Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-cjp7w Total loading time: 0 Render date: 2024-06-23T19:13:45.430Z Has data issue: false hasContentIssue false

17 - Perspectives of hybrid therapeutic strategies in intellectual disabilities and Down syndrome

Published online by Cambridge University Press:  05 July 2011

Jean-Adolphe Rondal
Affiliation:
Pontifical Salesian University
Juan Perera
Affiliation:
University of the Balearic Islands
Jean-Adolphe Rondal
Affiliation:
Université de Liège, Belgium
Juan Perera
Affiliation:
Universitat de les Illes Balears, Palma de Mallorca
Donna Spiker
Affiliation:
Stanford Research Institute International
Get access

Summary

Major progress in molecular genetics over the last decades has made it possible to chart a number of mammalian genotypes including the human one composed of approximately 23,000 genes distributed over 23 pairs of chromosomes. Although the particular locations of these genes are known, their exact roles in cell functioning have not been specified yet except for a few hundred. However, the available knowledge is sufficient to support the definition of animal analogs to some conditions leading to intellectual disabilities in humans, such as fragile-X (etiologically linked to a mutation of the gene FMR-1 or FMR-2 on chromosome X) and Down syndrome (DS) (trisomy 21). For example, trisomy 21 in humans is mimicked (genotypically and phenotypically) in mice by experimentally induced trisomy 16. Recent work suggests that it is possible to ameliorate, at least partially, FMR-1 knockout (KO) mice, an animal model of fragile-X syndrome (FXS), at both cellular and behavioral levels in inhibiting the catalytic activity of p21-activated kinase (PAK), a kinase known to play a critical role in actin polymerization and dendritic spine morphogenesis (Hayashi et al., 2007). Greater spine density and elongated spines in the cortex, morphological synaptic abnormalities commonly observed in FXS, are partly restored by postnatal expression of a dominant negative PAK transgene in the forebrain. Likewise, the deficit in cortical long-term potentiation observed in FMR-1 KO mice is fully restored by the PAK transgene.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bailey, D., Bruer, J., Symons, F., Lichtman, J. (2001). Critical Thinking about Critical Periods. Baltimore: Brookes.Google Scholar
Baxter, L., Moran, T., Richtmeier, J., Troncoso, J., Reeves, R. (2000). Discovery and genetic localization of Down syndrome cerebellar phenotype using the Ts65Dn mouse. Human Molecular Genetics, 9, 195–202.CrossRefGoogle ScholarPubMed
Davisson, M., Schmidt, C., Akeson, E. (1990). Segmental trisomy of murine chromosome16: a new model system for studying Down syndrome. Progress in Clinical Biological Research, 360, 263–280.Google Scholar
Delabar, J. (2007). Perspective on gene-based therapies. In Rondal, J. A. & Quartino, A. Rasore (eds.), Therapies and Rehabilitation in Down Syndrome, pp. 1–17. Chichester: Wiley.Google Scholar
Epstein, C. (1999). The future of biological research on Down syndrome. In Rondal, J. A., Perera, J., Nadel, L. (eds.), Down Syndrome. A Review of Current Knowledge, pp. 210–222. London: Whurr.Google Scholar
Hattori, M., Fujiyama, A., Taylor, D., et al. (2000). The DNA sequence of human chromosome 21. Nature, 405, 311–319.CrossRefGoogle ScholarPubMed
Hayashi, M., Rao, S., Seo, J., et al. (2007). Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proceedings of the National Academy of Sciences of the United States of America, 104(27), 11489–11494.CrossRefGoogle ScholarPubMed
Jenkins, E. & Velinov, M. (2001). Down syndrome and the human genome. Down Syndrome Quarterly, 6, 1–12.Google Scholar
Korenberg, J., Aaltonen, J., Brahe, C., et al. (1997). Report and abstracts of the 6th International Workshop on Human Chromosome 21 Mapping 1996. Cold Spring Harbor, New York, USA. May 6–8, 1996. Cytogenetic Cell Genetics, 79(1–2), 21–52.Google Scholar
Peterson, A., Patil, N., Robins, C., et al. (1994). A transcript map of the Down syndrome critical region of chromosome 21. Human Molecular Genetics, 3, 1735–1742.CrossRefGoogle ScholarPubMed
Pritchard, M. & Kola, I. (2007). The biological bases of pharmacological therapies in Down syndrome. In Rondal, J. A. & Quartino, A. Rasore (eds.), Therapies and Rehabilitation in Down Syndrome, pp. 18– 27. Chichester: Wiley.Google Scholar
Reiss, D. & Niederhiser, J. (2000). The interplay of genetic influences and social processes in developmental theory: specific mechanisms are coming into view. Development and Psychopathology, 12, 357–374.CrossRefGoogle ScholarPubMed
Rutter, M. (2002). Nature, nurture, and development: from evangelism through science toward policy and practice. Child Development, 73, 1–21.CrossRefGoogle ScholarPubMed
Sago, H., Carlson, E., Smith, D., et al. (1998). Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proceedings of the National Academy of Sciences of the United States of America, 95 (14), 6256–6261.CrossRefGoogle ScholarPubMed
Seppa, N. (2000). Bubble babies thrive on gene therapy. Science News Online (retrieved from www.science online.org).CrossRef
Warren, S. (2002). Presidential address 2002 – Genes, brains, and behavior: the road ahead. Mental Retardation, 40(6), 471–476.2.0.CO;2>CrossRefGoogle ScholarPubMed
Wenner, M. (2008). Regaining lost luster. New developments and clinical trials breathe life back into gene therapy. Scientific American, January, 9–10.CrossRef
Wisniewski, K., Kida, E., Golabeck, A., et al. (2006). Down syndrome: from pathology to pathogenesis. In Rondal, J. A. & Perera, J. (eds.), Down Syndrome. Neurobehavioural Specificity, pp. 17–33. Chichester: Wiley.Google Scholar
Ye, X., Mitchell, M., Newman, K., Batshaw, M. (2001). Prospects for prenatal gene therapy in disorders causing mental retardation. Mental Retardation and Developmental Disabilities Research Review, 7, 65–72.3.0.CO;2-9>CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×