Presidential Lecture Awardee: David Marsden Lecture Award | Congress 2026

So congratulations, Vincenzo, and thank you for the opportunity of talking to you again.

Prof. Vincenzo Bonifati: Thank you so much, Tiago. It's a great pleasure to talk to you and discuss about this award.

Prof. Tiago Outeiro: We talked last [00:01:00] year at the Congress. I had the pleasure of interviewing you, so I know a little bit about your background, but maybe we can talk a bit more about your career and what brought you to this nice recognition of the Society. And I know you've received multiple honors, including the MDS President's Distinguished Service Award and other major international awards.

So I want to start by asking, how do these recognitions shape your career and your networks and the way you connect to colleagues and maybe start even new projects?

Prof. Vincenzo Bonifati: First of all, let me say that this is a huge honor for me to receive this Marsden Award. I think for every neuroscientist or movement disorder researcher, this is a dream coming true to receive this award, so I'm very much honored and very happy for this.

Receiving awards recognition in international meetings is good for your network, of course, particularly for people [00:02:00] who are engaged in research like finding genes. This is a game that involves a lot of collaboration. Actually, by preparing the Marsden lecture, I was reviewing my collaboration networks, and I counted I think more than 100 different links with different centers across four continents, and it's actually impossible to list them all in a slide.

So this type of research is really revolving on a lot of collaboration with great clinicians, particularly, who are characterizing the families we are working on. It's an enormous boost to be recognized for your research because then other persons will get in touch and will try to establish additional links.

But apart from the awards, in my case, the first important discovery that was the DJ-1 gene, back to 2003, that was a huge boost for my career, for my network. After that publication, which came in [00:03:00] Science, there were a number of people who wanted to collaborate and send samples and send families to me.

And so I think perhaps the most important determinant of building a successful network is to have important papers and to also do important lectures at congresses. But also, of course, getting recognized with awards. Absolutely.

Prof. Tiago Outeiro: Now we'll come back to your science in a minute, but I want to just go back and tell our listeners how you started into the field. So you trained as a neurologist in Rome, and then you moved into human molecular genetics at Erasmus MC in Rotterdam, where you are a professor. So can you walk us through your journey and what drew you from clinical neurology into genetics?

Prof. Vincenzo Bonifati: Yeah. I studied medicine and graduated in Roma, in Italy, and then also got my certification in clinical neurology there and started working as a staff neurologist in the University of Roma, busy with diagnosis and therapy, especially of Parkinson's disease [00:04:00] patients. Also other movement disorders, but especially PD.

Then during my clinical work, I realized that there were so many patients with PD reporting a positive family history, which at that time, and we're talking of 35 years ago, it was not recognized. There were not many people who were really looking for families with Parkinson's disease.

The textbooks of neurology were saying PD is sporadic, it's not genetic, there is no family history. Actually, family history was considered an exclusion criteria for the clinical diagnosis of PD. So, in that context, I became so much fascinated by the fact that perhaps one in four of the patients had a family history of the disease, and I started to look for... examining those relatives. With my car, going around with my car in the weekends, in the villages surrounding Roma to see those people because they would not come to the university and there were no research grants to do that stuff at the time.

It was just like a hobby. And [00:05:00] then step by step, I collected a lot of families, which brought me to meetings, presenting posters about families with Parkinson's diseases from Italy, and that triggered the interest of other international people who were doing the same stuff. Which brought me in contact with Anita Harding, who was a pioneer in neurogenetics, as she was forming a European consortium on the genetics of PD in the mid-'90s.

That was my beginning into, let's say, a world-class type of research on genetics. And a few years later, my fascination for genetics was so strong that I wanted to move to a lab to really join the other part of the collaboration. So going in from the research on the clinical features, on the research on the DNA of those families, and that's why I moved to the Netherlands and my job changed, and I stayed there ever since.

I remained here. I did not go back anymore to the clinic.

Prof. Tiago Outeiro: And so you must have had several mentors along the way. So are there any names you want to [00:06:00] highlight and maybe tell us how they shaped the way you think about movement disorders today?

Prof. Vincenzo Bonifati: In Roma, my mentor was Giuseppe Meco, who was a professor of neurology responsible for the Parkinson's clinic. He taught me the clinical aspects of diagnosis and therapy of PD. And he was also a very good mentor in the neuropsychiatric aspects of neurology, which are very important.

