Dieses Interview fand in Englisch statt und ist hier inhaltlich wiedergegeben. Die deutsche Übersetzung findest du in einem parallelen Blogbeitrag mit dazugehörigen Podcast. Darin spreche ich beide Teile, die Fragen und Antworten.
Introduction of Prof. Dr. Claire Jacob
Nele: Today, I’m very happy to welcome Prof. Dr. Claire Jacob to an interview about her latest research outcome. Claire and her team understood a critical mechanism that enables the regeneration of myelin. Quite spectacular as this might result in a healing of disabilities caused by MS in the future.
Hello Claire, it’s a pleasure to have you on the podcast.
Claire: Hello Nele, thank you very much for inviting me to participate in this podcast. I am very happy to be online today with you and to answer your questions about our work related to MS.
Research focus and background
Nele: You have been doing research since 16 years on the development of myelin, damaged axons and how to regenerate them. What is your motivation for that? Was there any private relation to multiple sclerosis?
Claire: I have always been fascinated by the nervous system, how it works, how it can control our thinking process, our movements and the other functions of our body. This is why I chose to work on the nervous system and started by working on its development to understand how it functions. The nervous system is composed of neurons and glial cells, and among these glial cells are the myelinating cells, which are critical for the function of the nervous system.
Why did I start to work on myelinating cells? To be honest, it was by chance. I was a young researcher in San Francisco, in UCSF, working on chronic inflammation, and I decided to continue my research on the nervous system. I then looked for a research group who would welcome me as a new lab member and I found Prof. Ueli Suter at the ETH Zürich in Switzerland, who allowed me to join his research team.
Prof. Ueli Suter leads a research team that is renowned worldwide for their work on the cells that produce myelin in our body. This is how I started to work on myelinating cells. The story continues with an adverse event, which made me change my research focus to regeneration: 1 month after starting to work in the team of Ueli Suter in Switzerland, I had a traumatic spinal cord injury during a ski trip, which rendered me paraplegic.
After a stay at the hospital and a very long training with fantastic physiotherapists in Switzerland, I progressively recovered the lost functions. Although I did not recover 100% of the lost functions, I had a remarkable recovery with only some remaining sensory defects. When I was working hard with physiotherapists in rehabilitation, I made the promise to myself that if one day I can go back to the lab and do my research again, I will work on the regeneration of the nervous system.
I did manage to go back to the lab and when I could start my own lab, I specialized the work of my team on neuron and myelin regeneration after traumatic injuries and after lesions due to demyelinating diseases such as multiple sclerosis. This is the whole story!
The research team
Nele: Just to get an idea. How many people are roughly part of this research objective? Are we talking about ten people or more in the range of 100?
Claire: I have a very small research team, we are 7 at the moment. I recently moved my team from Switzerland to Germany and got our new lab going with experienced people only. Since the new lab is nicely running now, we will most likely grow soon with new PhD students and Postdocs, but I have to admit that I like very much to work with a small team. I find it more efficient and more satisfactory as group leader, since I can directly supervise the work of each lab member and we can make important decisions very fast this way.
Of course, now that we are on our way to set up clinical trials, more people from the medical, biostatistics and regulatory fields will be directly involved in our objective to make available a remyelination therapy for MS patients.
Remyelination in the peripheral nervous system versus the central nervous system
Nele: There is a difference in the healing of myelin between the peripheral nervous system and the central nervous system. Could you explain that in a simple way?
Claire: Thank you very much for this question Nele, I love to talk about this topic! It is a question that fascinates me and drives most of our research. I will do my best to answer in a simple way.
The peripheral nervous system and the central nervous system are very different, they are built by different cells. For instance, the cells that produce myelin in the peripheral nervous system are called Schwann cells and these cells react very differently to a lesion as compared to oligodendrocytes, which are the cells that produce myelin in the central nervous system. When a traumatic lesion occurs in the peripheral nervous system, Schwann cells that produce myelin around damaged axons get rid of their own myelin and change their shape and their identity to become repair cells that help the damaged axons to regrow. When axons have regrown, these Schwann cells wrap again the regenerated axons and remyelinate them. So, Schwann cells are very plastic cells: the same cell can change into a repair cell and change again into a remyelinating cell. For this reason, the peripheral nervous system can regenerate very well.
