Alzheimer’s Drug Preserves Memory and Brain Function in Mice
New drug inhibits sEH, reducing inflammation and preserving memory in Alzheimer’s mouse models.
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A research team from the University of Barcelona has developed a new therapeutic compound that shows potential to reduce neuroinflammation and preserve brain function in mouse models of Alzheimer’s disease. The drug candidate, which inhibits the enzyme soluble epoxide hydrolase (sEH), demonstrated neuroprotective and anti-inflammatory effects in two different murine models, according to findings published in ACS Pharmacology & Translational Science.
Soluble epoxide hydrolase (sEH)
An enzyme involved in the breakdown of lipid molecules that regulate inflammation and pain. Inhibiting sEH increases anti-inflammatory compounds in the brain and may help reduce neuroinflammation linked to Alzheimer’s disease.
Neuroinflammation
A chronic inflammatory response within the brain often linked to neurodegenerative diseases such as Alzheimer’s. It involves activation of immune cells in the brain and the release of pro-inflammatory molecules.The work was led by Mercè Pallàs and Santiago Vázquez from the Faculty of Pharmacy and Food Sciences at the University of Barcelona. Researchers from several institutions including the Institute of Neurosciences (UBNeuro), the Institute of Biomedicine of the University of Barcelona (IBUB) and international collaborators from the University of Bonn were involved.
Targeting neuroinflammation in Alzheimer’s
Alzheimer’s disease is the leading cause of dementia, affecting over 800,000 people in Spain alone. Current treatments offer only modest symptomatic relief and are largely ineffective at halting disease progression. While many experimental approaches have focused on removing beta-amyloid plaques from the brain, recent evidence suggests that chronic inflammation may also play a central role in the disease.
The team’s compound targets sEH, a regulatory enzyme involved in inflammatory processes. By blocking sEH, levels of endogenous anti-inflammatory molecules known as epoxyeicosatrienoic acids (EETs) are increased. These molecules are thought to support neuronal health and improve cerebral blood flow, which is often impaired in individuals with Alzheimer’s.
Epoxyeicosatrienoic acids (EETs)
Bioactive lipid compounds with anti-inflammatory and vasodilatory properties. EETs support blood flow in the brain and have been shown to protect neurons in preclinical models of neurological disease.Memory and neuronal function preserved in treated mice
The researchers tested the compound in two distinct mouse models of Alzheimer’s disease. Treated animals showed improvements in spatial and working memory, alongside preservation of the brain’s neural network. These outcomes were associated with reductions in markers of inflammation and increased expression of protective immune signals.
Unlike traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, the new compound appeared to influence several inflammatory pathways simultaneously. This multi-target mechanism may be key to its observed efficacy in modifying disease pathology and symptoms.
In addition, the treatment's benefits appeared to persist even after it was discontinued. One month after stopping the drug, cognitive improvements and neuronal integrity were still detectable in the mice. These findings suggest that the drug may go beyond symptom management and influence the underlying disease process.
Next steps toward clinical development
Although the results are promising, the compound remains in early stages of development. The road to clinical use involves further testing, including toxicity studies and clinical trials to evaluate safety and efficacy in humans. The compound’s patent has been licensed to a pharmaceutical company in the United States, which will lead its progression through preclinical and clinical phases.
Members of the University of Barcelona team will continue to advise on the compound’s development as expert consultants, ensuring scientific continuity as the drug moves closer to potential clinical use.
Reference: Jarne-Ferrer J, Sánchez J, Codony S, et al. Novel soluble epoxide hydrolase inhibitor: toward regulatory preclinical studies. ACS Pharmacol Transl Sci. 2025;8(2):533-542. doi: 10.1021/acsptsci.4c00629
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