Unfortunately, he died a few years ago prematurely, he would've been very happy to attend my Marsden Lecture nowadays. But then, when I moved to the Netherlands, I found two very important mentors, particularly Peter Huetink. He was the lab head of movement disorder research in Rotterdam.

And he has been perhaps the most important mentor for me scientifically. He introduced me to the human genetic research principles, particularly linkage analysis, the way to crack genetic code in large families, which was really instrumental for the big discoveries [00:07:00] of the last 20 years in genetics.

And also, after Peter moved to Amsterdam, Ben Oostra, who was the, let's say, the full professor in our department. He also was my last big mentor in my career. And I became associate professor and then full professor in the lab of Ben Oostra. And after his retirement I'm now the, let's say, the oldest one in the research group.

Prof. Tiago Outeiro: It's an amazing career and you mentioned big names, so I'm sure it was very exciting and stimulating to work with all those colleagues.

Prof. Vincenzo Bonifati: Peter Huetink was the person who was the senior author of the discovery of the tau gene, for example, as a cause of frontotemporal dementia as one of his achievements. The tau gene was actually found while I was already in collaboration with Peter from Italy as a neurologist. And Ben Oostra is the father of the Fragile X gene, one of the very first huge discoveries in molecular genetics of all time. I was in a great environment, very [00:08:00] stimulating environment.

Prof. Tiago Outeiro: Yeah. So clearly, that also helped you achieve all the great discoveries that you've achieved. And so I would like to touch briefly on those and ask you what would you say are the landmark discoveries in genetics that you've made over the years?

You already mentioned DJ-1, but I don't know if you want to highlight any others.

Prof. Vincenzo Bonifati: I think DJ-1 was the initial big finding, but my role there was still one of a young fellow. I was, kind of PhD student-equivalent, a research fellow in a group. I found DJ-1 with my hands, but it was still a younger role, a young fellow role.

A few years later, another important finding that came really with my lab already established, so with me as a main PI, was the discovery of the manganese transport disease caused by the mutation in a solute carrier gene, SLC30A10, which at the time was considered a zinc transporter.

And we identified it to be the [00:09:00] main manganese transporter in man. That was not only the solution of a rare disease but was the beginning of a new chapter in medicine, the metabolism of manganese in man. And now we know that there are at least three proteins, coded by different genes, which play different roles in the transport of manganese in different organs in the body.

This is a beautiful example of the power for discovery into human physiology of this rare form of genetics. So you find the cause of a human disease, a rare disease in most cases, and perhaps also a way to a therapy for those patients. But at the same time, you illuminate the physiology in man.

And this manganese transport disorder is a very good example of that. So I'm very proud of that discovery.

Years later, another one that I really am very dear to is the finding of a gene for an early-onset generalized dystonia form, which is the EIF2AK2. It's a kinase of the [00:10:00] eukaryotic initiation factor 2 alpha, which is an integral protein of the integrated stress response in man.

There were many hints already that dystonia is related to dysfunctional stress response, but this discovery really placed one of the central players in the pathway as a cause of human generalized dystonia. So really validating this hypothesis that dystonia, at least several of the generalized early-onset forms, perhaps if you like, the worst forms clinically, are an expression of an altered response to stress in cells.

This has, in my view, important implications also for the development of a possible therapy for this disease. And many genes, including DYT1, DYT6, even the sarcoglycan dystonia, impinge on this pathway one way or another. But our gene, the one that we found in my lab, is really at the center of the pathway. So in my view, this is also scientifically an important contribution.

There were [00:11:00] other discoveries, of course, of other genes. Each of them might be revealing another piece of the mosaic for Parkinson's disease or for dystonia. We are now working on another very nice finding in Parkinson's disease. It's a new gene, which is yet unpublished, and actually I plan to speak a little bit about this at the end of the Marsden Lecture. That's a gene I think that will be quite interesting for its implications in the pathogenesis of PD and the prevalence in the population.

Prof. Tiago Outeiro: I really admire your work because not only you do amazing studies on human genetics but you go also into the mechanisms, and your work has really brought some new insight into disease mechanisms. So that's, of course, very important so that we can try to one day treat these disorders better than what we are doing today.

So that's very impressive.

Prof. Vincenzo Bonifati: Thank you very much. Actually yeah, that's our goal, to find a therapy.

Prof. Tiago Outeiro: Now, leaving some [00:12:00] overview based on your experience to younger listeners. What advice can you give to younger investigators that are trying to enter the field of movement disorders and maybe even human genetics? Is there any advice you can give them for how they should shape their careers?

