The challenge
- In each disease, the specific protein or peptide is expressed and progressively aggregates into soluble oligomers, protofibrils and insoluble amyloid fibrils. Various antibodies and other agents have been developed to target the insoluble amyloid fibrils, but these are now known to be relatively harmless, so this approach has largely failed.
- Meanwhile, the soluble oligomers are inherently toxic to cells, as they form amyloid pores which puncture holes in cell membranes, just like bacterial pore-forming toxins.
- This causes uncontrolled calcium influx, aberrant signalling and loss of homeostasis, which may be reversible, but leads to progressive cell death and degeneration, which is irreversible.
Our Solution
- We are developing three completely new drug classes, which effectively block, dissolve and degrade these toxic soluble oligomers and pores from within cell membranes:
- Our first-in-class Amporbans effectively block amyloid pores like a plug, thus preventing the uncontrolled influx of calcium ions.
- Meanwhile, our first-in-class Amporins effectively dissolve amyloid pores out of the cell membranes, rather like target-specific detergents.
- And finally, our first-in-class Amportacs actively promote their targeted ubiquitination and degradation by the proteasome.
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