Hoth Therapeutics has announced positive data from its HT-VA study, conducted under its Cooperative Research and Development Agreement (CRADA) with the US Department of Veterans Affairs and Emory University, demonstrating that parenteral GDNF (Glial Cell-Derived Neurotrophic Factor) directly reprograms liver fat metabolism at the genetic level in a preclinical model of Metabolic-Associated Fatty Liver Disease (MAFLD).

The data highlights statistically significant improvements in key genes responsible for fat production and fat metabolism, positioning GDNF as a potentially differentiated therapeutic approach targeting the root cause of fatty liver disease and metabolic dysfunction.

Unlike existing therapies that primarily focus on weight loss, GDNF directly targets the biological mechanisms responsible for fat accumulation in the liver.

"HT-VA represents a major milestone for Hoth as we expand into high-value metabolic indications," said Robb Knie, Chief Executive Officer, Hoth Therapeutics.

He further added, "These results demonstrate that GDNF is not simply reducing fat, but fundamentally reprogramming how the body produces and metabolises fat at the genetic level. The ability to shut down fat creation while activating fat metabolism differentiates GDNF from existing therapies, including GLP-1 agonists."

The HT-VA study evaluated the effects of parenteral GDNF in a diet-induced obesity and MAFLD model, demonstrating significant metabolic improvements. A Western diet was found to increase liver fat accumulation and metabolic dysfunction, while GDNF treatment markedly improved liver gene expression associated with fat metabolism. The therapy reduced lipogenesis signaling and enhanced metabolic regulation pathways via Pparα activation, indicating improved hepatic lipid handling and overall metabolic efficiency.

From a strategic perspective, these findings position GDNF as a promising candidate for entry into the MAFLD/NASH and obesity markets. Its gene-level mechanism offers clear differentiation from existing GLP-1 therapies and highlights its potential as a first-in-class metabolic reprogramming treatment. Additionally, this development supports Hoth Therapeutics’ expansion beyond its core focus areas of dermatology and oncology.

Hoth plans to advance HT-VA findings into additional preclinical validation studies, evaluate clinical development pathways for metabolic and liver diseases and explore strategic partnerships and collaborations to accelerate development.