Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Community Corner
  • Published:

Trialing targeted therapies for autism

Nature Medicine volume 18, pages 1746–1747 (2012)Cite this article

Subjects

Lu Chen, Allan L Reiss & Thomas C Südhof

FXS, a monogenic form of intellectual disability associated with developmental impairments, may be the first genetic neuropsychiatric disorder to be treated pharmacologically from a disease-specific perspective. Great excitement surrounds the pioneering work of Mark Bear's laboratory, which indicated that responses mediated by metabotropic glutamate receptor 5 (mGluR5) are upregulated in FXS, suggesting that mGluR5 inhibition may be clinically beneficial3. Despite promising mouse studies, however, the initial clinical trials with mGluR5 inhibitors showed limited success4, prompting the search for alternative avenues. Two recent papers from the same groups explored the possibility that activation of GABAB receptors as a counterpoint to increased mGluR5 activity may be beneficial1,2. Again, the mouse model studies were encouraging, but the clinical study results were not as promising. In treated patients, primary endpoint measures were not significantly changed. Only post hoc secondary measures with indeterminate relevance to the clinical phenotype were improved.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Henderson, C. et al. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Sci. Transl. Med. 4, 152ra128 (2012).

    Article  Google Scholar 

  2. Berry-Kravis, E.M. et al. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci. Transl. Med. 4, 152ra127 (2012).

    Article  Google Scholar 

  3. Krueger, D.D. & Bear, M.F. Toward fulfilling the promise of molecular medicine in fragile X syndrome. Annu. Rev. Med. 62, 411–429 (2011).

    Article  CAS  Google Scholar 

  4. Jacquemont, S. et al. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci. Transl. Med. 3, 64ra61 (2011).

    Article  Google Scholar 

  5. Soden, M.E. & Chen, L. Fragile X protein FMRP is required for homeostatic plasticity and regulation of synaptic strength by retinoic acid. J. Neurosci. 30, 16910–16921 (2010).

    Article  CAS  Google Scholar 

  6. Hall, S.S., Hammond, J.L., Hirt, M. & Reiss, A.L. A. 'learning platform' approach to outcome measurement in fragile X syndrome: a preliminary psychometric study. J. Intellect. Disabil. Res. 56, 947–960 (2012).

    Article  CAS  Google Scholar 

  7. Guy, J., Gan, J., Selfridge, J., Cobb, S. & Bird, A. Reversal of neurological defects in a mouse model of Rett syndrome. Science 23, 1143–1147 (2007).

    Article  Google Scholar 

  8. Bear, M.F., Huber, K.M. & Warren, S.T. The mGluR theory of fragile X mental retardation. Trends in Neurosci. 27, 370–377 (2004).

    Article  CAS  Google Scholar 

  9. Katz, D.M., et al. Preclinical research in Rett syndrome: setting the foundation for translational success. Dis. Model Mech. 5, 733–745 (2012).

    Article  CAS  Google Scholar 

  10. Ecker, C., Spooren, W. & Murphy, D.G. Translational approaches to the biology of Autism: false dawn or a new era? Mol. Psychiatry published online, 10.1038/mp.2012.102 (17 July 2012).

  11. Mendez, M.A. et al. The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: a pilot [(11)C]Ro15–4513 positron emission tomography study. Neuropharmacology published online, 10.1016/j.neuropharm.2012.04.008 (21 April 2012).

  12. Ecker, C. et al. Describing the brain in autism in five dimensions–magnetic resonance imaging-assisted diagnosis of autism spectrum disorder using a multiparameter classification approach. J. Neurosci. 30, 10612–10623 (2010).

    Article  CAS  Google Scholar 

Download references

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trialing targeted therapies for autism. Nat Med 18, 1746–1747 (2012). https://doi.org/10.1038/nm.3027

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.3027

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing