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Effect of the Aβ Aggregation Modulator MRZ-99030 on Retinal Damage in an Animal Model of Glaucoma

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Abstract

Several lines of evidence suggest that there are similarities in the pathomechanisms of glaucoma and Alzheimer’s disease, and that amyloid-beta (Aβ) could be a new, promising target for neuroprotective therapy of glaucoma. In the present study, we evaluated the effect of the Aβ aggregation modulator MRZ-99030 in the Morrison model of glaucoma based on increased intraocular pressure (IOP) in rats. MRZ-99030 provided dose-dependent neuroprotection and at the highest dose (240 mg/kg) reduced the degree of RGC apoptosis to 33 % of that seen after vehicle (P < 0.05; one-way ANOVA). No significant effect on IOP was observed. Pharmacokinetic experiments showed that following systemic injection of MRZ-99030, concentrations above affinity for Aβ were reached. Hence the present results are consistent with the notion that Aβ is a promising target for neuroprotective intervention in glaucoma and that MRZ-99030 may be a good drug candidate for further development.

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Acknowledgments

We wish to thank Prof. Ehud Gazit from Tel Aviv University for first bringing our attention to this dipeptide ((R)-(2-[2-Amino-3-(1H-indol-3-yl)-propionylamino]-2-methyl-propionic acid) that was first synthesized/characterized in his laboratories and for his continuous intellectual support in our preclinical studies.

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Authors and Affiliations

  1. Visual Neuroscience, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK

    T. E. Salt, S. Nizari & M. F. Cordeiro

  2. Merz Pharmaceuticals GmbH, Alfred Wegener Strasse 2, 60438, Frankfurt/Main, Germany

    H. Russ & W. Danysz

Authors
  1. T. E. Salt
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  2. S. Nizari
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  3. M. F. Cordeiro
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  4. H. Russ
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  5. W. Danysz
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Correspondence to W. Danysz.

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Salt, T.E., Nizari, S., Cordeiro, M.F. et al. Effect of the Aβ Aggregation Modulator MRZ-99030 on Retinal Damage in an Animal Model of Glaucoma. Neurotox Res 26, 440–446 (2014). https://doi.org/10.1007/s12640-014-9488-6

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  • DOI: https://doi.org/10.1007/s12640-014-9488-6

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