Synapse loss is associated with some of the most devastating and debilitating central nervous system (CNS) conditions, including Alzheimer’s, ALS and schizophrenia. Much of CNS drug development has focused on mitigating the accumulation of damaging proteins, including mutant SOD1 in ALS, amyloid beta in Alzheimer’s, or fine-tuning receptor signaling, such as dopaminergic pathways in schizophrenia. But synapses are the brain’s physical wiring, and current therapeutic strategies do not rebuild connections that have already been lost. What if we could instead repair that underlying circuitry across multiple diseases with a single, small molecule regenerative therapy?
In this interview with Drug Discovery News, Spinogenix’s Chief Science Officer, Peter Vanderklish, and Chief Development Officer, Sharron Gargosky, discuss the clinical potential of tazbentetol, a first-in-class regenerative therapeutic addressing synapse loss, a core driver of symptoms in neurodegenerative and neuropsychiatric conditions. As a Transient Activator of Glutamatergic Synaptogenesis (TAGS), tazbentetol – Spinogenix’s “hit and run” approach to synaptogenesis – is designed to restore synaptic function without requiring continuous exposure, while avoiding the risks that can be associated with other classes of rapid-acting synaptogenic compounds.
Building on an encouraging safety profile and early signals of efficacy in synapse loss, Spinogenix established a novel development strategy to simultaneously evaluate tazbentetol in ALS, Alzheimer’s and schizophrenia. Central to this approach is electroencephalography (EEG), which records brain activity patterns linked to synaptic transmission. Signature changes in the patterns of EEG recordings have been defined in ALS, Alzheimer’s and schizophrenia, marking disease-related changes in neural processing that are correlated with symptoms. By using quantitative EEG as a pharmacodynamic biomarker, early clinical trials have provided consistent, empirical evidence that tazbentetol has the potential to improve disease-related changes in synaptic communication in all three conditions. Such objective and quantitative neurophysiological evidence adds confidence to the potential benefits of tazbentetol that have been observed using standard behavioral outcomes.
“What’s particularly powerful about EEG is that it’s largely independent of placebo effects,” Dr. Gargosky told Drug Discovery News. “You can’t consciously influence those signals in the way you might with subjective measures. So, it provides a clean, objective readout of brain activity that we can then correlate with clinically meaningful outcomes.”
Read the full article in Drug Discovery News to see how synaptic regeneration could become the “missing piece” that shifts CNS therapy from merely slowing decline to actively restoring function:
https://www.drugdiscoverynews.com/can-one-drug-repair-the-brain-across-multiple-cns-diseases-17191