Profile a Sanfilippo Researcher: Dr. Elvira De Leonibus

08 Dec 2021

Meet Dr. Elvira De Leonibus, a researcher at the Institute of Cellular Biology and Biochemistry (IBBC), National Research Council of Italy (CNR), and the Telethon Institute of Genetics and Medicine (TIGEM). She is working to understand symptoms in Sanfilippo, particularly the behavioural symptoms earlier in the disease course.

We are very grateful to all the researchers around the world working tirelessly to solve Sanfilippo. Below is a Q&A to get to know a little bit more about Dr. De Leonibus and her research.


1. Why did you become a scientist?

I enrolled in psychology because I had gotten to read Freud's books. For my 18th birthday, my classmates had given me all of his books as gifts. My dream was to "cure" children with autism issues. In those years, there were two dominant theories in psychology but none of these theories was satisfactory to me - I felt like the hardware was missing. So, I started to add to my courses of developmental psychology, courses that went more towards biology, such as the course of psychobiology of Prof. Stefano Puglisi-Allegra (La Sapienza University), who had been working for years on the regulation of the dopaminergic system by psychological stress. I then decided to do my thesis at the Faculty of Biology in the laboratory directed by Prof Andrea Mele and Prof Alberto Oliverio, to study the role of the dopaminergic system in subcortical circuits that regulate movement and memory. So, I did not choose to become a scientist, I simply liked to study and I was not satisfied with the information that was offered to me, I made my own ideas and I did not feel satisfied until I had tested them myself. 

2. How did you get involved in Sanfilippo research?

In 2007 I was offered to set up a laboratory for the study of animal behavior at the Telethon Institute of Genetics and Medicine (TIGEM), Fondazione Telethon. This involved running an animal behavior facility while continuing to work on my lines of research: the neurobiology of learning and memory in typical animals versus those that model human disease. I was only working on Parkinson's disease and had never heard of lysosomal storage diseases before. Being the head of an animal behavior facility is kind of like being an animal neurologist: a genetic change is presented, and you have to know what effect it has, you have to know the disease well. To do this, I always started by studying the clinical manifestations of these diseases. Among all the lysosomal diseases, Sanfilippo particularly struck me for two reasons: 1. It seemed to have two diseases in one syndrome, symptoms similar to autism (neurodevelopmental) in the initial phase and symptoms similar to neurodegenerative diseases of aging, such as dementia, in the final phase; 2. Children with Sanfilippo are born largely asymptomatic and remain so for around a year, they acquire all the behavioral skills, eating, walking, and talking and then gradually lose them. I had just had my little daughter at that time and I was experiencing the immense joy of her first words, but also the anxiety of reaching developmental milestones (her first words, her first steps). I put myself in the shoes of mothers of children with Sanfilippo, imagining the way they must feel as symptoms begin to emerge. I began to study models, but those available at the time did not seem satisfactory, because the disease was only studied in its final stage, the lysosomal stage, and no one had considered this initial phase. 

3. How would you describe your research to a non-scientist?

Our research starts with the motivation to understand the clinical, behavioral, or neurological symptoms in children with MPS-IIIA. We formulated the hypothesis that alteration of the dopaminergic system could be involved and that this initial stage was not due to lysosomal dysfunction. Dopamine is a neurotransmitter that regulates our behavior, in particular, our attention, cognition, and how much we move. I had been studying dopamine for years. I realized that dopaminergic drugs given to children with MPS-IIIA led to more side effects than beneficial consequences, so first I used an animal model to verify that there was a dopamine imbalance. Then we wanted to know when the dopaminergic system was deregulated, so we tracked back and found it began during embryonic life. This was an important discovery as we had clearly identified a neurodevelopmental defect in a disease that was previously thought to be only a neurodegenerative disorder. This discovery also has a broader impact on our understanding of autism. Nowadays, we understand that we can no longer talk about autism but need to talk of autisms, as the same behavioural syndrome can be due to different types of genetic changes and or different neurodevelopmental mechanisms. Thanks to the precious support of grants from Sanfilippo family foundations, we are currently studying the best pharmacological treatment for autistic-like symptoms, addressing the mechanism leading to the altered development of the dopaminergic system and also whether these same mechanisms are responsible for neurodegeneration manifesting in the late stages. 

4. What is your favourite part about your day in the lab?

At 7.30-8 am, the scientific meetings on the phone while I am stuck in the car on the ring road of Rome with Dr. Maria De Risi, post-doc in the lab, who is already in the laboratory at TIGEM and Prof Barbara Picconi, a close collaborator also stuck in the Rome traffic. These are the only moments when we are not disturbed and we can talk quietly. 

The daily interaction with the students, we have so many, especially the ones when we see the same light in their eyes for everything they learn and when they start to formulate hypotheses that they can't wait to verify. When we get good news of a grant accepted, a paper even just sent to journals (a great sense of liberation after years of work) and when we see data from experiments. The study part is also very nice and rewarding.

5. Share a turning point or defining moment in your work as a scientist.

Definitely my first research grant received from the Alzheimer's Association (USA) in 2010, which came on the very same day of a permanent position at the National Research Council (CNR) of Italy. In Italy there are few funds for research and in general there is no start-up money for researchers. Without this grant I would not have been able to start my independent lines of research. Also the synergy with Dr. Maria De Risi and the other members of my group have been fundamental for the study of Sanfilippo. There is a tendency in science to emphasize the work of the laboratory head, but the complexity of techniques, approaches, and diseases can be addressed only with the synergy of people from different backgrounds, and with a great working and scientific synergy. 

6. When you’re not busy with research, what do you like to do?

Research!!! All jokes aside, my children, my family and my friends with whom I enjoy spending time chatting, travelling and eating (another passion of mine). I like to knit, but even there, I'm not content to follow directions and the results are not as positive as in research, but I have never stopped in the face of criticism or difficulty and I just finished my latest cardigan for my daughter. However, I don't have any balance between private life and work, but for the simple fact that this is not a job for me. For the same reason, when I can, I choose collaborators with whom I would also go to dinner and even on vacation, for the same reason.