Selected by Chance: An Interview with Ralf Reilmann

Dr. Ralf Reilmann

Dr. Ralf Reilmann

VITAL SIGNS

CURRENT POSITION: Founding Director of the George Huntington Institut, Münster, Germany. Member, HD Insights Editorial Board.

EDUCATION: MD, Westfälische WilhelmsUniversität Münster (University of Münster), Münster, Germany; Postdoctoral Research Fellowship, Columbia University, New York, NY.

HOBBIES: Jogging, traveling, and discovering the world through the eyes of his seven-year-old daughter. Dr. Ralf Reilmann

HD INSIGHTS: Dr. Reilmann, you recently founded the George Huntington Institute in Münster, Germany. What is the vision of the Institute?

REILMANN: We want to be a dynamic factor in the development and translation of approaches to treating HD. We want to contribute to finding a cure, while providing the best possible, research-based care for patients and their relatives. We also want to foster international collaboration and friendship among HD researchers, and could potentially be a harbor for those who find it problematic to survive in their current settings doing HD research. We also want to directly connect the people in this region to our mission. The institute gives us the opportunity to educate people, including patients, about what’s going on in research, and gives them the opportunity to participate in trials. With a critical mass of people working together— physicians, neuropsychologists, study nurses, researchers— it’s a much more stimulating environment. Development in HD is by no means driven by any one person. It’s a continual pleasure to see what collaboration and international research support can bring about, and I’m glad to be a part of it. Unfortunately, neurodegenerative diseases like HD are very badly reimbursed in the national health schemes of Germany and other European countries, and it’s quite difficult to find support for HD research and care in a large hospital setting. So, the impetus for our formation was to create an infrastructure that allows us to offer Huntington’s patients the optimum level of care, and support our research efforts.

REILMANN: Patients are now coming to us from many hundreds of kilometers away. We have space for different physicians to see patients, with nicely equipped rooms, a big waiting area, a kitchen, and a conference room. We have a lot more resources for our work on HD. And we have the potential to grow: we have planned to pursue the founding of an external large animal facility, to support initiatives like the transgenic pig project we have just started with funding from CHDI, which would give us the opportunity to do research much more dynamically.

HD INSIGHTS: How did you become interested in HD?

REILMANN: Actually, I was drawn into HD research by chance. While I was completing my preclinical studies in medical school, I decided that I wanted to do a thesis in neurology with two of my friends. Our topic was assessment of neurotransmitters in epilepsy, HD, and PD, and my friends insisted that we draw lots. I drew HD! At first, I was disappointed, because I had attended a really interesting course on epilepsy by one of our professors. But when I travelled to Düsseldorf to work with Dr. Herwig Lange, who founded the first inpatient HD ward in Germany, I became fascinated by HD. While I was still analyzing my thesis research, the HD gene was discovered. With a grant from a German scholarship foundation, I joined a lab in Germany that was part of the international team that had discovered the gene. After medical school I went to Queen’s Square in London and studied with David Marsden, the founder of the Movement Disorder Society, who got me interested in quantifying movement disorders more objectively. He urged me to go to Columbia University in New York to pursue my interest, so after two years of neurology residency, I went to New York with a grant from the German government. I could have worked on the quantitative motor (Q-motor) idea in other diseases, but Karen Marder, who ran this big HD center at Columbia, and Carol Moskowitz, dragged me into HD again. I began to validate my Q-motor idea in HD patients. When I returned to Europe in 2001, Bernhard Landwehrmeyer asked me to join the European HD Network initiative and guide the motor working group. I have taken up the project of developing the UHDRS-TMS online certification program, with videos and to develop the Q-motor assessments. I suppose that really gave me the impetus to found the George Huntington Institute and pursue my way, totally focused on HD.

HD INSIGHTS: Could you comment on challenges and improvements in HD research?

