A pioneering gene therapy to treat diseases associated with endoplasmic reticulum stress
The University of Barcelona (UB) has received a Producte grant of 150,000 euros from AGAUR to develop a new gene therapy aimed at treating endoplasmic reticulum (ER) stress, a key cellular dysfunction involved in multiple diseases, ranging from metabolic disorders such as diabetes to cancer and various rare genetic conditions. The project is led by Dr. Antonio Zorzano, Professor in the Department of Biochemistry and Molecular Biomedicine at the UB’s Faculty of Biology and a member of IRB Barcelona. The team also includes Dr. Kevin Aguilar, participating as an entrepreneurial scientist, and Dr. Deborah Naon as the scientific lead of the project.
The first therapeutic target of this innovative strategy is alpha-1 antitrypsin deficiency (AATD), a rare hereditary disease with no effective treatment that affects one in every 2,000–5,000 births and accounts for 2–3% of chronic obstructive pulmonary disease (COPD) cases.
AATD is caused by a mutation in the alpha-1 antitrypsin (α1AT) gene, which leads to the accumulation of this protein in the liver, triggering endoplasmic reticulum stress —an organelle found inside human cells— and causing liver and lung damage. Current therapies supply α1AT protein to the lungs through intravenous infusion, but they do not resolve liver damage or the underlying cellular stress that drives the disease. “Our goal is to develop a comprehensive therapy that addresses both the pulmonary and hepatic symptoms of AATD, improving the clinical outcomes of patients affected by this condition,” explains Dr. Zorzano.
“This represents a paradigm shift, as this gene therapy does not aim to replace a gene, but instead acts through a therapeutic mechanism that directly targets endoplasmic reticulum stress and restores communication between cellular organelles,” the UB professor highlights.
Preliminary data from both mouse models and cellular models of the disease indicate that the therapy could reduce protein accumulation in liver cells and improve the overall clinical manifestations.
Potential impact on many other diseases
Given the large number of diseases associated with endoplasmic reticulum stress, this therapeutic strategy could be extended to a wide range of conditions that share this mechanism—either as a standalone treatment or in combination with others—particularly those that currently lack effective therapies.
Thanks to the funding received through the Producte grant, the researchers will be able to validate this new strategy in an advanced mouse model of AATD to demonstrate its effectiveness and compare it with existing solutions. They will also analyse its potential in other diseases linked to endoplasmic reticulum stress, as well as improvements in the delivery systems of the future drug.
Contribution to the Sustainable Development Goals
The project contributes to the Sustainable Development Goals (SDGs) of the 2030 Agenda by aiming to improve quality of life in rare diseases without effective treatments (SDG 3, Good Health and Well-being), promoting innovation in gene therapy and biomedicine (SDG 9, Industry, Innovation and Infrastructure), fostering job creation in biotechnology and reducing the economic burden on healthcare systems (SDG 8, Decent Work and Economic Growth), prioritising ethical preclinical models and sustainable research practices (SDG 12, Responsible Consumption and Production), and promoting collaboration among researchers, clinicians, and policymakers to accelerate the arrival of new therapies to society (SDG 17, Partnerships for the Goals).
The project, with grant number 2025 PROD 00173, forms part of the Knowledge Industry call under the “Producte Grants aimed at obtaining prototypes and at the valorisation and transfer of research results generated by research teams in Catalonia.”
Photo caption: The image shows a liver cell displaying a normal phenotype in the presence of the new compound, despite expressing the mutated protein that is the main cause of AATD.