New Podocyte-Targeted Treatments for Focal Segmental Glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis FSGS, the leading glomerular cause of kidney failure, is characterized by progressive glomerulosclerosis that leads to declining kidney function. The common theme across all FSGS patients is podocyte dysfunction and loss reduced podocyte number directly underlies glomerulosclerosis, and hereditary FSGS is caused by mutated genes that disrupt the podocyte cytoskeleton. Despite increasing evidence indicating that podocytes are the cells primarily injured in FSGS, the current mainstay in FSGS treatment is immunosuppressant therapy that does not directly target these cells, leading to adverse side effects. Moreover, these drugs do not halt disease progression in all patients. FSGS remains notoriously difficult to treat, highlighting the clinical need for novel, podocyte-targeted treatment strategies to increase therapeutic efficacy and mitigate side effects. Many lines of evidence support targeted podocyte delivery as a viable approach podocytes are highly endocytotic, many frontline drugs exhibit direct effects on podocytes, and experimental drugse.g. Bis-T-23 that protect the podocyte cytoskeleton are effective in animal models of FSGS. However, to date there are no technologies for targeted drug delivery to podocytes.