Repairing the septin skeleton in neurons to treat Alzheimer’s disease: While recent Alzheimer’s disease (AD) treatments targeting amyloid plaques have shown they can slow cognitive decline, they are primarily effective only in early stages and do not reverse existing symptoms. To provide durable relief across the full spectrum of the disease, we need therapies that go beyond plaque removal to actively protect brain cells and restore their function. 

The innovation: remynd’s project targets the septin cytoskeleton, which acts as the internal "scaffolding" of brain cells. In AD, toxic proteins (tau) damage this scaffolding, causing it to fall apart. This structural collapse leads to a dangerous overload of calcium inside the cell, which drives neurodegeneration leading to dementia. remynd has developed a "molecular glue" designed to repair this damage. By physically binding the septin proteins together, the glue re-stabilizes the cellular skeleton. This restores normal calcium levels, protects the neuron from dying, and rapidly improves synaptic function required for cognition.

From proof-of-concept to optimized therapy: We previously tested a first-generation version of this drug (REM127) in patients. The results were highly encouraging: the drug improved markers reflecting brain function, cognition and disease progression. However, that specific version caused liver side effects, requiring us to discontinue it. We have now successfully developed an optimized successor, REM392. Studies in the laboratory confirm it offers the same powerful brain-protective benefits as its predecessor but without the liver toxicity.

Project goal: Having passed safety and efficacy tests in model systems, REM392 is ready for patient trials. This proposal seeks funding to supports activities needed to conduct a Phase 2 clinical trial to assess REM392 efficacy in AD patients. If successful, this therapy could represent a breakthrough, offering both symptomatic relief and disease-modifying effects, either as a standalone tablet or in combination with existing antibody treatments.