REILMANN: The dream I had when I went into HD research is still driving me: to find a cure for HD. We must find a treatment that hits the causal mechanism of this disease. On top of that, we have the opportunity to introduce this treatment in the premanifest stage. This is something very new in medicine: currently, you need to show a benefit to the patient to get regulatory approval to use new drugs. We are challenged to leave this paradigm, because we have the potential to treat people before they become ill. The big studies like TRACK-HD1 and PREDICT-HD2 have quite successfully shown that we do have clinical trial endpoints that work in symptomatic HD, and we have gained a better understanding of how endpoints such as the Q-motor and UHDRS work even in premanifest stages. We have also learned how imaging can contribute to evaluating novel therapies, and we have opportunities to develop novel endpoints that will give us the chance to move therapies into the premanifest domain. This, I think, is the most exciting opportunity we have, above and beyond even HD: we could potentially do clinical trials that would allow us to introduce new therapies before people become sick. The HD community gives us the support of thousands of people who are keen to be involved in research. I think there is great potential for successfully completing clinical development programs and delivering novel therapies to HD patients.

HD INSIGHTS: You are involved in a number of HD clinical trials. Which do you find most promising?

REILMANN: I think a couple of promising compounds are around the corner. The HD field has attracted a lot of recent attention from different sponsors. Pridopidine has shown a potential benefit for motor disability in HD3. The drug has a very benign safety profile, so we are currently planning to start a new trial involving 50 centers and around 400 participants in North America, Europe and Australia, which will increase the dose of the drug compared to previous trials. Unfortunately, this is necessary because the first two trials were formally negative, as the primary endpoint did not reach its predefined significance level. But, it is nice to see this drug get another chance, because currently, we only have drugs available for lowering the amount of involuntary movements. Pridopidine would fill a gap that we have not been able to address in a positive way. We have other compounds for which we expect clinical trial results sometime soon. There’s the exploration of slow-release forms of tetrabenazine, which may create additional benefit to patients and lower potential side effects. And there are a number of other compounds currently being considered for symptom relief, such as PDE10A inhibitors (see HD Insights, Vol. 5). Then there is the buproprion trial in Europe, which is trying to address the problem of apathy in HD. And of course we are expecting the results of the large HSG trials with CoQ10, which will be interesting to hear. We have other sponsors looking into microglial activation patterns that could potentially be ameliorated, and we could also potentially have treatment trials with sRNA addressing the lowering of mutant huntingtin in HD patients. This was the target of a trial with Selisistat for which I was the PI with Siena Biotech, the results of which will soon be available. We will have to see which of these approaches will contribute to our long-term aim to actually change the disease progression of HD.

HD INSIGHTS: Dr. Reilmann, thank you for your time, and for your continuing dedication to HD care and research.


A logo worth a thousand words:

logoOur logo has an interesting story, which encapsulates the excitement about the Institute among the HD community here in Münster. One of the participants in my research is a graphic designer with premanifest HD. When I told him about the Institute, he was so excited that he asked to design a logo for us. I wanted something very traditional, like a seal that we could put on documents, but he had another vision. The logo he designed symbolizes the autosomal dominant inheritance pattern between two generations. Imagine that above the second ‘G’ of ‘George’ is an individual with the HD gene and a recessive normal gene, and on the other side, another individual with two normal genes. The lines symbolize four offspring, two of whom have inherited the disease. When I received the email from him, describing the philosophy behind this logo, I was quite moved. And I think it tells us a lot about what patients are thinking: they are thinking about how this disease affects the next generation.


 

1 Tabrizi SJ, Reilmann R, Roos RA, et al. Potential endpoints for clinical trials in premanifest and early Huntington’s disease in the TRACK-HD study: analysis of 24 month observational data. Lancet Neurol. 2012 Jan; 11(1):42-53.

2 Biglan KM, Zhang Y, Long JD, et al. Refining the diagnosis of Huntington disease: the PREDICT-HD study. Front Aging Neurosci. 2013 Apr 2;5:12.

3 Reilmann R. The pridopidine paradox in Huntington’s disease. Mov Disord. 2013 Sep; 28(10):1321-4. doi: 10.1002/mds. 25559. Epub 2013 Jul 11. PubMed PMID: 23847099.