February 29 marks the ninth annual Rare Disease Day, a worldwide event devoted to raising awareness of more than 6,500 rare diseases, of which less than 5 percent have any available treatment. We spoke with Dr. Steven Walkley, director of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center and professor in the Dominick P. Purpura Department of Neuroscience at Albert Einstein College of Medicine, about his rare disease research and why he encourages his graduate students and postdocs to meet children and families affected by rare conditions. This interview was conducted by Sunita Reed, multimedia producer at Einstein.
Einstein produced a video in 2014 about your research on a drug, cyclodextrin, to treat the rare disease Niemann-Pick type C, featuring the Marella family, whose young son Andrew was in a clinical trial at the National Institutes of Health. Can you give us an update on the results of the clinical trial?
In fact, the news is very positive. Actually, a summary of the phase I trial will be presented by the lead physician, Forbes Porter, at an upcoming meeting of the Lysosomal Disease Network. There is every indication that the cyclodextrin treatment is significantly slowing the disease in children who are under treatment. The NIH of course supported all of that phase I study and it has now partnered with a commercial group, a company called Vtesse, that has taken over the phase II-III trial. The company is presently enrolling patients via multi-site recruitment worldwide for that phase II-III trial.
Have there been any challenges with the clinical trial?
The phase I trial has been carried out at the Medical Center at NIH and I'm not directly involved in that. But a group of us who have been linked to the phase I study, including NIH personnel, has bimonthly teleconferences to focus on what's happening with the trial. As with any new drug, there are some issues that have come up, one of which is pretty widely known: ototoxicity, meaning the drug causes some problems with hearing. So far I think in the phase I trial it's not been a major problem. But it's an issue that has to be carefully followed as we go into phase II-III, as the dosage of the drug will be increased.
Where does the drug stand within the FDA approval process?
Just a few weeks ago the drug received breakthrough status from the FDA, which means that the FDA will provide senior administrative leadership to help the company navigate the drug through this critical phase II-III period. It's a very positive development and is based largely on the success of phase I as well as on the very solid preclinical data that came out of my lab and other labs at the University of Pennsylvania and UT-Southwestern.
How would you answer critics who wonder whether funding should go to the study of rare diseases, since by definition these are conditions that affect a relatively low number of people?
Early in my career when I was working on rare diseases and they weren't as widely appreciated, study sections often responded by saying exactly that: "Why are you working on such a rare disease? Why don't you work on Alzheimer's?" But to me rare diseases are experiments in nature. They are disruptions in metabolic pathways, genetic for the most part, and by studying the outcome of that disruption, that is, by studying the disease, we can learn more about how the normal brain or other organs function. In doing so we may also gain insights into more prevalent diseases, for example Alzheimer's which has certain features in common with Niemann-Pick type C. On the human side, too, we need to understand rare diseases so we can better develop therapies for them.
What do you think is the most impressive advance or trend in rare disease research in, let's say, the last five years or so?
Well, certainly in the last five years there has been a consolidation around the recognition of the importance of rare disease. The U.S. now celebrates Rare Disease Day just as Europe and the rest of the world do. So there's that sort of broader appreciation; there's also the leadership of Dr. Chris Austin, the director at NCATS -- the NIH institute that's heavily focused on rare disease -- and on therapy through its Therapeutics for Rare and Neglected Diseases (TRND) program.
Many basic researchers who work on diseases or conditions spend their entire careers without meeting anyone who suffers from them. You've got a different view. And, in fact, you encourage your graduate students and postdocs to get involved with the children and families who are affected by these diseases. Why is that?
When I was much younger there was an organization called Science for the People, and I don't know what happened to that group, but the idea of it never really left my head. I mean, this is what science is for, right? It's to help us understand the world and help us understand disease as well, and by doing that help people who have these diseases. So I started out early in my career very much focused on questions that I had about the diseases I was working on, but it was only after I'd been doing this for a number of years that I happened to finally meet some families. This showed me the reality ... that the models we were working on were models of real diseases that real people had, and families were affected and individuals were affected. And it enriched my experience by getting to know these families. You learn very quickly about human nature and the meaning of love in a family by understanding what they go through. It's not that I think as scientists we need more motivation, but it's valuable to have this experience with the families.
How do you encourage your students to get involved?
I'm on the scientific advisory boards for a number of the family organizations for different lysosomal diseases, and I go to these meetings periodically. When possible I invite my students and postdocs to go with me. We also participate in fundraising activities for many of the groups -- bike-a-thons, walk-a-thons. And my students have become engaged beyond my wildest expectation. So we're really quite involved with the families. A number of the parents and the kids are friends of mine. It's just the way it's become.
This post was originally featured on The Doctor's Tablet, the blog of Albert Einstein College of Medicine.