title: Prenatal treatment of Down syndrome: a reality?
abstract: OBJECTIVE
  Down syndrome affects more than 5 million people globally. During the last 10 years, there has been a dramatic increase in the research efforts focused on therapeutic interventions to improve learning and memory in Down syndrome.
  
  
  RESULTS
  This review summarizes the different functional abnormalities targeted by researchers in mouse models of Down syndrome. Three main strategies have been used: neural stem cell implantation; environmental enrichment and physical exercise; and pharmacotherapy. Pharmacological targets include the choline pathway, GABA and NMDA receptors, DYRK1A protein, oxidative stress and pathways involved in development and neurogenesis. Many strategies have improved learning and memory as well as electrophysiological and molecular alterations in affected animals. To date, eight molecules have been tested in human adult clinical trials. No studies have yet been performed on infants. However, compelling studies reveal that permanent brain alterations originate during fetal life in Down syndrome. Early prenatal diagnosis offers a 28 weeks window to positively impact brain development and improve postnatal cognitive outcome in affected individuals. Only a few approaches (Epigallocatechine gallate, NAP/SAL, fluoxetine, and apigenin) have been used to treat mice in utero; these showed therapeutic effects that persisted to adulthood.
  
  
  CONCLUSIONS
  In this article, we discuss the challenges, recent progress, and lessons learned that pave the way for new therapeutic approaches in Down syndrome.
authors.affiliation: aMother Infant Research Institute, Tufts Medical Center and the Floating Hospital for Children, Boston, Massachusetts, USA bUniv Paris Diderot, Sorbonne Paris Cité, CNRS UMR 8251, Adaptive Functional Biology, Paris, France.
authors.forename: Fayçal
authors.initials: F
authors.lastname: Guedj
authors.forename: Diana W
authors.initials: DW
authors.lastname: Bianchi
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Delabar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D047310:Apigenin / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D058953:Neural Stem Cells; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods / Q000639:trends; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D033581:Stem Cell Transplantation; D000097603:Dyrk Kinases
chemical_list: D047310:Apigenin; D002392:Catechin; D002794:Choline; D005473:Fluoxetine; D018696:Neuroprotective Agents; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D000097603:Dyrk Kinases; C045651:epigallocatechin gallate