By blocking a key step in the neurodegenerative process, Galimedix’s technology prevents the formation of toxic amyloid beta (Aβ) oligomers and protofibrils instead of removing already formed toxic species like most products in development and on the market do. Pre-clinical data support that our product candidates can block formation and remove the whole spectrum of possible toxic Aβ oligomers and do this in both the brain and the retina.
Current Understanding of Aβ Pathology as Cause of Neurodegeneration
Many studies have indicated that toxic Aβ oligomers and protofibrils are an underlying cause of neurodegenerative diseases of the eye. Recent approvals and promising Phase 3 results of anti-Aβ drugs also have validated them as a key target in Alzheimer’s disease.
As highlighted below, normal Aβ monomers are important to neuronal function but misfolding of these monomers can lead to the development of toxic forms of Aβ that can be highly damaging to the retina and brain cells. This process is outlined here.
Toxic Aβ damages neural cells, which leads to activation of the complement cascade, loss of cell function, apoptosis and eventual death.
Aβ – A Key Target for Both Eye and Brain
Evidence suggests the same mechanisms are involved in retinal diseases and the devastating brain condition, Alzheimer’s disease (AD). These striking similarities show that the accumulation of toxic Aβ is a key overlapping feature between three neurodegenerative disorders that affect millions of older adults worldwide: AD, glaucoma, and dry age-related macular degeneration (dry AMD). All three disorders are chronic, age-related disorders with no known cure and lead to irreversible loss of function.
Product Candidates Designed to Prevent Toxic Aβ Oligomer Formation at the Outset
Galimedix is developing cutting-edge orally and topically administered Aβ aggregation modulators that target the beginning of the Aβ peptide aggregation cascade. Our candidates GAL-101 and GAL-201 act upstream to most other Aβ-targeting approaches on the market and in advanced development, potentially enabling them to effectively impact disease progression without disturbing normal neuronal function.
As shown above, Galimedix’s molecules prevent the formation of all toxic Aβ oligomers that drive neurodegeneration at the source by binding to a specific motif only exposed in the misfolded monomers, triggering the clustering of these misfolded Aβ monomers and preventing the assembly of harmful oligomers. These clusters collect and detoxify Aβ.
Trigger effect provides lasting efficacy beyond drug administration
Of interest, the clusters attract further misfolded monomers so that this process continues even when there is no drug left in the tissue. This novel self-propagating detoxification or “trigger effect” results in a sustained effect lasting far longer than the time a single administration of the drug remains at therapeutic levels in the system. This trigger effect has been patented by Galimedix.