Dr. Surendran Covers Patient Registries and Unmet Needs for Alagille Syndrome
Kameswaran Surendran, PhD, Associate Professor of Basic Biomedical Sciences at the University of South Dakota, discusses the importance of patient registries for Alagille syndrome and continued unmet needs for this patient cohort.
Hear Dr. Surendran talk about exciting research in Alagille syndrome.
Question:
Can you talk about the ALGSA/CoRDS Alagille Syndrome patient registry and the importance of such registries for this patient population?
Kameswaran Surendran, PhD:
Since Alagille syndrome is rare, having the patient registry such as CoRDS and advocacy groups such as the Alagille Syndrome Alliance is really critical, as it helps to connect the patients with a diverse set of researchers who are interested in that disease. I think it empowers both the researchers and the patients and it kind of provides an opportunity to better understand the nature of the disease, especially when it is highly variable. These registries can really help to determine what are the common disease characteristics or symptoms that people are experiencing and what are some of the rare symptoms people are experiencing. It can also help to further understand why there is variability, which is kind of what I’m trying to make use of it for. Eventually, I think it can also help when there is a therapy that comes about to do clinical trials, I think it would be helpful to have these registries so that the right people can be contacted to participate in these studies.
Question:
What are the continued unmet needs for patients with Alagille syndrome, and what are your recommendations for addressing those needs?
Kameswaran Surendran, PhD:
My understanding of this comes from, I am a researcher, but I’ve had the privilege of interacting with people who are living with Alagille syndrome and those caring for people with Alagille syndrome, and it’s through that interaction that I’ve become aware of some of these issues that they run into. One of them is actually a lot of the family members have kids who have been diagnosed with Alagille syndrome. However, they themselves don’t know whether they have the disease or not. Some of them suspect that they do, but for whatever reason, primarily financial, they’re not able to confirm whether they also have the disease, and it would be, I think as a society, important that our healthcare system allows for the parents to also get genetically tested, especially when their kids have a disease such as Alagille syndrome, which has a genetic component.
I’ve also come across the opposite situation where whole-exome sequencing or genetic testing has been done and a person doesn’t have the typical characteristics of Alagille syndrome, and so the medical doctor has done genetic testing. They’ve even identified a mutation in NOTCH2. However, the particular change in NOTCH2 isn’t something that has been … it’s not clear whether that’s problematic or not. It’s a variation of unknown significance, and so there’s a hesitancy to actually say that that person has Alagille syndrome, and I think the medical doctor is doing the right thing there because they don’t have the typical symptoms and the mutation that identified is, it’s unclear whether it’s actually problematic or not. In this instance, I think it actually falls on researchers like myself to actually study the different possible mutations that can happen in a gene like NOTCH2 ahead of time, so that we kind of have a database of, these are likely going to be problematic as opposed to these other ones are not.
It’s a tall order, but it’s something that where we I think hopefully can get to where ahead of time we know which of the mutations are likely to be problematic versus not. That can really help with diagnosing Alagille syndrome. Another aspect that I think is sort of an unmet need is it’s not really clear what an adult patient with Alagille syndrome is going to encounter. This is partly because adults weren’t really being diagnosed with Alagille syndrome without the genetic testing. One of the things that I think that’s sort of missing currently is that, as I mentioned, there’s a huge body of knowledge about notch signaling. A lot of studies done in different animal models where Notch signaling has been mutated only in the adult setting. It sort of helps that there is a knowledge base that can sort of predict what might happen in adults that don’t have a normal level of notch signaling, and I think we can tap into that as a way of foreshadowing what an adult person with Alagille syndrome might encounter.
Of course, the final thing that we all hope for is some way of slowing down the disease, whether it be in the kidney or the liver. That’s definitely an unmet need, and I think that’s where basic research comes in and hopefully we can change what is available in that aspect.
Rare Disease 360® is the Official Media Partner and Official Publication of The Alagille Syndrome Alliance (Alagille.org).