Prof. Vincenzo Bonifati: I think the future is really bright for genetics. So first of all, my message to young people is that if they want to enter into research in genetics for movement disorders it is still very good to do and I'm convinced that there will be many more genetic discoveries ahead.

So it's definitely a field on which a young researcher can invest. But of course there are others. What has been important for me in my career it's, I think, three things. One thing is to have good ideas, to see something perhaps before others that can be important and work on that.

To [00:13:00] work very hard. You must work very hard because it's difficult, to find important things is difficult. Obviously difficult. So you need to spend a lot of time and be persistent, be almost obsessed with something, to really achieve important results.

And also you need to have a bit of good luck, I think. That's also important in life because I know many very good geneticists who did not find a lot of genes and they are also... sometimes it's important to have to be at the right moment, the right time, at the same right spot, to have a good connection with clinicians, with the labs.

As I will tell in the lecture, every genetic discovery, at least for me, is a different story and has a different flavor. Sometimes it's the collaboration with a special clinician, at times with a special scientist. So you need to be capable of flexibility, let's say, also in your career.

 At least this is what has been, in [00:14:00] my view, the key to my success in research.

Perhaps the one important message also that I would like to transmit to the young generation is that you need to be perseverant. You need to work a long time. An important project is not a project of a month, of six months. It can last years.

Finding the DJ-1 took me two years of work, and nobody would guarantee at the beginning that I would find the gene. It could have been a total failure, right? So you have to work and be passionate about your work without being discouraged by failures and by the fact you have to repeat many times an experiment. I think in the current world with the bombing from internet and the news you get the perception of success coming easily from many angles of the world.

Everything happens, and it looks like, yeah, I also can do something and it's going to work and it's going to be successful. But unfortunately, the reality is not like that.

Prof. Tiago Outeiro: We [00:15:00] know science is not like that.

Prof. Vincenzo Bonifati: When we were PhD students there was no internet, so it was a complete different perception of the path to success, right?

Perhaps today everything is amplified, everything is accelerated, and this can lead to a misperception of the easy to be at the end of a project that's a success, right? At least, I perceive this, this challenge today.

Prof. Tiago Outeiro: Yeah, that they need to work hard and stay grounded and focused. That's very important. And now, if we look ahead, just for our final question, if we look 10 years from now, so imagine we are now in 2036, where do you think we will be in terms of the genetics of Parkinson's disease?

Prof. Vincenzo Bonifati: For Parkinson's particularly, in 10 years from now, most if not all of the genetic variants associated with the disease will be identified. GP2 is doing fantastic work to set the stage for this remaining part of the discovery by the design of case-control, right?

So [00:16:00] collecting a large number of cases and controls, looking for any type of variance, from rare to common, that can play a role in disease. I have no doubt that all this cataloging of variations that are associated with disease will be fully understood. In the meantime, also, again, the family-based approach will continue to produce results, and the family-based approach and genetic association studies will talk to each other and cross-fertilize their respective research space.

But the question will then be how to translate the genetic discovery into pathways for therapy and prevention. I think that will be the main research question in 10 years from now. And I hope by then we will also have already some validation of translational value of these genetic discoveries.

There are already many clinical trials running at the moment based on genetic discoveries, be it GBA or synuclein or LRRK2. Those are the three most [00:17:00] important. It is still hard to demonstrate disease-modifying effect. Yeah, that is difficult. That is also requiring a lot of time and a lot of efforts. But to me, there are no doubts that this is the way to the future. This is the way ahead for disease modification and ultimately disease prevention. Key question will be when you have to try to treat the subjects because when the disease is clinically evident, it might be too late, even if your target is correct, if the drug is correct.

It might be just too late to be clinically relevant. That is my worry. So research into early diagnosis and biomarkers of disease state before the clinical expression, I think will be very important in the next 10 years from now.

Prof. Tiago Outeiro: Thank you, Vincenzo. So definitely lots of important ideas that you left and also a teaser for all of us to go and listen to your lecture at the congress. Vincenzo, I want to thank you again for this opportunity, for talking to us and telling us a bit [00:18:00] about your career and where we are today with human genetics and all your important discoveries.

So thank you so much, Vincenzo.

Prof. Vincenzo Bonifati: Thank you very much, Tiago, and thank you to the listeners and see you all soon in Seoul.

Prof. Tiago Outeiro: Thank you. So we've interviewed Professor Bonifati on the occasion of his David Marsden Award in 2026. Thank you all for listening, and join us in our upcoming podcasts. [00:19:00]