Amplifier Therapeutics, a Cambrian Bio PipeCo, has just dosed the first patient in the Phase 1B clinical trial for their peripherally restricted pan-AMPK activator, ATX-304. In addition, we're pleased to announce that RA Capital and Future Ventures have joined Amplifier's Series A financing, increasing the Series A funding to $33.25 million.
Amplifier Therapeutics, a Sweden-based biopharmaceutical company, is focused on the development of AMP-activated protein kinase (AMPK) activator compounds to treat diseases associated with aging including metabolic conditions, cardiovascular diseases, kidney diseases, and cancer.
Zhang L., Elkahal J., Tianzhen, W.,… Tzahor E.
Senescence plays a crucial role in heart regeneration. Researchers found that transient cardiac fibroblasts senescence in adult mice is essential for regeneration, and is regulated by early growth factor 1 (Egr1). Egr1 facilitates heart regeneration in neonates and agrin-induced regeneration in adults, and leads to the secretion of ECM remodeling proteins, like cathepsins.
Tzahor E. & Dimmeler, S.
Historically, researchers trying to understand and treat cardiac diseases have primarily focused on cardiomyocytes and approaches to replace them after injury. However, the heart is also home to multiple other major cell types, such as fibroblasts, endothelial cells, and immune cells, as well as their surrounding extracellular matrix. Researchers reviewed these different components of the cardiac microenvironment, their contributions in a healthy state and in the setting of disease, and their relevance for potential therapeutic interventions.
Baher, A., Umansky, K.B., Bassat, E…. Tzahor, E.
Previous studies showed that Agrin can promote cardiac regeneration in mice. This research has demonstrated that Agrin can induce similar repair in a clinically relevant porcine model, using procedures and equipment designed for human patients. Furthermore, Agrin's cellular mechanism of action (MoA) was established, showing its effect on the heart cell population essential for repair.
Sarig, R., Rimmer, R., Bassat, E.,… Tzahor, E.
Senescencet often linked to aging, is transient but crucial for development and regeneration. In zebrafish and neonatal mice heart injury models, senescence peaked 4 days post-injury but disappeared by 21 days, mirroring the regenerative pattern seen in salamander limbs. Similar to neonatal cardiac regeneration, Agrin induces a transient wave of cardiac fibroblasts senescence, mimicking the evolutionary conserved regeneration process.
Tzahor, E. & Poss, K.D.
The human heart is continually operating as a muscular pump, contracting, on average, 80 times per minute to propel 8000 liters of blood through body tissues each day. Whereas damaged skeletal muscle has a profound capacity to regenerate, heart muscle, at least in mammals, has poor regenerative potential. This deficiency is attributable to the lack of resident cardiac stem cells, combined with roadblocks that limit adult cardiomyocytes from entering the cell cycle and completing division. Insights for regeneration have recently emerged from studies of animals with an elevated innate capacity for regeneration, the innovation of stem cell and reprogramming technologies, and a clearer understanding of the cardiomyocyte genetic program and key extrinsic signals. Methods to augment heart regeneration now have potential to counteract the high morbidity and mortality of cardiovascular disease.
Bassat, E., Eid Mutlak, Y., Genzelinzakh, A.,…Tzahor, E.
Adult mammalian hearts can't regenerate due to non-dividing cardiomyocytes, but neonatal mouse hearts can within the first week of life. Researchers have identified agrin, a neonatal extracellular matrix component, as crucial for this regeneration. Agrin promotes cardiomyocyte division and enhances heart repair in adult mice, uncovering new possibilities for cardiac regeneration.
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