Ticino at the forefront of medical research

Maurizio Molinari gives the first in a series of articles in collaboration with USI (Università della Svizzera italiana) for Ticino Welcome magazine. He is group leader at the IRB (Institute for Biomedical Research) at Università della Svizzera italiana in Bellinzona.

Who is Maurizio Molinari and how did he arrive at the IRB?

I was born in Lugano, 50 years ago. After high school I chose to study in Zurich at the ETH, where I graduated and completed a PhD in biochemistry. I then was given the opportunity to go to the University of Padua, Italy, as a post-doctoral research at the Faculty of Biomedical Sciences. I have always been interested in biomedicine, and in Padua, I was part of the research team of Prof. Montecucco that discovered the consequences of the cellular infections caused by toxins such as tetanus and botulin. I eventually returned to Zurich at the ETH and, after a couple of years, was contacted by Antonio Lanzavecchia and Marco Baggiolini (at that time president of the USI), who asked me if I was interested in working at a new institute that was being created in Ticino.

Therefore, you were among the founders of the IRB…

The main architect of the IRB is Giorgio Noseda, and the Institute was created around the research groups of Antonio Lanzavecchia and Federica Sallusto (both hailing from the Basel Institute of Immunology), and of Mariagrazia Ugoccioni and Marcus Thelen (both hailing from the Theordor Kocher Institute in Berne). Therefore, I was de facto the first recruited Group leader since the foundation of the Institute, and I started working in September 2000, on the day the IRB was inaugurated. Since 2008, I am Associate Professor at the EPFL in Lausanne.

Have you always been active as a researcher or have you also had experience in the industry as well?

I have always conducted basic research. In my group at the IRB, we are all cell biologists, and what we want to study is how cells exert their fundamental activities, namely the production of proteins. The problems in producing proteins are responsible for very serious diseases ranging from cancer to rare diseases, which interest us mostly and that are one of the main lines of research conducted in our lab.

What is a rare disease?

Firstly, the term “rare” needs clarification, as it is slightly misleading. In fact, for certain diseases we know of very few people affected (in some cases, 1-2 patients worldwide), whereas for others we count larger numbers (cystic fibrosis, for example, affects around 1000 individuals in Switzerland alone). A study commissioned by the Swiss Federal Council estimates that the number of individuals affected by a rare disease in Switzerland ranges from a minimum of 2.2% to a maximum of 12.3% of the population. In Ticino, this translates into a minimum of 7.700 to a maximum of 43.000 individuals (source).

Many rare diseases are caused by DNA mutations, leading to the production of damaged proteins that can no longer function properly, thus accumulating in our cells and poisoning them. Many rare diseases affect children, whereas others occur in adults or aged persons. A detailed study of all rare diseases is unreasonable (to date, about 8.000 are known and five new ones are discovered every week on average), therefore it is important to find a way to group them by common characteristics that can allow for the development of treatments applicable to a range of diseases.

Tell us more about your article that was recently published in Nature Cell Biology.

At the end of 2016, we published our discovery of a new form of autophagy, a phenomenon of the human cell, originally discovered 50 years ago and highlighted in the 2016 Nobel Prize for Medicine. Autophagy causes cells to ‘eat themselves’, to recycle old components (for example old proteins) and produce new ones. The distinctive feature of the new form of autophagy that we describe in our study is that it does not aim at recycling old material; instead, it destroys parts for the cell containing harmful elements. We named this new type of autophagy recover-phagy, because it allows cells to recover from a condition of stress caused by the accumulation of modified proteins, by ‘eating’ (phagy) the toxic aggregates. In fact, certain rare diseases are caused precisely by the inability of the cells of our bodies to remove such accumulations and drugs enhancing autophagy have entered the clinical testing phase.

What is being done in Ticino to assist families ‘afflicted’ by rare diseases?

In Ticino and in Switzerland I believe that we could do much more in providing adequate assistance to families concerned with rare diseases, in terms of obtaining early diagnosis, accessing data on diseases in the region and the related existing therapies, and helping to manage social, professional and administrative issues. The Federal Council, at the end of 2014, issued a National Rare Disease Policy which analyses the current situation in Switzerland and sets rapidly achievable targets to bridge the gap with neighbouring countries, who in certain areas are faring better. Only recently, with the creation of the Piattaforma Malattie Rare Svizzera italiana (Platform for Rare Diseases in the Italian-speaking part of Switzerland), at the end of 2016, Ticino has managed to enter the said Federal National Plan for Rare Diseases.

An IRB initiative, therefore…

In 2015, I asked myself how many children were affected by a rare disease here in Ticino. I then asked the same question to a number of pediatricians, who however could provide me only with indicative numbers. In fact, in Ticino there is no specific register for collecting data on patients affected by these diseases. Together with Prof. Ramelli of the EOC we had a series of informal meetings with physicians, researchers, patient association representatives, and politicians – from Ticino and other regions as well.

These meetings eventually became more structured and, thanks to the support of Prof. Dr. Mario Bianchetti, Dean of the Faculty of Biomedical Sciences at USI, and especially of Dr. Fabrizio Barazzoni, Medical Chief Officer at EOC, in October 2016 our initiative saw the light with the creation of the said Piattaforma Malattie Rare Svizzera italiana. Current participants in the Platform are EOC, USI, SUPSI, Cardiocentro Ticino, Institute of Oncology Research (IOR), Neurocentro della Svizzera Italiana (NSI), Association for Rare Genetic Diseases, Hildebrand Clinic, IRB, Istituto delle Assicurazioni Sociali and the Cantonal Chief physician.

This interview was originally published in Ticino Welcome magazine, March-May 2017, p.72-73