Each month, we gather partners from the MAGIC project to discuss aspects in relation to gene therapies. Readers will learn who the people behind the MAGIC Project are, why we are committed to advancing gene therapies, and how our roles in MAGIC are crucial for achieving better health outcomes for people living with muscular dystrophies. This time, we are speaking with Ilaria Zito, molecular biologist and scientific coordinator of Parent Project aps Italy.

In brief words, please let us know who you are individually and on behalf of which project partner organization. 

My name is Ilaria Zito, a molecular biologist with a PhD in molecular genetics and a specialization in medical genetics. I’m Parent Project’s scientific coordinator and lead the Italian DMD/BMD Patient Registry. Together with Elena Poletti and Sara Massimi from the communication office, we represent Parent Project in the Magic Consortium.

Parent Project (PP) is an association of patients and parents of patients with Duchenne and Becker muscular dystrophy. Since 1996, PP aims to improve treatment, quality of life and long-term prospects of patients through research, education, training and awareness. Our scientific office supports research and manages the Italian DMD/BMD Patient Registry. The communication office promotes PP’s visibility and disseminates information on the condition, therapeutic strategies and clinical management.

Why are you participating in the MAGIC project? How can your perspectives complement the MAGIC project goal to accelerate the development of genetic therapies for muscular dystrophies? 

PP is involved in Work Package 8 (WP8): dissemination, communication and knowledge management. More specifically, PP’s role in the project is the dissemination of MAGIC findings to patient communities and the wide public in collaboration with other patient advocacy groups. The contribution that we can bring to the project comes from our almost-30-years long experience in the Duchenne and Becker field, that brought us to the consolidation of a strong community which embrace all stakeholders revolving around the disease, from patients and their families, to clinicians, scientists, industry partners and regulators, but also different Patient Associations around the globe.

As an example, last February Prof. Tedesco was invited to present MAGIC at our International Conference on Duchenne and Becker muscular dystrophy, involving around 700 people from over 30 countries, held every year in February in Rome.

What have been the current challenges regarding the development of genetic therapies for muscular dystrophies for you? 

As an association of patients and families with DMD/BMD we understand very well the burdens of people living with this disease knowing that currently, there is no cure. DMD and BMD are very complex pathologies involving all muscles of the body. Being a degenerative and progressive muscular disorder, there are many different associated complexities. Patients will lose their ambulation and subsequently upper limb mobility. The heart and all the respiratory muscles will eventually be involved. The use of corticosteroids, the actual standard of care, brings endocrine and nutritional issues, the need for assisted ventilation, and cardiac intervention, in what could be interpreted as a multi-organ disorder.

Experimental drugs such as gene therapy are being tested worldwide and although they aim to slow down disease progression, it cannot be considered a cure. A new genetic therapy proven to be more effective and safer is therefore highly needed for these patients.

The challenges associated with the gene therapies currently available include safety concerns associated with immune system reactions. Other issues are related to the existence of pre-existing antibodies, which may preclude dosing and the formation of specific antibodies after dosing which precludes a second administration.

Apart from these general aspects there are specific challenges associated with Duchenne muscular dystrophy that are due to the target tissue and the causative gene.

Reaching all muscles in the body at once is very challenging and the need for new vectors that may be more selective and efficacious in this regard is a big priority.

The dystrophin gene is the biggest one we have in our cells. It would not fit in any of the vectors currently used for gene therapy. Secondly, the spectrum of Duchenne causative mutations in this gene is extremely high and approaches like gene therapy and gene editing may potentially be applicable to all patients independently from their mutation. Several therapies have gone to the clinical stage but in most cases, they failed to reproduce the results obtained in the lab. It is therefore becoming urgent to improve the advanced approaches like gene therapy and gene editing on one side while developing new and more efficacious systems to screen these experimental drugs to advance only those that have a higher clinical potential.

What are the main outcomes (direct results) you expect from the project? 

We were thrilled to be involved in this ambitious project with a very high scientific relevance. We sincerely hope that with the scientists of the MAGIC consortium, extremely competent and with a high expertise and a long-standing experience in the neuromuscular field and/or in advanced therapies and technologies, we will be able to reach significant advancements in developing new advanced therapies that may prove more effective for the neuromuscular patients, or at least to start posing strong evidences and good data that will pave the way in this direction. Ultimately and hopefully making a real difference for all patients living with this condition.

What are the expected impacts on your organisation from participating in the project? 

Being at the forefront of what is moving in this fascinating and ever-changing field gives us the possibility of providing the most updated information to patients and their families and to communicate more effectively and directly. It also improves the relationships with other patients’ associations involved in the project allowing us to harmonize what we disseminate and how we do it.

Being in close contact with all the scientists of the consortium will add to our ever-growing network and will open new possibilities for connections among experts. For instance, during our International Annual Conference, new interesting research collaborations may arise.