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Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG, Jaeschke G, Bear MF, Lindemann L. Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice. Neuron. 2012 Apr 12 ; 74(1):49-56. Pubmed Abstract

Comments on News and Primary Papers
Comment by:  Bernard Crespi
Submitted 20 April 2012
Posted 25 April 2012
  I recommend the Primary Papers

The emerging possibility of reversing neurodevelopmental disorders in children or adults (Ehninger et al., 2008) represents one of the most exciting recent developments in psychiatry.

With regard to effects from modulation of the mGlur5 receptor, of notable interest to schizophrenia researchers might be the suite of recent studies focused on the development of positive allosteric modulators of this receptor for schizophrenia treatment (e.g., Rodriguez et al., 2010; Spear et al., 2011; Gray et al., 2012). Agonists of mGlur5 now have demonstrated efficacy in rodent models of schizophrenia, and await testing in humans.

Michalon et al. (2012), of course, demonstrated strong positive effects of mGlur5 antagonists in ameliorating an animal model of Fragile X syndrome, an autism spectrum condition. These contrasting results of mGlur5 antagonists for an autism spectrum condition and agonists of the same receptor for treating schizophrenia suggest that comparative pharmacological approaches may be useful in conceptualizing new treatment approaches for both sets of neurodevelopmental conditions—and perhaps, leading to new ways of reversing them.

References:

Ehninger D, Li W, Fox K, Stryker MP, Silva AJ. Reversing neurodevelopmental disorders in adults. Neuron . 2008 Dec 26 ; 60(6):950-60. Abstract

Gray LJ, Hannan AJ, Zhang X. Metabotropic glutamate receptors as targets for novel antipsychotic treatments. Curr Pharm Biotechnol. 2012 Jan 26. Abstract

Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG, Jaeschke G, Bear MF, Lindemann L. Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice. Neuron. 12 April 2012;74:49-56. Abstract

Rodriguez AL, Grier MD, Jones CK, Herman EJ, Kane AS, Smith RL, Williams R, Zhou Y, Marlo JE, Days EL, Blatt TN, Jadhav S, Menon UN, Vinson PN, Rook JM, Stauffer SR, Niswender CM, Lindsley CW, Weaver CD, Conn PJ. Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol Pharmacol. 2010 Dec;78(6):1105-23. Abstract

Spear N, Gadient RA, Wilkins DE, Do M, Smith JS, Zeller KL, Schroeder P, Zhang M, Arora J, Chhajlani V. Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator. Eur J Pharmacol. 2011 Jun 1;659(2-3):146-54. Abstract

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