Statistically Significant Reduction in Srebf1 (Fat Production) and Increased Pparα (Fat Metabolism) Position GDNF as Next-Generation Therapy for MAFLD and Obesity
NEW YORK, April 13, 2026 /PRNewswire/ -- Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company, today announced positive data from its HT-VA study, conducted under its Cooperative Research and Development Agreement (CRADA) with the U.S. 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.
- Statistically significant reduction in Srebf1, a key gene driving fat production in the liver
- Increased expression of Pparα, a central regulator of fat metabolism and fat burning
- GDNF outperformed semaglutide in key gene expression markers tied to liver fat regulation
- Demonstrated broad metabolic impact at the genetic level, not just weight reduction
Unlike existing therapies that primarily focus on weight loss, GDNF directly targets the biological mechanisms responsible for fat accumulation in the liver.
- Srebf1 reduction → less fat being created
- Pparα activation → more fat being burned
- Net effect → reprogramming of liver metabolism
This dual mechanism suggests GDNF may offer a disease-modifying approach for MAFLD, obesity, and related metabolic disorders.
"HT-VA represents a major milestone for Hoth as we expand into high-value metabolic indications," said Robb Knie, Chief Executive Officer of Hoth Therapeutics.
"These results demonstrate that GDNF is not simply reducing fat, but fundamentally reprogramming how the body produces and metabolizes 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."
SCIENTIFIC SUMMARY (HT-VA STUDY)
The HT-VA study evaluated the effects of parenteral GDNF in a diet-induced obesity and MAFLD model.
Key observations include:
- Western diet significantly increased liver fat accumulation and metabolic dysfunction
- GDNF treatment significantly improved liver gene expression linked to fat metabolism
- Reduced lipogenesis signaling (Srebf1) and enhanced metabolic regulation pathways (Pparα)
- Gene expression changes support improved hepatic lipid handling and metabolic efficiency
STRATEGIC IMPLICATIONS
- Entry into MAFLD/NASH and obesity markets
- Differentiation vs. GLP-1 therapies through gene-level mechanism
- Potential for first-in-class metabolic reprogramming therapy
- Expansion beyond Hoth's core dermatology and oncology pipeline
NEXT STEPS
Hoth plans to:
- Advance HT-VA findings into additional preclinical validation studies
- Evaluate clinical development pathways for metabolic and liver diseases
- Explore strategic partnerships and collaborations to accelerate development
About Hoth Therapeutics, Inc.
Hoth Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative, impactful, and ground-breaking treatments with a goal to improve patient quality of life. We are a catalyst in early-stage pharmaceutical research and development, elevating drugs from the bench to pre-clinical and clinical testing. Utilizing a patient-centric approach, we collaborate and partner with a team of scientists, clinicians, and key opinion leaders to seek out and investigate therapeutics that hold immense potential to create breakthroughs and diversify treatment options. To learn more, please visit https://ir.hoththerapeutics.com/ .
Forward-Looking Statement
This press release includes forward-looking statements based upon Hoth's current expectations, which may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws, and are subject to substantial risks, uncertainties, and assumptions. These statements concern Hoth's business strategies; the timing of regulatory submissions; the ability to obtain and maintain regulatory approval of existing product candidates and any other product candidates we may develop, and the labeling under any approval we may obtain; the timing and costs of clinical trials, and the timing and costs of other expenses; market acceptance of our products; the ultimate impact of the current coronavirus pandemic, or any other health epidemic, on our business, our clinical trials, our research programs, healthcare systems, or the global economy as a whole; our intellectual property; our reliance on third-party organizations; our competitive position; our industry environment; our anticipated financial and operating results, including anticipated sources of revenues; our assumptions regarding the size of the available market, benefits of our products, product pricing, and timing of product launches; management's expectation with respect to future acquisitions; statements regarding our goals, intentions, plans, and expectations, including the introduction of new products and markets; and our cash needs and financing plans. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. You should not place reliance on these forward-looking statements, which include words such as "could," "believe," "anticipate," "intend," "estimate," "expect," "may," "continue," "predict," "potential," "project" or similar terms, variations of such terms, or the negative of those terms. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee such outcomes. Hoth may not realize its expectations, and its beliefs may not prove correct. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described in the section titled "Risk Factors" in Hoth's most recent Annual Report on Form 10-K and Hoth's other filings made with the U. S. Securities and Exchange Commission. All such statements speak only as of the date made. Consequently, forward-looking statements should be regarded solely as Hoth's current plans, estimates, and beliefs. Investors should not place undue reliance on forward-looking statements. Hoth cannot guarantee future results, events, levels of activity, performance, or achievements. Hoth does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events, or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law.
Investor Contact:
LR Advisors LLC
Email: investorrelations@hoththerapeutics.com
www.hoththerapeutics.com
Phone: (678) 570-6791
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SOURCE Hoth Therapeutics, Inc.
