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Avigen AV411 as a glia modulator in neuropathic pain

AV411 is orally bioavailable small molecule, which is characterized as a glial attenuator, that suppresses pro-inflammatory cytokines IL-1 beta, TNF alpha, and IL-6, and may upregulate the anti-inflammatory cytokine IL-10. It is under devellopment by Avigen, Inc. (Nasdaq:AVGN), a biopharmaceutical company developing innovative therapies for the treatment of neurological conditions.

The drug was first approved in Japan around 1992. ^[1] The drug has been prescribed to over a million patients and has a good post-marketing safety profile in nearly 15,000 patients dosed at the prescribed doses.

AV411 or ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma in Japan. It has been used for other indications too and it acts as a nonselective inhibitor of various phosphodiesterases (PDEs) resulting in antiinflammatory activity.

The PDE inhibitor AV411 inhibits the catalytic and chemotactic functions of the proinflammatory protein, macrophage migration inhibitory factor (MIF). It seems to be a noncompetitive inhibitors of the p-hydroxyphenylpyruvate (HPP) tautomerase activity of MIF ^[2]

Additional information on AV411 can be found on Avigen's website at http://www.avigen.com. Read more: http://www.drugs.com/clinical_trials/avigen-s-av411-highlighted-special-issue-neuron-glia-biology-213.html#ixzz12zxB9z3J

Prof. dr. Jan M. Keppel Hesselink MD, PhD, october 2010

Referenties

[1]: Nishino K, Ohkubo H, Ohashi M, Hara S, Kito J, Irikura T. | KC-404: a potential anti-allergic agent with antagonistic action against slow reacting substance of anaphylaxis. | Jpn J Pharmacol. | 1983 Apr;33(2):267-78.

[2]: Cho Y, Crichlow GV, Vermeire JJ, Leng L, Du X, Hodsdon ME, Bucala R, Cappello M, Gross M, Gaeta F, Johnson K, Lolis EJ. | Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast. | Proc Natl Acad Sci U S A. | 2010 Jun 22;107(25):11313-8. Epub 2010 Jun 8.