Rare diseases, Italian discovery of a possible cure for severe forms of alpha-sarcoglycanopathy

The San Martino and Gaslini di Genova study in 'Brain': from a drug already in use for 'Duchenne' a potential pharmacological strategy for treating the most acute forms of a rare genetic muscular dystrophy that still lacks a specific dedicated therapy

by Health Review

13 January 2026

4' min read

Translated by AI

Versione italiana

4' min read

Translated by AI

Versione italiana

Researchers at Irccs Ospedale Policlinico San Martino in Genoa and Irccs Istituto Giannina Gaslini have identified a potential pharmacological strategy for the treatment of the most severe forms of alpha-sarcoglycanopathy, a rare genetic muscular dystrophy that does not yet have a specific dedicated therapy, starting with a drug already in use for Duchenne muscular dystrophy. This is demonstrated by a study, the result of a collaboration between the two Institutes for Hospitalization and Treatment of Scientific Character, published in the journal Brain, which opens the way to a potential therapeutic intervention.

The disease

This is the first and largest multicentre study in the world, carried out on 16 patients, to focus on this rare form of muscular dystrophy characterised by early onset, in childhood, and rapid progression. A condition that significantly impairs the motor autonomy and quality of life of affected individuals and whose damage can often also involve the respiratory muscles. The researchers pointed out that the use of a reference therapy for Duchenne muscular dystrophy could represent the first form of treatment aimed at slowing down the disease's progression and improving the quality of life of patients with severe forms of alpha-sarcoglycanopathy, who until now have been orphans of an adequate cure. Moreover, thanks to biomarkers that can distinguish between severe and mild forms of the disease, the study has made it possible to identify patients who are more likely to respond to treatment. Currently, further research is underway to assess the possibility of translating these results into the clinical field, with the possibility of paving the way for therapeutic strategies offering concrete solutions.

The protagonists

The multicentre study led by San Martino in Genoa and Gaslini was coordinated by Lizzia Raffaghello, researcher and head of the Laboratory of Molecular Oncology and Angiogenesis, Irccs San Martino, and followed for the clinical part by Claudio Bruno, head of the Translational Centre for Myology and Neurodegenerative Pathologies at Gaslini, with the collaboration of Adriana Amaro, researcher at the Laboratory of Gene Expression Regulation, Irccs San Martino, for genomic and bioinformatic analyses. The research involved researchers and clinicians from nine Italian, one French and one German centres and collected data from 16 patients with alpha-sarcoglycanopathy. The work focused on the role of inflammation in disease progression and how this could be switched off by corticosteroid therapy, similar to what is already done in Duchenne muscular dystrophy.

'Alpha-sarcoglycanopathy is a rare muscular dystrophy, with recessive genetic transmission, that belongs to a very heterogeneous group of muscular dystrophies involving the pelvic and scapular girdle muscles. Specifically, alpha-sarcoglycanopathy is caused by a defect in the alpha-type sarcoglycan protein, which is found in the membrane of the muscle cell and whose role is to give it stability and protection against damage that develops during muscle contraction. When this protein is missing, the membrane becomes fragile and it takes little to break it and activate the immune system, triggering inflammation,' he continues.

The Studio

'This study represents the first characterisation from a molecular point of view of what are the inflammatory processes in alpha-sarcoglycanopathy,' emphasises Raffaghello, research coordinator. 'In dystrophies, inflammation is an important cause underlying the disease's progression. Despite this, until now it has not been studied in relation to sarcoglycanopathies, as has been done for Duchenne muscular dystrophy. Our work has attempted to fill this gap by conducting the largest multicentre study on the role of inflammation in alpha-sarcoglycanopathy,' he points out. First, the 16 patients, previously classified into severe or mild forms of the disease based on alpha-sarcoglycan protein expression, underwent sequencing and analysis of muscle biopsies. This analysis showed that the severe forms of the disease have different gene expression from the mild cases. In severe cases, there is a greater activation of genes associated with inflammatory processes and, specifically, a greater presence of pro-inflammatory lymphocytes and monocytes linked to the near-absence of alpha-sarcoglycan,' Raffaghello reports. 'This characterisation therefore made it possible to compare with other muscular dystrophies to understand whether severe and mild cases could have a gene activation similar to that of patients with other neuromuscular diseases,' he adds. Surprisingly, it turned out that patients with a mild form of alpha-sarcoglycanopathy show a genetic signature comparable to that of patients without the disease, while severe manifestations are very similar to Duchenne muscular dystrophy. This suggests the possibility of considering an anti-inflammatory therapy for severe forms of alpha-sarcoglycanopathy similar to that of Duchenne, based on corticosteroids, which could help slow down disease progression. In addition, having identified biomarkers that distinguish severe from mild forms also makes it possible to better tailor therapies and suggest treatment only to patients with severe forms and exclude those with moderate manifestations, who would not benefit from it'.

A first step

"It is a dystrophy on which few studies have been carried out and which to date has no specific treatment protocol. There are only rehabilitation treatments aimed at avoiding the most serious damage associated with the disease, but these do not cure the disease. Three clinical trials have been conducted, all completed to date, which have studied how to limit the disease's progression by inserting the alpha-sarcoglycan gene into adenoviral vectors to reintroduce the missing gene and restore it, but complete data on efficacy and safety are still lacking,' says Bruno. 'Our work therefore represents the first step towards a possible pharmacological treatment of alpha-sarcoglycanopathy, which could slow down the disease progression of patients, very often children. The close collaboration between clinicians, cell and molecular biologists and bioinformaticians as well as the willingness of all collaborating centres to provide valuable biopsy material was crucial to achieve this important result,' Raffaghello concludes.