Preclinical studies test novel gene therapy for treating IgA nephropathy

IgA nephropathy is an autoimmune kidney disease, and complement, a component of the innate immune system, plays a role in the condition’s pathogenesis. Investigators have developed and tested a novel gene therapy that enters kidney cells and enables them to block complement activation. The research was presented at ASN Kidney Week 2024, held October 23–27.

The gene therapy, called PS-002, uses a modified virus to treat kidney cells called podocytes. Administration of PS-002 in a mouse model of IgA nephropathy reduced signs of kidney dysfunction, lowered complement deposition, and ameliorated kidney scarring and other structural characteristics of kidney disease. In pigs, treatment with PS-002 resulted in elevated and prolonged gene expression in kidney tissues, with no safety issues.

“Our data demonstrate that targeting podocytes to modulate complement activation is an effective therapeutic strategy, and PS-002 paves the way to become the first gene therapy in development for the treatment of IgA Nephropathy,” said corresponding author Ambra Cappelletto, Ph.D., of Purespring Therapeutics, in London.

“Purespring’s gene therapy platform exemplified by PS-002 demonstrates therapeutic genetic material can be delivered with high efficiency to podocytes, opening up a new and highly differentiated modality with the potential to treat a broad range of kidney diseases.”