The University of Barcelona collaborates in a public-private consortium to develop a new therapy for Marfan syndrome
Marfan syndrome is a rare genetic disorder that affects connective tissue and alters the functioning of organs that require elasticity, such as the skin, lungs, eyes and major blood vessels like the aorta. The most serious manifestation is the abnormal dilation of the aortic wall (aneurysm) accompanied by the possible rupture of the aorta (dissection), a life-threatening complication for which there is currently no effective pharmacological treatment.
In this context, researchers from the University of Barcelona (UB) are participating in a public-private consortium led by the company Medibiofarma with the aim of developing an innovative therapy designed to prevent, or at least attenuate, the aortic damage associated with this syndrome. The initiative, which also includes the participation of the University of Santiago de Compostela, aims to advance a promising drug to phase II clinical trials in patients.
“This project aims to promote the development of MBF-118, a novel drug discovered, developed and patented by Medibiofarma, as a therapy for Marfan syndrome and, by extension, for other aortopathies, both genetic and non-genetic, thereby significantly improving patients’ quality of life,” explains Gustavo Egea, Professor in the Department of Biomedicine at the Faculty of Medicine and Health Sciences, who leads UB’s participation in the project.
A promising mechanism of action
Currently, there are no pharmacological therapies capable of effectively stopping or delaying the aortic damage associated with Marfan syndrome. The main therapeutic option is surgical repair of aortic dissection or rupture, which is not without risks. In this scenario, the compound MBF-118 emerges as a promising pharmacological alternative thanks to its ability to selectively and controllably activate the PPARγ receptor, whose expression is markedly reduced in the Marfan aorta.
This receptor is mainly known for its role in fatty acid and glucose metabolism, but several studies have shown that it also plays a relevant role in the vascular system. According to Egea, through this mechanism of action, the drug could “help restore balance in aortic tissue and exert beneficial effects on the integrity and functionality of the aortic wall, cellular signalling and probably also on blood flow, thus reinforcing its potential as a new therapeutic option.”
Positive preclinical and clinical results
The compound MBF-118 has already passed several stages of pharmaceutical development. Data obtained to date —both in animal models and in a proof-of-concept study in patients with Crohn’s disease— indicate that the drug is safe and well tolerated in humans. Moreover, it shows adequate absorption and reaches sufficient and sustained blood concentrations over time to induce the desired therapeutic effects.
In this context, the project will make it possible to evaluate the therapeutic potential of MBF-118 in an animal model that closely represents the clinical progression of Marfan syndrome in patients, as well as to carry out the toxicological studies required to meet the regulatory requirements for future long-term clinical trials in patients. “This work will help validate the compound’s effect in the prevention/attenuation of aortic aneurysms and dissections and their pathophysiology,” highlights Egea, whose research group brings extensive experience in studying the pathological mechanisms of aortic diseases.
In addition, new formulations of the compound will be developed throughout the project. “This will help patients follow the treatment more easily, with particular consideration for paediatric patients with Marfan syndrome,” adds the researcher.
Achieving these objectives will facilitate the designation of MBF-118 as an orphan drug for this genetic disorder. Orphan drugs are intended for the treatment of rare diseases and benefit from regulatory and financial incentives that support their development. This designation will accelerate the launch of a phase II clinical trial with MBF-118 in patients with this disease.
The project, entitled “Research and development of a new therapy for the treatment of Marfan Syndrome (Marfan-PPARg)”, has a duration of three years and reference number CPP2024-011398. The University of Barcelona has obtained funding of 267,550 euros under the 2024 call for public-private collaboration projects, funded by the Ministry of Science, Innovation and Universities, the State Research Agency and FEDER funds.
Caption: Members of the Vascular Cell Biology group (UB-IDIBAPS).
