This is a part of an awareness-driving initiative to help families who may be living with Farber disease. If you believe you or your loved one have the symptoms of Farber or have been diagnosed with Farber, please get in contact with our team at patientinfo@aceragen.com.

M&B Sciences Team: Can you tell us a little bit about you and your background and your training?

Dr. Solyom: Sure. I’m a pediatrician by training with a special focus on pediatric rheumatology and rare diseases involving inflammation and inflammation of the bones and the joints in particular.

alex-solyom-md

We work with a lot of patients who are dealing with inflammation, especially arthritis patients. I know you've done a lot of work specifically in Farber disease. And we're going chat a little bit about that. Can you tell us what exactly Farber disease is?

Sure. Farber disease is a genetic disease. It’s caused by, the symptoms are caused by the abnormal buildup of a material called ceramide, which is a part of the normal structure of cells and tissues in the body. But this material builds up, because there’s an enzyme deficiency.
The deficient enzyme is called acid ceramidase and the gene that codes for it is the ASAH1 gene. That is its abbreviated name. That deficiency, the enzyme deficiency, leads to a buildup of this material. This material has an inflammatory role in normal function of cells when it builds up.

When there’s too much of it, then you get a lot of inflammation. And that inflammation in Farber disease is in the joints. It’s also in the tissues just below the surface of the skin.

That means that you have arthritis in the joints and you have some nodules or bumps, sort of inflamed bumps on the skin. And then it also affects the tissue in the larynx, which is the area around the vocal cords. And you can also have a hoarse voice. And there’s some other tissues that can be affected. It can affect the brain and the lungs as well. But those first three symptoms I mentioned, the joints, the nodules and the hoarse voice, those are the real typical symptoms of Farber.

And it's generally diagnosed at a fairly young age, right?

That’s right. Like a lot of other genetic diseases, the first symptoms usually appear in early childhood. You might say preschool age or even younger. But they don’t always have to appear together.

It can take up to three years for each of these symptoms or all of these symptoms to appear together. This is one of the things that makes it difficult to diagnose.

It can take up to three years for each or all of [the three cardinal symptoms] to appear together.

Have you treated Farber disease patients before?

I’ve been part of their care. I haven’t treated any Farber disease patients as a physician in charge of their care. But as a consultant in these types of diseases among a network of other physicians, I certainly have been a part of the treatment of children and adults with similar diseases.

It’s interesting, because it’s ultra rare. There’s only been a pretty small cohort of actual diagnoses. Is that correct?

It is considered ultra rare and I think the thing that we’re describing, we’re discovering in some of these diseases, is there’s really a spectrum of phenotypes, which means the physical presentation of the disease that’s much, much broader than originally thought. I think there are many more patients out there then we know of right now or have historically recorded in the literature. But certainly it’s a very, very rare disease.

We’re finding that there are diseases that can present very similarly to JIA like Farber with this typical arthritis that can look exactly like a JIA patient’s arthritis.

We’re often seeing that Farber disease is misdiagnosed as JIA or Juvenile Idiopathic Arthritis. Why does that happen?

JIA is an abbreviation for Juvenile Idiopathic Arthritis and starts in early childhood in most cases. And there is a spectrum within JIA.

The fact that there’s a broad spectrum of kids with arthritis in several joints with pain and really the impairment of their everyday function because of this arthritis, even atypical cases tend to get grouped into this one sort of large cohort of JIA.

We’re finding that there are diseases that can present very similarly to JIA like Farber with this typical arthritis that can look exactly like a JIA patient’s arthritis. They can have synovitis, an inflammation of the surface of the joint.

They can have effusion – swelling in the joint. They can have real pain, real inflammation, including inflammation that’s registering in the labs that are usually done to monitor patients with JIA. It can be a really confusing picture. And certainly, it’s easy to make the mistake or say, let’s make the diagnosis of JIA in a Farber patient. Particularly early on.

Because this is presenting in children, it will need to be parents or the primary caregiver who’s involved in the care of their child to say that the diagnosis does not seem correct. How do you recommend that a parent talk to a physician about that?

First, I think there are a couple of things that are important to recognize in a Farber population that might help differentiate Farber from JIA.

For example, it’s very rare to have subcutaneous nodules or these little granulomas like skin colored pretty pronounced bumps that we see in Farber. It’s pretty rare to see that in JIA. The presence of those types of bumps, that’s really something that would warrant further exploration and particularly testing for Farber.

I think that in cases like that, then certainly a parent would want to just ask their doctor or ask their child’s doctor, if they feel that these symptoms can be explained as a typical symptom that’s associated with JIA or whether there’s a possibility that some further diagnostic work could be done.

Then they can bring up the fact that they’ve heard about this disease called Farber and either present some of the information that they’ve obtained to the physician or give the physician the web address or whatever materials that they have so the physician can explore themselves.

