Restoring lysosome acidity to help fatty liver (MASLD)
Official title: Lysosomal Regeneration (LysoGen) and Rescue as a Treatment for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Funded at Boston University (Charles River Campus) · NIH-11195154 · Data updated 2026-11-12
Researchers are developing an acid-releasing therapy to help liver cells clear fat buildup in people with metabolic-dysfunction associated steatotic liver disease (MASLD).
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Boston University (Charles River Campus) NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | September 20, 2024 |
| Project end | July 31, 2029 |
| Funding year | 2025 |
| Award (this year) | $619,776 |
| NIH project number | 5R01DK141923-02 |
| Project ID | NIH-11195154 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults with metabolic-dysfunction associated steatotic liver disease (MASLD), especially middle-aged and older individuals with fatty liver related to metabolic risk factors, would be the likely candidates.
✕Less likely to help
People without MASLD, those whose liver disease is primarily due to alcohol, or patients with advanced cirrhosis are unlikely to benefit from this therapy.
What this research studies
This project develops LysoGen, an injectable polymer designed to release acid inside your liver cells' lysosomes so they can regain normal acidity and resume clearing damaged material and excess fat. The therapy contains a strong diacid (tetrafluorosuccinic acid, TFSA) built into a biodegradable polyester copolymer that is activated by the mildly acidic lysosomal environment. It is designed to sense lysosomes with pH around 5.7–6 and lower the pH to a healthier 4–5, restoring autophagic flux. Researchers will first test the approach in laboratory and preclinical models with the goal of advancing to human testing to see if liver fat and autophagosome buildup are reduced.
Why it matters
Potential benefit: If successful, this approach could help liver cells clear excess fat and damaged material, potentially slowing or reversing MASLD progression.
How similar studies have gone: Targeting lysosomal acidification is a novel strategy with promising laboratory results for autophagy-related problems but has limited clinical testing to date.
Where this research is happening
-
Boston University (Charles River Campus)
Boston, United States Active
Researchers
- Principal investigator: Grinstaff, Mark W. — Boston University (Charles River Campus)
- Study coordinator: Grinstaff, Mark W.
Related research
Other NIH-funded projects on the same topics.
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Them1’s role in fat metabolism and MASLD progression
Aims to understand how a fat-regulating protein (Them1) affects energy use in fat and liver, and how this could contribute to MASLD in people who are overweight.
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Understanding MASLD progression to MASH and liver cancer in Alaska Native communities
A patient-facing overview of a study that looks at why a common liver disease progresses to more serious conditions in Alaska Native and American Indian people.
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Pediatric MASLD: a blood test to detect liver disease progression in kids
A child-friendly blood test is being developed to spot liver disease progression in kids with MASLD without needing biopsies.
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Growth Hormone and DNA Repair in Children's MASLD outcomes
A small, patient-friendly study will explore how growth hormone and the ATM DNA repair pathway affect liver health in children with MASLD.
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Isocaloric navy bean substitution for MASLD with fibrosis
A small, patient-friendly trial tests whether swapping in navy beans for some daily calories can help adults with MASLD and liver fibrosis without changing total calories.
-
S100A9+ immune cells driving liver scarring in MASLD/MASH
Affects people with MASLD/MASH may benefit from a better understanding of how certain immune cells contribute to liver fibrosis and how to stop it.
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.