Mucopolysaccharidosis celebration Day

The impact of TIGEM research in the fight against MPSs
May 15, 2024
Mucopolysaccharidosis celebration Day

Nicola Brunetti-Pierri, PI at TIGEM, and Alba, one of the first patient treated with the gene therapy-based product developed at TIGEM

Mucopolysaccharidoses (MPSs) are a group of rare, inherited lysosomal storage disorders characterized by the body's inability to properly break down glycosaminoglycans (GAGs) due to deficiencies in specific lysosomal enzymes. This group includes several disorders, MPS III (Sanfilippo syndrome), and MPS VI (Maroteaux-Lamy syndrome), each associated with different enzyme deficiencies and varying symptoms. These can range from severe skeletal abnormalities to developmental delays, affecting multiple organ systems and leading to significant morbidity and early mortality.

Introduction to Mucopolysaccharidosis Type VI (MPS VI)

Mucopolysaccharidosis Type VI, also known as Maroteaux-Lamy syndrome, is a rare, autosomal recessive lysosomal storage disorder characterized by the body's inability to break down certain complex carbohydrates known as glycosaminoglycans (GAGs). This inability arises due to a deficiency in the lysosomal enzyme arylsulfatase B. The accumulation of GAGs in various tissues and organs leads to a range of symptoms including growth retardation, skeletal deformities, vision and hearing impairment, and cardiovascular issues.

Diagnosed through clinical observation and confirmed by genetic and enzyme assays, MPS VI is considered one of the more severe forms within the mucopolysaccharidoses spectrum. Traditional treatments have included supportive care, surgical interventions, and enzyme replacement therapy (ERT), which, while effective in mitigating some symptoms, does not fully address the underlying genetic fault.

TIGEM’s Groundbreaking Gene Therapy for MPS VI

TIGEM has been at the forefront of research in genetic diseases, particularly in developing innovative treatments for conditions like MPS VI. In a historic development, TIGEM initiated the world’s first in vivo gene therapy trial aimed at treating MPS VI. This groundbreaking approach, leveraging advanced genetic engineering techniques, represents a significant shift from conventional treatment strategies.

The Gene Therapy Approach

The gene therapy developed by TIGEM, and coordinated by Alberto Auricchio and Nicola Brunetti-Pierri, involves the use of a viral vector to deliver a healthy copy of the ARSB gene directly into the patient's bloodstream. This vector is engineered to target the liver, transforming it into a biofactory that continuously produces the arylsulfatase B enzyme, thereby correcting the enzyme deficiency at its source.

The decision to use an in vivo method, where the gene is delivered directly into the body, circumvents some of the challenges associated with ex vivo methods, such as the complexities of cell extraction and reintroduction, and potential complications related to stem cell transplantation.

Clinical Trials and Results

TIGEM's clinical trials commenced in 2017 with an initial cohort of nine patients receiving this novel treatment. The trials were designed to evaluate the safety and efficacy of the therapy, with a particular focus on the long-term expression of the enzyme and its clinical benefits. Results from these trials have been promising, especially in patients who received higher doses of the vector. These patients demonstrated sustained enzyme activity and clinical stability for periods extending up to four years—a testament to the potential of gene therapy as a transformative treatment for MPS VI.

Expanding Research to MPS IIIA

Beyond MPS VI, TIGEM is also advancing treatments for other types of MPS, notably MPS IIIA (Sanfilippo syndrome type A). This form of MPS, one of the most severe, currently lacks effective treatment options. TIGEM researchers are exploring the potential of repurposed drugs—medications already approved for other conditions—as a novel therapeutic strategy for MPS IIIA.

The repurposing effort at TIGEM by Elvira De Leonibus and Diego Medina involves two specific molecules that have shown promise in preclinical studies. These molecules are being investigated for their ability to enhance the elimination of toxic metabolites and improve neurological and behavioral symptoms in MPS IIIA patients. This approach underscores the importance of drug repurposing in rare diseases, offering a time-efficient and cost-effective route to new therapies by utilizing the existing safety profiles of approved drugs.

The Importance of Drug Repurposing in Rare Diseases

Drug repurposing is particularly crucial in the field of rare diseases, where research and development can be hindered by limited patient populations and high financial costs. By identifying new uses for existing medications, researchers can bypass much of the initial stages of drug development, accelerating the availability of therapies and reducing the investment risk.


TIGEM’s work with both pioneering gene therapy for MPS VI and innovative drug repurposing for MPS IIIA exemplifies cutting-edge research strategies in the fight against mucopolysaccharidoses. Our efforts not only offer hope to those suffering from these severe conditions but also set a precedent for addressing similar genetic diseases, highlighting the potential to fundamentally change the landscape of treatment for rare genetic disorders.