Rather than targeting the pathogenic proteins themselves, which lack a stable structure and are therefore hard to reach, AmyP53, an adaptive peptide, targets their anchoring point in the membrane: gangliosides. An entirely new approach, based on the conformational flexibility of the peptide, never attempted before.
To assemble into pores, the Aβ (Alzheimer’s disease) and α-synuclein (Parkinson’s disease) proteins must first bind to specific membrane gangliosides: GM1 in Alzheimer’s disease, GM3 in Parkinson’s disease. AmyP53 binds to these gangliosides and prevents this binding. Deprived of their anchoring point, the proteins can no longer oligomerise in the membrane: no pore, no calcium influx, no neurotoxic cascade.
From the outset, the design of AmyP53 incorporated multiple biochemical, biophysical and pharmacological parameters, in order to avoid the classic pitfalls of drug candidate development.
AmyP53 stems from the decoding of a biological code: the one governing the recognition of gangliosides by amyloid proteins. It was therefore designed to bind its target with high specificity, remain stable and be administered nasally. Its small size makes it an easy peptide to synthesise.
By targeting a common pathological mechanism, AmyP53 is the first therapeutic solution specifically designed to treat two major neurodegenerative diseases: Alzheimer’s and Parkinson’s.
AmyP53 thus opens up a new class of drugs, whose potential extends to other diseases involving intrinsically disordered proteins and gangliosides.
The video below compares an unprotected membrane, in which amyloid proteins form pores, with a membrane protected by AmyP53.
Aβ or α-synuclein proteins bind to the gangliosides concentrated in the rafts of the brain cell membrane.
Anchored in the membrane, they assemble into oligomers that form calcium-permeable pores. The influx of Ca2+ triggers the neurotoxic cascade: Tau hyperphosphorylation, mitochondrial stress, neuronal death.
AmyP53 occupies the gangliosides upstream: the proteins can no longer bind to them. No pore, no Ca2+ influx, no neurotoxic cascade.
of Alzheimer’s patients also present α-synuclein pathology, the hallmark of Parkinson’s disease.
of advanced Alzheimer’s and Lewy body disease cases present at least one other proteinopathy.
Mixed forms: Lewy body diseases
Overlap of Alzheimer’s and Parkinson’s pathologies
Data from post-mortem studies. Sources: Robinson J.L. et al., Brain, 2018
Compta Y. & Revesz T., Journal of Parkinson’s Disease, 2021.
Despite decades of research and billions invested by the pharmaceutical industry, no treatment can currently stop the progression of Alzheimer’s and Parkinson’s diseases. AmyP53 stands apart from current approaches on every key point.
| Conventional approaches targeting amyloid proteins | AmyP53 | |
|---|---|---|
| Target | Conventional approachesAmyloid proteins or their aggregates (plaques) | AmyP53Gangliosides, the common membrane anchoring point of amyloid proteins |
| Stage of action | Conventional approachesAfter aggregates have formed | AmyP53At the earliest stage, before pores form |
| Indications | Conventional approachesOne disease per molecule | AmyP53Alzheimer’s and Parkinson’s with a single molecule, which also targets co-pathologies |
| Nature | Conventional approachesMainly monoclonal antibodies | AmyP53A peptide of 12 natural amino acids, easy to synthesise |
| Administration | Conventional approachesIntravenous infusion or injection | AmyP53Nasal spray, non-invasive |
Strong chemical and biological stability. No toxicity at the maximum doses tested on neurons, astrocytes and endothelial cells.
No toxicity at the highest doses tested in animal models (rodents and non-rodents). No inflammatory reaction after repeated intranasal administration. Excellent safety profile.
AmyP53 inhibits the toxicity of the Aβ and α-synuclein proteins, amyloid pore formation and the Ca2+ fluxes involved in Alzheimer’s and Parkinson’s diseases.
AmyP53 has demonstrated therapeutic efficacy in models of Alzheimer’s disease and Parkinson’s disease. In an animal model of Parkinson’s disease induced by α-synuclein oligomers, it notably prevents the loss of dopaminergic neurons.
Our researchers decode the biological code that controls the recognition of gangliosides by amyloid proteins.
AmyP53 is protected by patent EP14305353: Europe, United States, Canada, China, Japan.
All preclinical studies of AmyP53 have been completed.
First administration of AmyP53 in humans.
AmyP53 will be administered as a nasal spray. This non-invasive route reaches the brain directly, via the olfactory nerve and the trigeminal nerve. It offers greater comfort to patients, their families and caregivers.
To design this device, AmyPore collaborated with Aptar Pharma, a global leader in nasal drug delivery systems. Six devices were evaluated, including two specifically designed for nose-to-brain delivery: the Neurospray™ and Neurospray™ Preservative-Free. The results, published in Pharmaceutics in 2026, show that:
These results validate the Neurospray™ devices for the clinical development of AmyP53, ahead of the Phase 1 trial.
Gangliosides are also involved in other neurodegenerative diseases (amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease), in many infectious diseases, in cancer metastasis and in type 2 diabetes. Our platform harnesses this potential.
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