Novel Method for Treating Steatosis-Associated Diseases
Unmet Need
Steatosis-associated diseases are marked by the infiltration of the liver with fatty acids. Liver steatosis occurs in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), as well as rare diseases such as glycogen storage disease type I (GSD I). Current standard of care focuses on ameliorating symptoms or making lifestyle changes which cannot correct the underlying problem. More recently, gene therapies have been developed for rare diseases, including GSD I. However, these gene therapies have had varying levels of success and are often plagued by dosing issues and lack of durability. Any gene therapy administered to patients with NAFLD or NASH, affecting cumulatively up to 25% of the US population, would face similar issues. This includes gene therapies for conditions unrelated to NAFLD or NASH, given their high prevalence. There is a clear need for a gene therapy regimen that is accessible to patients with liver steatosis from any cause.
Technology
Duke inventors have developed a treatment method that is designed to reduce lipid accumulations in the liver. This is intended to be used to treat steatosis-associated diseases including GSD I, as well as other inherited liver disorder in a patient who also has NAFLD or NASH. Specifically, this treatment method is comprised of an autophagy inducing agent, a lysosomal enzyme, or both. In steatosis-associated diseases there is an influx of triglycerides into the liver and autophagy, or degradation, of these triglycerides is impaired. Duke inventors investigated whether inducing autophagy of lipid stores would lead to improved metabolism in a GSD I background. They demonstrated that pharmacological induction of autophagy can lead to a correction in hepatic fat levels both in vitro and in vivo models of GSD Ia.
Other Applications
This technology could also be used as an adjuvant therapy to reduce dosage requirements for gene therapy or mRNA therapy in patients with NAFLD or NASH, or steatosis-associated rare diseases such as GSD I.
Advantages
- Targeted treatment that avoids the pitfalls of AAV based gene therapy
- Treats a root cause of disease rather than symptoms
- Combination therapy is comprised of drugs that are already FDA approved for other uses