But I would say that in the cases where the symptoms are pretty difficult, then it’s important for the possibility of Farber disease to be considered.

On the horizon: Farber disease treatment

I’d love to shift gears a little bit and ask you about what’s coming down the pipeline because at Aceragen, you’re beginning to develop a potential treatment for patients with Farber disease. Could you tell us a little bit more about the science behind your up and coming first in human trial for Farber disease?

I’m happy to. Because this is a missing enzyme, the easiest way to treat the disease or the most straightforward way is to give … it’s not a missing enzyme, but the enzyme is dysfunctional. It’s not able to perform its normal function because of the mutations. The easiest approach is to try to replace that enzyme or at least provide functional enzyme, enzyme that works in the place of the enzyme which isn’t working. And this has been done for a number of other diseases successfully so far over the past 10, up to about 20 years now.

We’re really following on the science that has already been really well established. And the question is, of course, how to demonstrate that this may have an impact in Farber disease? This same approach? We’ve done studies with collaborators in academic research hospitals trying to better find the disease in humans and also to find animal models that can reflect the disease.

And we’ve been able to test the drug substance, the enzyme replacement therapy, it’s called, in those animal models and we’ve seen promising results.

This is how the strategy works. We find first the way of producing an enzyme that we could use to potentially give back to the patients which they’re missing. And then, we test again in animal models and hopefully move forward into the clinic.

That’s where we are right now and we’re getting ready to hopefully initiate clinical trials for patients with Farber disease.

That’s an exciting place to be.

Absolutely.

And correct me if I’m wrong, but you completed a natural history study too, which generally does help inform some of the work that you end up doing in the first in human study, from my understanding. Is that correct?

That’s right. Part of this whole process of developing a drug or a treatment or a therapy for rare diseases was to better understand the disease itself so that you know what you measure when you try to measure the efficacy of the drug, see how it works and make sure that it’s safe.

And I think that one of the best ways to collect all the information was through a natural history study, where we looked at the medical histories of patients and we also followed them over time to see how their particular symptoms changed and either become worse or stayed the same over a period of time that would be similar to the period of time where we’re anticipating treating them in the clinical studies with that potential enzyme replacement therapy.

Listening to patient stories

How important would you say patient engagement is and the patient perspective is in the work that you’re doing as Senior Vice President of Rare Disease Development at Aceragen?

Well, it’s really one of the most important ways that we can make sure that we’re addressing the questions that are most important to patients, also parents of course, from the point of view of safety, from the point of view of understanding what’s happening to them because of the symptoms of Farber disease.

And also what they might expect in the clinical trial for a potential treatment. It’s really a collaboration and I think that everybody on our team is very much oriented towards making sure that patients are an integral part of how we develop these types of therapies.

That’s a great answer. That's very important to us here at M&B Sciences; it's always exciting for us to hear fellow companies who are really dedicated to keeping the patient voice at the center of their work.

We applaud you for that. And so because you've been working with patients and caregivers and parents, what would you say, and it doesn't even just have to be at Aceragen, but over your career as a physician and as a medical director, what have you learned from patients?

Well, I think that it's just really important to first understand the stories, so the whole narrative of how people live with the symptoms related to a disease and what challenges they face, even outside of the medical challenges.

What does it mean for them in a community, going to school, going shopping, looking for shoes, all those little things that seem very simple or very small parts of every day living for a lot of people, but I think it's never to be taken for granted in anybody, in the case of any patient or their parents who are dealing with a chronic disease and something that I really learned to look for.

To make sure to consider all of the practical questions that are really most important to be addressed. Because sometimes it's really impactful to make even a small change in a patient's life or a family's life. And we want to make sure that we don't underestimate how important that is and we make sure that we are aware of the expectations of patients and parents.

Child with Farber's playing with toys

Patients Have Power

Just one final question for you. What does “Patients Have Power” mean to you?

Well, this may seem like a sort of a formal answer, but it means that patients are stakeholders. So a stakeholder means they're a part of a process and part of, in this case, say the development of medicines or therapies, meaning that they have a role in impacting in how this development is done by actively working to make sure that companies and doctors are aware of what's concerning them.

Patients are stakeholders.

Also, so that they are advocates on their own behalf and as a group for either appropriate health care or reimbursement or their access to medications. And then also so that they have the power to support each other, I think, which I something that's very important. Even when, particularly in rare diseases, many families and patients are isolated in their own communities or don't have other patients around them who have the same condition or are dealing with the same issues.

And so the power is also there to have an impact even within the community, not necessarily only looking to work through physicians or health care systems, but also just with one another. And I think that's pretty powerful as well.

Patients have power

A big thank you to Dr. Alex Solyom for chatting with us as part of our collaboration with Aceragen!

This is a sponsored post.