preliminary 20-week, open-label study. J Child Adolesc Psychopharmacol 2006; 16: 755-65. https://doi.org/10.1089/cap.2006.16.755

Heller J, Spiridigliozzi G, Kishnani P, Crissman B, McKillop J, Yamamoto H. Safety and efficacy of rivastigmine in adolescents with Down syndrome: Long-term follow-up. J Child Adolesc Psychopharmacol 2010; 20: 517-20. https://doi.org/10.1089/cap.2009.0099

Lobaugh N, Karaskov V, Rombough V, Rovet J, Bryson S, Greenbaum R, Haslam R, Koren G. Piracetam therapy does not enhance cognitive functioning in children with Down syndrome. Arch Pediatr Adolesc Med 2001; 15: 442-8. https://doi.org/10.1001/archpedi.155.4.442

Chen C, Jiang P, Xue H, Peterson S, Tran H, McCann A, Parast M, Li S, Pleasure D, Laurent L, Loring J, Liu Y, Deng W. Role of astroglia in Down’s syndrome revealed by patient-derived human-induced pluripotent stem cells. Nat Com 2014. https://doi.org/10.1038/ncomms5430

Patterson D Development of the brain and metabolism. In Rondal JA, Perera J, Spiker D, editors. Neurocognitive rehabilitation of Down syndrome. The early years. Cambridge, United Kingdom: Cambridge University Press 2011; pp. 85-95. https://doi.org/10.1017/CBO9780511919299.007

Firth N. Startin C, Fisher E, Nizetic D, Kong Chian L, Hardy J, Tybulewics A, Karmiloff-Smith A, Strydom A. Aging related cognitive changes associated with Alzheimer’s disease in Down syndrome. Ann Clin Trans Neurol 2018; 20: 741-51. https://doi.org/10.1002/acn3.571

Rogaeva E, Meng Y, Lee J, Gu Y, Kawarai T, Zou F. The neuronal sortilin-related receptor SORT1 is genetically associated with Alzheimer’s disease. Nat Genet 2007; 39: 168-77. https://doi.org/10.1038/ng1943

Hochino T, Kamino K, Matsumoto M. Gene dose effect of the APOE-epsilon 4 allele on plasma HDL cholesterol level in patients with Alzheimer’s disease. Neurobiol Aging 2002; 2: 41-5. https://doi.org/10.1016/S0197-4580(01)00252-4

Sanchez M, Heyn S, Das D, Moghadam S, Martin K, Salehi A. Neurobiological elements of cognitive dysfunction in Down syndrome: Exploring the role of APP. Biol Psychiatry 2012; 71: 403-9. https://doi.org/10.1016/j.biopsych.2011.08.016

Pritchard M, Kola I. The biological bases of pharmacological therapies in Down syndrome. In Rondal JA, Rasore Quartino A., editors. Therapies and rehabilitation in Down syndrome. Chichester, United Kingdom: Wiley 2007; pp. 18-27.

Boada R, Hutaff-Lee C, Schrader A, Weitzenkamp D, Benke T, Goldson E, Costa A. Antagonism of NMDA receptors as a potential treatment for Down syndrome: A pilot randomized controlled trial. Transl Psychiatry 2012; 2e141. https://doi.org/10.1038/tp.2012.66

Matsunaga S, Kishi T, Annes P, Basun H, Hampel H, Iwata N. Lithium as a treatment for Alzheiner’s disease: A systematic review and meta-analysis. J Alzheimer Dis 2015; 48: 403-10. https://doi.org/10.3233/JAD-150437

Rasore Quartino, A. Le terapie attuali per le persone con sindrome di Down: La stato del arte. In Rasore Quartino A, Baccichetti C, editors. Il presente incontra il futuro. La sindrome di Down oggi e domani. Pieve di Cadore, Italy: Tiziano Edizioni 2012; pp. 53-80.

Garcia-Cerro S, Rueda N, Vidal V, Lantigua S, Martinez-Cue C. Normalizing the gene dosage of DYRK1A in a mouse model of Down syndrome rescues several Alzheimer’s disease phenotypes. Neurobiol Dis 2017; 106: 76-88. https://doi.org/10.1016/j.nbd.2017.06.010

Kawakubo T, Mori R, Shirotani N, Iwata N, Asai M. Neprilysin is suppressed by dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) in Down syndrome derived fibroblasts. Biol Pharm Bull 2017; 40: 327-33. https://doi.org/10.1248/bpb.b16-00825

Lee N, Chien Y, Hwu W. A review of biomarkers for Alzheimer’s disease in Down syndrome. Neurol Ther 2017; 6: 69-81. https://doi.org/10.1007/s40120-017-0071-y

Hartley S, Handen B, Devenny D, Mihaila I, Hardison R, Lao P, Klunk W, Bulova P, Johnson S, Christian B. Cognitive decline and brain amyloid-beta accumulation across 3 years in adults with Down syndrome. Neurobiol Aging 2017; 58: 68-76. https://doi.org/10.1016/j.neurobiolaging.2017.05.019

Motta C, Di Lorenzo F, Ponzo V, Pellicciari M, Bonni S, Picazio S, Biagio Mercuri N, Caltagirone C, Martorana A, Koch G. Transcranial magnetic stimulation predicts cognitive decline in patients with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2018; 0: 1-6; published online: DOI 10.1136/jnnp-2017-317879.

Kevles D. In the name of eugenics. Cambridge, Massachusetts: Harvard University Press 1999.

Downloads

Published

2019-08-06

How to Cite

Rondal, J. A. (2019). A Curative Perspective on Down Syndrome. Journal of Intellectual Disability - Diagnosis and Treatment, 7(3), 77–85. https://doi.org/10.6000/2292-2598.2019.07.03.3

Issue

Section

General Articles