FTY720 for Treatment of Marfan Syndrome

NU2025-219

INVENTORS

Tsutomu Kume*
Can Tan

SHORT DESCRIPTION

This invention provides a novel use for FTY720, also known as Fingolimod, for the treatment and prevention of myxomatous degeneration of the mitral valve (MDMV) in Marfan syndrome.

BACKGROUND

Marfan syndrome, a genetic connective tissue disorder, frequently leads to MDMV, a severe cardiac complication causing valve prolapse, regurgitation, and potentially sudden death. This pathology stems from mutations in the FBN1 gene, resulting in disrupted extracellular matrix integrity, excessive TGF-beta signaling, inflammation, and impaired vascular and lymphatic function within the valve leaflets. Despite the significant morbidity and mortality associated with MDMV, its precise pathophysiology remains incompletely understood. Current medical management primarily focuses on symptomatic relief and surgical intervention once severe disease manifests, leaving a critical unmet need for pharmacological strategies to prevent or reverse the progressive valve degeneration.

ABSTRACT

FTY720 is an immunosuppressant approved for used in patients with relapsing forms of multiple sclerosis. Using the Fbn1 murine model of Marfan syndrome, Northwestern researchers discovered that FTY720 treatment rescued myxomatous mitral valve degeneration phenotypes. More specifically, mice that received FTY720 had diminished infiltration of immune cells, normalized leaflet morphology, reduced pathological proteoglycan accumulation, and improved collagen content compared to vehicle treated controls. Treated mice exhibited repaired cell-cell adhesion in both valve endothelial cells and lymphatic endothelial cells, and restored lymphatic drainage function. Thus, FTY720 is a promising new therapy for mitigating the underlying cellular and extracellular matrix pathologies associated with MDMV.

APPLICATIONS

Therapy for mitral valve disease in Marfan syndrome
Treatment for general myxomatous mitral valve disease beyond Marfan syndrome

ADVANTAGES

Non-surgical intervention – FTY720 provides a pharmacological approach for treating MDMV without the need for invasive mitral valve repair or replacement surgeries.
Targeted immunomodulation – FTY720 reduces immune cell infiltration in the mitral valve unlike current treatments such as beta-blockers or angiotensin receptor blockers.
Restoration of endothelial integrity – unlike existing therapies, FTY720 restores endothelial cell junctions to improve vascular barrier function and reduce valve degeneration
Improved lymphatic function – unlike existing therapies, FYY720 enhances lymphatic drainage, reducing interstitial fluid accumulation to mitigate valve pathology.
Established safety profile – As an FDA-approved drug, FTY720 has a well-documented safety profile to accelerate its repurposing for MDMV.

PUBLICATIONS

Tan et al. Lymphatic dysfunction and ZFP36 deficiency contribute to myxomatous valve degeneration in Marfan Syndrome mice. JCI (2026).

IP STATUS

A provisional patent has been filed.