A life dedicated to children

Maria Pia Cicalese works at SR-Tiget where she deals with gene therapy for genetic immunodeficiencies with the dream of changing the natural history of these diseases.

From research to the clinics, from laboratory to hospital ward and vice versa. With the aim of giving hope to girls and boys who are extremely vulnerable due to compromised immune systems.

And with the dream of changing the natural history of primitive immunodeficiencies, which greatly damage the body's own defenses from birth. A dream, that of Maria Pia Cicalese - researcher and pediatrician at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) - which is slowly becoming a reality thanks to the development of innovative therapeutic strategies that are tailor-made for young patients.

"We have developed the first gene therapy in the world based on patients’ stem cells: it is a drug approved for the treatment of Ada-Scid which is a rare immunodeficiency of genetic origin" she says in a voice that lets enthusiasm and passion shine.

Let's take a step back. When and how did you meet Fondazione Telethon?

"After graduating in medicine and surgery and specializing in paediatrics in Naples, I spent 7 months in London where I did clinical work and clinical research in the field of liver transplantation. There my interest in immunological diseases matured and my passion for immunology - the science that studies the immune system and that is still a quite unexplored field - was consolidated. When I returned to Italy, SR-Tiget - which is doing pioneering work in the field of gene therapy for various forms of primary immunodeficiency - was recruiting clinical researchers, and I jumped at the opportunity. It is 2010 and this is when I entered the Telethon family and begun to take my first steps in the field of gene therapy: at the Institute we work hard to make projects that seem futuristic become a reality."

So then you arrive at SR-Tiget, where work is already underway to develop gene therapy for Ada-Scid.

"Yes, this therapy is the result of over 20 years of research and when I arrived in Milan the first children involved in the clinical trial had already been treated between 2000 and 2010. In light of the excellent safety and efficacy results, we started to treat other children in compassionate use and I followed their therapeutic path. Shortly thereafter, GSK took over the production of the drug designed and produced at SR-Tiget to make it available on a large scale for as many patients as possible."

The Ospedale San Raffaele in Milan is the only center that is authorized to administer gene therapy for Ada-Scid. What did this result mean for you?

"An incredibly important goal. In fact, it represents the fulfillment of the Fondazione Telethon’s  mission: to advance research towards a cure. It is a life-saving treatment, a huge satisfaction. The feeling of having participated in a wonderful team effort spanning decades. For more than twenty years we have been working on this project that changed the history of medicine: the first drug based on stem cells modified ex vivo which marked an epochal turning point and the beginning of a new medicine. But also a new evolutionary stage for humanity."

Why?

"Because even a genetically written destiny, in some cases, can change".

How does the therapy actually work?

"Ada-Scid is a very rare genetic disease, due to a gene that - when defective - blocks the production of an enzyme called adenosine deaminase (Ada) that is essential to produce lymphocytes. Therefore, children born with Ada-Scid do not have a normal immune system and for them even the most common infection can be fatal. This is why it is called ‘bubble children's disease’: they are forced to live in a sterile and aseptic environment. The therapy consists of a single administration of stem cells modified with the correct gene: in other words, the stem cells are taken from the patient's bone marrow and are corrected in the laboratory (ex vivo). The normal version of the Ada gene is conveyed via a viral vector into the cells which, once reinfused into the same patient, produce a progeny of genetically corrected daughter cells."

Rewriting the natural history of genetic diseases, seeing a strategy designed in the laboratory arrive at the patient's bedside and offering hope: what does it mean?

"It is a dream coming true. It is proof that medicine is moving forward by leaps and bounds. The hope now is that this type of treatment can be extended to more and more genetic diseases and more quickly, being able to apply already existing technologies."

And for the future there are new challenges.

"Fondazione Telethon has undertaken a very important one. Ada-Scid risked returning being an orphan disease back again: being a rare disease, big pharma's interest in producing the cure ceased, as it was not profitable enough. After the initial alliance with GSK, the pharmaceutical company Orchard Therapeutics produced the drug. Last year, however, it announced its intention to disinvest in the field of primary immunodeficiencies. For us every single life counts, and we don't want children affected by Ada-Scid to be left alone without access to this therapeutic opportunity. This is why Telethon has decided to take charge of the marketing of this drug and it is an enormous emotion to think of the first child that we will soon treat with the drug produced and distributed by Telethon. This is why I want to underline the importance of networking, of keeping attention alive on rare genetic diseases and of financially supporting research. The future administration of this life-saving therapy ultimately depends on the availability of funds from Telethon and therefore depends on the generosity of our donors."

This article is a translation of the one originally published in italian by Fondazione Telethon.