This important research, supported by our association Progetto Mitofusina 2 ETS, was conducted by researchers from the “Centro Dino Ferrari” of the University of Milan and the Policlinico di Milano, in collaboration with IRCCS E. Medea in Bosisio Parini (Lecco). The study was coordinated by Prof. Stefania Paola Corti and Dr. Elena Abati of the Neural Stem Cell Laboratory of the “Centro Dino Ferrari”.

For Progetto Mitofusina 2 ETS, this publication represents a particularly significant achievement, as it is part of the research pathway that our association has been supporting with continuity and commitment, with the aim of contributing to a better understanding of CMT2A and to the development of useful tools for future clinical studies. We therefore thank our researchers for their constant dedication and congratulate them on the excellent results achieved.

THE STUDY

The main discovery of this study is a biomarker measurable in the blood, capable of detecting damage to the peripheral nerves in Charcot-Marie-Tooth disease type 2A (CMT2A). For the first time, a study systematically evaluates serum biomarkers in a cohort of patients affected by CMT2A, the most common axonal form of hereditary peripheral neuropathy, caused by mutations in the Mitofusin 2 gene (MFN2).

CMT2A is a rare neuromuscular disease that causes progressive degeneration of nerve fibers, resulting in muscle weakness, loss of sensation and walking difficulties. To date, no approved therapy exists and, until this study, objective tools to measure disease progression or assess the effectiveness of new treatments were lacking.

The research, coordinated by Prof. Stefania Paola Corti and Elena Abati, researcher at the Neural Stem Cell Laboratory of the “Centro Dino Ferrari”, measured four candidate molecules in the blood of 15 patients with CMT2A, 10 healthy controls and 16 patients affected by other neuromuscular diseases: Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA) type 3. The same biomarkers were also evaluated in a transgenic animal model of CMT2A, genetically modified to reproduce the human disease.

“Neurofilament light chain — NfL — was found to be elevated in the blood of patients with CMT2A compared with healthy controls, and this finding was also confirmed in affected animals,” explains Elena Abati, first author of the study. “NfL levels in patients with CMT2A were intermediate between those observed in patients with ALS and SMA3: this suggests that the biomarker may help distinguish CMT2A from clinically similar conditions through a simple blood test.”

The study identified a second promising biomarker: FGF21 (Fibroblast Growth Factor 21), a protein that increases when cells are under mitochondrial stress, meaning an alteration in the functioning of mitochondria, the cell’s “powerhouses”. This biomarker was also found to be significantly elevated in patients with CMT2A. This finding is consistent with the mechanism underlying the disease: CMT2A is caused by mutations in the MFN2 gene, which is essential for proper mitochondrial function. Alterations in this gene impair the fusion and transport of mitochondria within nerve cells, contributing to the progressive damage of peripheral nerves typical of the disease.

“Having validated biomarkers in the blood means being able to objectively measure the effect of new therapies — including the gene therapy approaches we are developing — without resorting to invasive procedures,” emphasizes Federica Rizzo, co-author of the study. “This study is a fundamental step towards more effective and accessible clinical trials for patients with CMT2A.”

The study also describes three new variants of the MFN2 gene (p.Ile88Val, p.Lys243Met, p.Leu733Pro), never previously reported in the literature, further expanding knowledge of the genetic heterogeneity of CMT2A.

The research was made possible thanks to the central financial support of Progetto Mitofusina 2 Onlus, whose contribution was essential to advancing this line of research. A fundamental contribution also came from patients affiliated with ACMT-Rete, the Italian association for CMT, who voluntarily took part in the study after providing written informed consent, donating biological samples that were essential for biomarker validation.

REFERENCES

SCIENTIFIC PUBLICATION

Abati E., Saccomanno D., Alberti C., Anastasia A., Gagliardi D., Ferri E., Arosio B., D’Angelo G., Cima R., Bassi M.T., Oldoni S., Comi G.P., Rizzo F., Corti S.P.
Investigating the role of serum NfL, FGF21, NCAM1 and GDF15 as disease biomarkers for Charcot-Marie-Tooth type 2A.
Scientific Reports, 16, Article number 16259, 2026. DOI: 10.1038/s41598-026-49537-5.