Genetic testing for rare conditions and educating the next generation of clinicians on CTX
Yaz Kisanuki, MD, of the Department of Neurology at The Ohio State University Wexner Medical Center, talks about educating the next generation of clinicians on rare genetic conditions like cerebrotendinous xanthomatosis and the importance of early diagnosis and treatment to avoid more progressive neurodegeneration.
Question:
You are involved in research surrounding spinocerebellar ataxia. Can you talk about any of those studies or generally discuss the landscape of treatment and research for this group of conditions?
Yaz Kisanuki, MD:
I think that they know that in terms of the genetics of the spinocerebellar ataxias, this is a still evolving area and we discover new genes one after another even within the last couple of years. I think before we know more detail of the genetics, a patient with the CA is critically very similar in terms of how they present and some of them are autosomal dominant and the autosomal recessive, X-link, you name it. But the previous attempt was like, “Can we treat more like an entire group of these patients?” The answer is not so, I’m going to say, productive in that type of approach, with some exceptions that they know.
For example, like Friedreich ataxia, there’s already FDA-approved medication to try to slow down the progression, SKYCLARYS, that has been approved for in a clinical practice. There’s one approach for the disease modifying therapy, and I think there might be one medication coming up on the horizon because we heard about some promising result using the bioequivalent medication for riluzole. Riluzole is approved for the ALS patients for the disease-modifying purpose. They did the trial [on] riluzole, which is done by the pharmaceutical company and I think they recently announced some promising result, but it’s not yet approved by the FDA yet.
Now probably the more important landscape in terms of these genetic disorders are, we are entering the gene therapy era and this is already happening in the other genetic neurological disorders. I think that we do have the tools to apply for the human patients. I think we still need to work on the details, how to safely deliver those product and also to make sure that it is efficacious. But we are entering the new stage to try to directly aim for the cause of these disorders because previously a number of the genetic disorders are able to be diagnosed, but we always been told that, “What are you going to do about this? Is there any treatment available?” Now we can change some tone of the discussion to say, yes, that we do have some potentially available treatment in the near future. I’m very actually excited about this time point because we are entering a new phase of very difficult genetic disorders.
Question:
You are the director of the Department of Neurology residency program. How do you educate the next generation of clinicians on rare conditions such as cerebral tendinous xanthomatosis and how to help patients with rare conditions?
Yaz Kisanuki, MD:
Obviously that delivering this important layer but still basically the disease you don’t want to miss type of disorder, is very important for the next generation of providers. We do provide lectures like trying to go over some of the highlights of genetic disorders, including CTX and the other spinocerebellar ataxias. Even though we need to still teach about the standard of care, meaning that FDA-approved current treatment, but we also emphasize that some of the emerging research areas to the learners to say even though you might not entering this kind of rare disease field, but this is something you may encounter as neurology practitioners, no matter which area you might go, and I think this is still a treatable, preventable disorder. The earlier diagnosis is very important, particularly the CTX. I think that I’ve been trying to emphasizing at least during the lecture once a year to trying to put this into the couple slides.
Actually, I do see some very small world, but some outcomes. Some of the graduates of who I trained, I mean before I become a program director, and they actually start with a collaboration with the local provider and then they do diagnose CTX and then they finally contacted me to say, “Dr. Kisanuki, we have a potential patient within Ohio. Can you please see this patient just to confirm that what we are doing is reasonable in management and stuff?” It’s a small scale, but we do see some outcome that they do recognize this disease, even they are graduates and they do communicate. I think that the education is very important to teach about rare but still important disease like CTX.
Because I have to go back to my first patient experience. Some patients come in siblings because this is autosomal recessive disorders. I had one patient who primarily developed as a progressive ataxia with the cognitive decline in his forties. As soon as I diagnose this patient, I asked to reach out to his siblings and actually his younger brother also got diagnosed as well. But the big difference between these brothers, the older brother who already becomes symptomatic, despite that we aggressively treat him with the chenodeoxycholic acid, unfortunately, after about 6, 7 years later, he unfortunately further progressed his, both cognitive decline and ataxia symptom. Again, due to the aspirations he [is] deceased unfortunately. But the younger brother, we caught him while his symptoms are almost zero, I mean like almost none, and only the very minor exam finding when I saw him at the first time. We’ve been treating him and he’s a very high functional person, no physical limitation. He’s been maintained very, very well.
That’s how important it is. If we diagnose the condition ideally before they become really symptomatic, we can treat him, treat those patient without going to the devastating neurodegenerative process. I just need to emphasize that this is very, very rare, but you don’t want to miss this disease because there’s a window of opportunity to change the outcome significantly. That’s just my delivering the take-home message for the potential audiences.
Question:
Is there anything you’d like to add about CTX for the audience?
Yaz Kisanuki, MD:
I think that in case for more like neurology practitioners, who do see patient in the community, if they see any patient which might have a question or a possibly belong to the CTX patient, like if your clinical suspicion lays and you experienced some difficulty how to confirm the diagnosis, while you’re not so sure about that, I think that referral to the tertiary care center is very important when it comes to that point. The sooner you refer to the tertiary care center like us, we can try to facilitate the workup. Then currently the medication is only available from the one pharmaceutical company and it takes us some effort to try to get the medication to be available for the patient. Tertiary care center providers are more familiar about those type of logistics. I think that that’s also another potentially the take home message for the audience, I think.
