Blocking a newly discovered enzyme stopped weight gain and lowered cholesterol in mice, and other labs are now finding their own fat-metabolism switches
In December 2025, researchers at University Hospitals in Cleveland and Case Western Reserve University reported an enzyme the body needs to build fat, called SCoR2. Blocking it in mice stopped weight gain, protected the liver and lowered bad cholesterol, the team wrote in <em>Science Signaling</em>.
The team said then that human testing was about 18 months away, which points to mid-2027. No trial has been announced since. Other labs are working the same problem from other angles: in October 2026, ScienceDaily reported that switching off a protein called Mitch made human cells burn more fat and stopped new fat cells from forming.
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Curated perspectives — historical figures and your fellow readers.
Fictional AI pastiche — not real quote.
"A fine discovery, this enzyme switch! Though I observe that Nature gives us hunger to make us work, and now Science offers to make us thin whilst we sit idle. I suspect the greatest benefit will be to those who can afford both the feast *and* the cure—a modern alchemy that turns gold into slenderness."
A nonprofit institute that accelerates academic discoveries through the high-risk stages of drug development by providing funding, pharmaceutical expertise, and business development support.
A private research university in Cleveland with strong programs in medicine and biomedical engineering, frequently collaborating with University Hospitals on translational research.
October 1998 October 2026
ScienceDaily reported that switching off a protein called Mitch made human cells burn more fat and stopped new fat cells from developing, following mouse experiments that showed resistance to obesity. It is a different protein from SCoR2.
Science Daily and other outlets reported on the SCoR2 findings, highlighting the potential for a new class of obesity drugs targeting fat production rather than appetite.
Stamler's team published findings in <em>Science Signaling</em> identifying SCoR2 as an enzyme required for fat production, showing that blocking it prevented weight gain and lowered cholesterol in mice.
The FDA approved semaglutide as the first GLP-1 therapy indicated for MASH, expanding the proven applications of obesity drugs to liver disease.
The FDA approved resmetirom (Rezdiffra) as the first drug specifically indicated for metabolic dysfunction-associated steatohepatitis, demonstrating demand for liver-targeted obesity treatments.
The FDA approved Wegovy (semaglutide 2.4mg) for chronic weight management, marking a turning point in obesity pharmacotherapy with a GLP-1 receptor agonist achieving significant weight loss.
Jonathan Stamler established the Harrington Discovery Institute at University Hospitals Cleveland Medical Center to accelerate translation of academic discoveries into drugs.
Robert Furchgott, Louis Ignarro, and Ferid Murad won the Nobel Prize in Physiology or Medicine for discovering nitric oxide as a cardiovascular signaling molecule, establishing the scientific foundation for understanding NO's role in metabolism.
Discussed by: Harrington Discovery Institute leadership and biotech industry analysts tracking obesity drug pipelines
Human trials begin within the projected 18-month window and show acceptable safety with meaningful weight loss. A major pharmaceutical company licenses the drug or acquires the development program, accelerating later-stage trials. This outcome would validate a new mechanism distinct from GLP-1 agonists and could eventually offer patients an alternative with potentially different side effect profiles.
Discussed by: Drug development experts and observers of obesity drug history, including the fen-phen withdrawal
The mechanism that looked promising in mice fails to translate to humans, either because the weight loss effect is too modest, side effects emerge, or the drug proves difficult to deliver effectively. Given the history of obesity drugs being withdrawn for unexpected cardiovascular or other toxicities, regulators may impose stringent safety monitoring requirements that slow or halt development.
Discussed by: Academic researchers studying S-nitrosylation and metabolism at institutions beyond Cleveland
Even if this specific drug candidate faces obstacles, the underlying discovery that SCoR2 controls fat synthesis through nitric oxide signaling opens new research directions. Other groups pursue related targets in the denitrosylation pathway, potentially leading to multiple drug candidates from different companies approaching the same fundamental mechanism.
Discussed by: Healthcare economists and pharmaceutical industry analysts at IQVIA and similar firms
By the time an SCoR2 inhibitor could reach market approval (earliest 2030), the GLP-1 drug class may have expanded to include oral formulations, monthly injections, and combination therapies that address multiple conditions. A novel mechanism drug would need to demonstrate clear advantages—better tolerability, different patient populations, or lower cost—to gain significant market share against entrenched competitors.
3 moments from history that rhyme with this story — and how they unfolded.
The FDA requested withdrawal of fenfluramine and dexfenfluramine from the market after reports linked the combination to heart valve damage. At its peak, over 18 million prescriptions were written annually. About 30% of users showed abnormal echocardiograms even without symptoms.
Manufacturer American Home Products (later Wyeth) eventually paid over $13 billion in legal damages to affected patients.
The FDA significantly tightened cardiovascular safety requirements for obesity drugs, requiring long-term outcome studies before approval and creating lasting skepticism about weight-loss medications.
Any new obesity drug mechanism faces heightened scrutiny for cardiovascular effects. The SCoR2 inhibitor's cholesterol-lowering action will need extensive cardiac safety data given this history.
Robert Furchgott, Louis Ignarro, and Ferid Murad shared the Nobel Prize in Physiology or Medicine for discovering that nitric oxide—a gas and free radical—functions as a critical signaling molecule in the cardiovascular system, controlling blood vessel dilation.
The prize validated decades of research and accelerated pharmaceutical interest in nitric oxide pathways, contributing to drugs like sildenafil (Viagra).
Stamler's subsequent work on S-nitrosylation—how NO attaches to proteins—built directly on this foundation, eventually leading to the SCoR2 discovery 27 years later.
The SCoR2 finding represents a new chapter in nitric oxide research, showing the molecule's role extends beyond blood vessels to fat metabolism.
The FDA approved semaglutide 2.4mg (Wegovy) for chronic weight management in adults, marking the first new obesity drug in seven years. Trial participants lost an average of 15% of body weight, far exceeding previous medications.
Demand vastly outstripped supply, creating shortages that persisted for years. Novo Nordisk's market capitalization surged past $400 billion.
GLP-1 agonists transformed obesity from a condition with limited pharmaceutical options to one with multiple effective treatments. By 2025, the class generated over $39 billion in annual revenue.
The SCoR2 inhibitor would enter a market transformed by GLP-1 success. It offers a different mechanism—blocking fat production rather than suppressing appetite—which could serve patients who don't respond to or can't tolerate GLP-1 drugs.