GPR17 program
Role of myelin in CNS
Myelin is a lipid-rich substance that insulates neuronal axons to facilitate the rapid transmission of electrical signals and enable efficient communication between cells. Research has shown that myelin integrity and plasticity are essential for learning, memory, and overall cognitive performance.
Additionally, the myelin sheath provides neurons with metabolic support and protection from damage. Myelin is produced by mature oligodendrocytes, a type of specialized glia in the central nervous system.
Myrobalan's GPR17 antagonist mechanism of action
In the central nervous system, oligodendrocyte precursor cells (OPCs) differentiate into mature myelinating oligodendrocytes. The G-protein coupled receptor 17 (GPR17) inhibits pathways and gene expression that regulate the timing of oligodendrocyte development and serves as an intrinsic brake to maturation of OPCs into myelinating oligodendrocytes.
In the diseased or damaged CNS, myelin is lost and neurons are unable to communicate with each other efficiently. The natural repair process of remyelination is often incomplete due to insufficient maturation of OPCs into myelinating oligodendrocytes. This eventually leads to progressive deterioration of neurological function.
GPR17 antagonism stimulates and accelerates CNS remyelination, potentially offering neuroprotective effects and slowing disease progression in patients with demyelinating disorders. Our preclinical studies in primary OPCs, human iPSC-derived oligodendrocytes, and animal models of demyelination demonstrate that Myrobalan's compounds are potent, highly selective, and brain-penetrant. With no other GPR17 antagonist having entered clinical trials to date, Myrobalan's program has the potential to achieve first-in-class status across multiple indications. We are dedicated to employing biomarkers to identify patients most likely to benefit from our remyelination therapy during clinical development.