In contrast, the central nervous system does not regenerate efficiently after a traumatic lesion because the axons are not capable to regrow, partly due to the oligodendrocytes that block their regrowth. So, in the peripheral nervous system, Schwann cells help the axons to regrow, whereas in the central nervous system oligodendrocytes block axonal regrowth. This is one of the main reasons why the peripheral nervous system can regenerate better than the central nervous system.
However, here we are talking about traumatic injuries. If we talk about demyelinating lesions such as MS lesions, we cannot compare the central nervous system to the peripheral nervous system, because there is not a similar disease as in MS in the peripheral nervous system. There are some demyelinating diseases in the peripheral nervous system, but they are very different to MS.
In the case of MS, oligodendrocytes that produce myelin are attacked and die, which leads to a lesion. The main cells that are known to repair these lesions are the oligodendrocyte precursor cells. These cells are present in the central nervous system in adults and can become myelinating oligodendrocytes when there is the need to remyelinate, for example after a MS lesion.
The problem however is that remyelination after a MS lesion is never complete and becomes less and less efficient with age and as the disease progresses. Now, we know that one main reason for this decreased efficiency of remyelination is because oligodendrocyte precursor cells lose their ability to remyelinate with age. What we are trying to do in my lab is to push the oligodendrocyte precursor cells to remyelinate, even in aged individuals.
Regenerating myelin in the central nervous system
Nele: For MS patients the central nervous system is the most interesting one where lesions happen and might cause disabilities after a while. You achieved great results in experiments regenerating the myelin in the central nervous system of younger and older lab mice. How is that healing process working and what challenges did you have to overcome?
Claire: Since oligodendrocyte precursor cells progressively lose their ability to become myelinating cells in MS and during aging, we looked for a way to push them to produce myelin. For this, we went after the most essential mechanism that induces myelination: the transcriptional program of myelination that enables myelin components to be produced at the gene level. The challenge was to understand the full mechanism. It took us years of hard work to assemble the full process!
Nele: What will be the next steps for your research?
Claire: The work of my lab is focused on understanding the functions of a certain type of enzymes in the body that modulate the expression of our genes. These enzymes are called epigenetic factors or chromatin-remodeling enzymes. We will continue our research on these enzymes with the aim of utilizing them to improve the regeneration of axons and myelin. We think that understanding the function of these enzymes will provide a fantastic source of potential new strategies to control axonal regeneration and remyelination in the context of traumatic injuries or of degenerative diseases such as MS.
Nele: And what else is needed before there might be a working solution for healing damages in humans?
Claire: The next step for our recent discovery is to collect enough money to organize clinical trials to promote remyelination in MS patients. In addition, I am planning to set up another clinical study to promote remyelination after traumatic lesion in the peripheral nervous system.
Nele: Is there anything we as MS-patients can do to support your research?
Claire: Right now, what we need is funding for the clinical studies. MS patients who are in contact with potential donators or investors could help by making them aware of our research and of our financial needs for the clinical trials. The earlier we will have collected enough money, the sooner we will be able to test our potential treatment for MS patients.
Nele: Do you want to share anymore thoughts with the listeners?
Claire: Yes, I would like to thank all MS patients who have contacted me so far and showed their enthusiasm towards our work. This gives me a lot of energy to push this project forward. I also want to thank you very much Nele for organizing this podcast and giving me the occasion to talk about the next steps of our work.
Nele: Is it possible to stay tuned for your research activities?
Claire: Of course, you can always check my website at the University of Mainz to learn about our latest publications. In addition, in the section “News”, I always add a short text to summarize the key findings of our most important publications, as well as a link to the press release.
Nele: Thanks a lot for your time and especially for all your efforts during the last 16 years. I know that research can be quite frustrating as it takes many dead ends before finding a breakthrough milestone. And I do hope that you and your team will find a few more milestones down the road.
Claire: Thank you very much, Nele! Yes, we will continue our work to discover novel strategies to regenerate axons and myelin. This is what we love to do and even when the solution does not appear straight forward, we don’t give up!
Interesting links for follow-up
- News page
- Recent publication showing potential treatment for remyelination
- Press release in German
- Press release in English
Fundraising to start clinical trials
Claire and her team received a pre-approval from a new foundation focused on MS research for the funding of half of the clinical trials. But now they still need to find funding for the other half. So they created a fundraising account at the University of Mainz. Every small amount helps to finance the Myelin regeneration clinical study.
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