Novel HNF4α-based nucleotide therapy for end-stage liver disease with cirrhosis
Official title: Novel Nucleotide HNF4α Transcriptional Modulation for End Stage Liver Disease with Cirrhosis
Funded at Masterswitch, INC. · NIH-11408899 · Data updated 2026-11-12
A new therapy using a nucleotide-LNP to restore a key liver gene could improve liver function and survival for people with severe cirrhosis or liver failure.
Quick facts
| Grant type | Sbir 2 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Masterswitch, INC. NIH-funded |
| Lab location | 1 site (Wilmington, France) |
| Project start | September 7, 2026 |
| Project end | June 30, 2028 |
| Funding year | 2026 |
| Award (this year) | $1,189,285 |
| NIH project number | 1R44DK148355-01 |
| Project ID | NIH-11408899 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults with decompensated cirrhosis or ESLD who are candidates for experimental therapies and have appropriate medical clearance.
✕Less likely to help
Patients with advanced organ failure not eligible for nucleotide-LNP therapy or who cannot tolerate liver-directed delivery.
What this research studies
This project aims to deliver a nucleotide that re-expresses the liver transcription factor HNF4α directly to liver cells using lipid nanoparticles, with the goal of restoring hepatocyte function in people with decompensated cirrhosis and ESLD. The work builds on prior proof-of-concept studies in human and animal models showing functional improvements after treatment. If successful, this approach could provide a non-transplant therapy option for patients who cannot access or are unsuitable for transplant. The grant supports preclinical and early clinical development to evaluate safety, delivery, and preliminary efficacy.
Why it matters
Potential benefit: If successful, patients could experience improved liver function and survival without immediate need for transplantation.
How similar studies have gone: Preclinical studies have shown promising improvements in hepatocyte function and survival with HNF4α restoration using nucleotide-LNPs.
Where this research is happening
-
Masterswitch, INC.
Wilmington, France Active
Researchers
- Principal investigator: Brooke, Christopher — Masterswitch, INC.
- Study coordinator: Brooke, Christopher
Related research
Other NIH-funded projects on the same topics.
-
Statin therapy for people with compensated cirrhosis
A big, long-term study at a major university is looking at whether statins can help people with compensated cirrhosis live longer and feel better.
-
Liver Cirrhosis Network: Centers for Clinical Research
A multicenter study in people with cirrhosis from different causes (including HIV, NASH, and alcohol-related liver disease) to collect data and samples and test new ways to predict and monitor disease progression.
-
Outcomes in cirrhosis from different causes and the role of HIV and simvastatin
This study looks at how cirrhosis from alcohol, HIV, and other causes affects patients and whether simvastatin can influence outcomes.
-
Liver Cirrhosis Network: Mayo Clinic's Clinical Research Center
A Mayo Clinic-led project will follow and help people with compensated cirrhosis, using data, imaging, and a big AI tool to predict when complications may happen and test whether a statin can improve outcomes.
-
Understanding how risk factors affect progression of cirrhosis and response to statins in patients with cirrhosis
This project follows people with cirrhosis to see what factors speed up their liver disease and whether statin medicines help prevent worsening.
-
Cirrhosis Network study to understand mortality and therapies
A large, multi-center study in people with cirrhosis to find better ways to predict deaths and test the potential of statins to prevent complications like liver cancer and liver failure.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.