reMYND announces publication in Science of novel drug target with potential for development into transformative treatments for Alzheimer’s disease

reMYND NV, a biotech company tackling neurodegeneration, is pleased to announce the publication in the prestigious journal Science of research detailing the identification of first-in-class small-molecule septin modulators with neuroprotective efficacy.

Abnormal calcium signalling is a central pathophysiological process in Alzheimer’s disease (AD) implicated in several key processes associated with the disease, including the deposition of amyloid β (Aβ) and tau protein, abnormal synaptic plasticity, and neuronal death. However, given the essential role of calcium-signalling in communication and physiology of nerve cells, non-selective manipulation of calcium concentration inside nerve cells may cause serious adverse effects.

reMYND’s preclinical research was set out to identify small molecules that could normalise calcium levels in a disease context only without affecting its “normal” physiological functions. A promising “hit” from initial screening of candidates was optimized into a class of related molecules. It was observed that these compounds interact with proteins known as septins. Septins are GTP-binding proteins and form part of the cytoskeleton by assembling into filament structures. Further findings showed that the compounds serve as a “molecular glue” to restore the structural integrity of septin filaments, which prevents unwanted activation of store-operated calcium channels. By stabilizing septin structures and regulating calcium channel activity, these molecules may tackle a fundamental issue in Alzheimer’s disease (AD). This approach not only offers rapid symptomatic relief but also contributes to modifying the progression of the disease.

The research highlights the neuroprotective qualities of septin modulation to restore calcium homeostasis. The compounds fully restored hippocampal long-term potentiation (associated with the formation of new memories), saved spatial memory deficits and stabilized brain oscillatory activity. The formation of Αβ plaques and hyperphosphorylated tau aggregates was also reduced.

Promising signals, mirroring the neuroprotective effects reported preclinically, have been observed clinically in a Phase 2a study, along with cognitive improvement, further validating the therapeutic potential of septin modulators. These clinical effects have been observed with a first-generation compound, albeit within a narrow therapeutic window. An optimized second-generation molecule has been developed and is currently progressing through IND-enabling studies.

The full article, Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer’s disease can be accessed here: https://doi.org/10.1126/science.add6260

Dr Gerard Griffioen, Chief Scientific Officer of reMYND and lead author of the paper, said: “The findings we are sharing today highlight the neuroprotective effects of our septin modulators and strengthen our focus on restoring calcium homeostasis in order to treat Alzheimer’s. We remain fully focussed on translating these findings in the clinic.”

Jim Van heusden, interim Chief Executive Officer of reMYND, added: “In the field of Alzheimer’s research, there is a significant demand for treatments that provide substantial symptomatic and disease-modifying clinical benefits. We are optimistic about the potential of septin modulators as a transformative therapy for this large, severely underserved patient population. We look forward to sharing more updates on our compounds in due course.”