July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Sustained neuroprotective effect of novel Aβ aggregation modulator GAL-101 shown in dry AMD and glaucoma models with transient peak concentrations using eye drops
Author Affiliations & Notes
  • Hermann Russ
    Science, Galimedix Therapeutics, Altendorf, Schwyz, Switzerland
  • Christopher Parsons
    Science, Galimedix Therapeutics, Altendorf, Schwyz, Switzerland
  • Yaniv Barkana
    Science, Galimedix Therapeutics, Altendorf, Schwyz, Switzerland
  • Andrew L. Pearlman
    Management, Galimedix Therapeutics Inc., Israel
  • Jeffrey S. Heier
    Ophthalmology, Ophthalmic Consultants of Boston, Boston, Massachusetts, United States
  • Leonard A Levin
    Montreal Neurological Insitute and Hospital, Montreal, Quebec, Canada
  • Robert N Weinreb
    Department of Ophthalmology, Shiley Eye Institute, La Jolla, California, United States
  • Jeffrey M Liebmann
    Department of Ophthalmology, Columbia University Medical Center, New York City, New York, United States
  • Footnotes
    Commercial Relationships   Hermann Russ, Galimedix Therapeutics Inc. (E); Christopher Parsons, Galimedix Therapeutics Inc. (E); Yaniv Barkana, Galimedix Therapeutika Inc. (E); Andrew Pearlman, Galimedix Therapeutics Inc. (E); Jeffrey S. Heier, Galimedix (C); Leonard Levin, Aerie (C), Eyevensys (C), Galimedix (C), Quark (C), Regenera (C); Robert Weinreb, Galimedix (C); Jeffrey Liebmann, Galimedix Therapeutics (S)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5393. doi:
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      Hermann Russ, Christopher Parsons, Yaniv Barkana, Andrew L. Pearlman, Jeffrey S. Heier, Leonard A Levin, Robert N Weinreb, Jeffrey M Liebmann; Sustained neuroprotective effect of novel Aβ aggregation modulator GAL-101 shown in dry AMD and glaucoma models with transient peak concentrations using eye drops. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5393.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Published research on the role of toxic soluble oligomers of misfolded β-amyloid (Aβ) in neurodegenerative disease grows dramatically. These oligomers are increasingly becoming recognized as potential causes of synaptic dysfunction and neurodegeneration in Alzheimer disease, glaucoma and dry age-related macular degeneration (AMD). GAL-101 (formerly MRZ-99030), a novel small molecule, selectively clears misfolded Aβ from neural tissues to prevent formation of neurotoxic Aβ oligomers and their consequent neurotoxicity. We explored MOA and neuroprotective effect of GAL-101 via topical administration in animal models of glaucoma and dry AMD. These experiments led us to hypothesize that peak delivery from a single administration might provide sustained therapeutic effects.

Methods : Topical delivery was tested in cynomolgus monkeys. Neuroprotection was tested in glaucoma rat model with 6 weeks elevated IOP, effect on Aβ deposits tested in 6 months CFH-/-and in 24 months old C57/6 mice with extensive Aβ deposits. Aβ toxicity was tested on hippocampal slices in vitromeasured via LTP.

Results : GAL-101 affinity to Aβ measured by SPR is 30 nanomolar (nM), and showed rapid formation of amorphous, non-toxic aggregates of Aβ (”blobs”) seen on AFM. Single eyedrops in monkeys sustained GAL-101 concentrations >100 nM in the retina for >2 hours, via the sclera and choroid. RGC death in rats was 20% after 6 weeks IOP elevation, but <1% with daily GAL-101 eye drops (>90% neuroprotection), with similar results from single administration of GAL-101 via intravitreal or subcutaneous injection prior to IOP elevation. GAL-101 eye drops given in AMD mice the first 3 of each 30 days resulted in 40-60% less toxic Aβ deposits vs placebo after 90 days. 50 nM Aβ was toxic to hippocampal cells but was neutralized 20 minutes following addition of GAL-101. Following serial dilutions, a solution with GAL-101 < 0.1 nM but containing “blobs” still detoxified a fresh 50 nM Aβ solution.

Conclusions : These results suggest that when a transient GAL-101 peak exceeds a threshold in a toxic Aβ solution it triggers a sustained detoxification, apparently facilitated by the “blobs”. Thus, a single administration delivering retinal peak levels of GAL-101 above threshold for <1 hour might have sustained detoxifying effect in dry AMD and glaucoma patients.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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