Hoth Therapeutics’ GDNF Cuts Srebf1 and Boosts Pparα, Outpacing Semaglutide
Hoth Therapeutics’ HT-VA preclinical trial under its VA CRADA showed parenteral GDNF achieved statistically significant reduction in Srebf1 fat-production gene and upregulated Pparα fat-metabolism gene, outperforming semaglutide in key liver-expression markers. This dual mechanism suggests potential for disease-modifying treatment in MAFLD and obesity.
1. HT-VA Preclinical Study Design
Under a Cooperative R&D Agreement with the U.S. Department of Veterans Affairs and Emory University, Hoth’s HT-VA study administered parenteral GDNF in a diet-induced obesity and MAFLD preclinical model to assess gene-level impacts on liver fat metabolism.
2. Gene Expression Outcomes
GDNF treatment produced a statistically significant reduction in Srebf1, the gene responsible for lipogenesis, and a marked upregulation of Pparα, enhancing pathways for fatty acid oxidation and metabolic regulation.
3. Comparison with Semaglutide
In head-to-head preclinical markers, GDNF outperformed semaglutide by more effectively downregulating fat-creation signals and activating fat-burning pathways, indicating a potentially differentiated mechanism of action.
4. Strategic Implications and Next Steps
Hoth plans to advance these findings into further preclinical validation, explore clinical development pathways for MAFLD and obesity, and seek strategic partnerships to accelerate progress toward a first-in-class metabolic reprogramming therapy.