New therapeutics for primary hyperoxaluria type 1

Area of Science:

• Nephrology
• Genetics
• Pharmacology

Background:

• Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder.
• It leads to excessive oxalate production in the liver.
• Complications include nephrocalcinosis, kidney stones, chronic kidney disease, and kidney failure.

Purpose of the Study:

• To provide an update on emerging therapies for PH1.
• To review novel treatment strategies targeting oxalate overproduction.

Main Methods:

• Review of current and investigational therapeutic approaches for PH1.
• Focus on RNA interference (RNAi) therapeutics, small molecules, probiotics, and gene editing.

Main Results:

• RNAi therapeutics like Lumasiran and Nedosiran effectively reduce urinary oxalate excretion.
• Other approaches such as stiripentol, lanthanum, and Oxalobacter formigenes are under investigation.
• Gene editing technologies (CRISPR/Cas9) are in preclinical development.

Conclusions:

• Novel PH1 treatments can lower plasma oxalate and urinary oxalate excretion.
• These therapies hold potential to reduce the necessity for combined kidney and liver transplantation.
• Improved treatment options may significantly decrease morbidity and mortality in PH1 patients.