What does it mean to find a “cure” for a disease?

MRI Scan of one of my brain tumors in 2015

Unraveling the impact of the word "cure" on rare disease research

Every three months, I drive eight hours to a specialized clinic to find out if my brain tumor has grown – a trip I’ve been making for about 5 years. This isn’t my first tumor; I’ve had another one in my brain (which was removed in 2015 causing me to lose hearing in my left ear) and one in my spinal cord.

After each MRI appointment, I would typically learn that my tumor grew again, with the potential to significantly adversely impact my health – for instance, causing my balance to be shaky, losing my hearing completely or inducing facial paralysis. You can’t take these tumors out without compromising the nerves they grow on, so the only hope is to keep their growth under control.

At the start of 2020, I tried a new experimental drug currently on the market as an immunosuppressant , and, to my surprise, 3 months later the tumor was stable. I then realized that in many ways, as long as this drug keeps suppressing the tumor growth, I won’t have to worry about my rare disease anymore. I asked myself, in this instance, am I “cured”?

There are caveats, of course. I was diagnosed with this rare disease (it’s called NF2 and affects 1 in 40,000 people) at the age of 33, and it is now a part of my daily life. Even with this new relatively non-toxic drug, there are still side effects to manage. More importantly, there’s uncertainty about long term resistance to the drug and a big question remains: how long will it keep working? Nonetheless, at least for now, this drug offers the opportunity for the disease to have a relatively small impact on my day-to-day life.

In many ways, living with NF2 and finding my own approach to a “cure” has broadened my perspective. For example, despite losing my hearing in my left ear, I now listen with more appreciation with the hearing I still have. More importantly, if all the community’s research efforts would have gone towards “fixing” the underlying mutation that causes the disease, this repurposed drug that is currently working for me may have never been on my radar. It begs the question, what does it mean to cure a disease?

At Rarebase, we have learned that there is no single way to answer this question. The meaning and concept of a cure is deeply personal for each patient and their family. Does being cured mean that there is complete absence of a disease anywhere in the world? Are you cured when you correct the underlying genetic mutation? Alternatively, do you need to completely revert all symptoms from the disease to be cured? What if a cure for a patient just means getting a solid night of sleep? What if the cure changes who you are as a person?

We sat down with Tracy Dixon Salazar, Oli Rayner, and Wendy Chung to get their perspectives.

I saw the power of the word cure early on
–Dr. Tracy Dixon-Salazar

Dr. Tracy Dixon-Salazar is a neuroscientist, geneticist, mother to Savannah, and currently serves as the Executive Director of the LGS Foundation

In the beginning it felt so important to embrace the word cure because I didn’t want to set the bar at mediocrity, or even below mediocrity – such as just minimizing my daughter’s seizures and their side effects. Who’s going to get behind that?

Tracy Dixon-Salazar and her daughter Savannah. Photo by Joanna Rudnick/CZI.

CURE Epilepsy (a research foundation) started more than 20 years ago. They really embraced the word cure. The way that this decision pivoted the field was incredible. Their ideas began to bubble up from the surface and come out of the shadows. Scientists were now being asked to be innovative and creative to think about what they needed to do to cure epilepsy – not just to treat it. I saw the power of the word cure really early on.

But even still, it was really hard for me, training as a neuroscientist, to embrace that word for my own child. I didn’t really know how I defined a cure. At the beginning, I struggled with this for 7 or 8 years, before I finally decided that a cure to me would mean the complete absence of a disease.

A cure for Lennox-Gastaut syndrome (LGS) would mean there is no more LGS on this planet. And I have really mixed feelings about that because I actually don’t want to live in a world where my daughter does not exist; yet that’s what I am fighting for.

On the flip side, I also don’t want to live in a world where I see my kid have more than 40,000 seizures. That suffering that she lives through is so horrific.

What is my perception of a cure? More than twenty years into my journey, it is aiming for a complete absence of suffering.

Now I just feel very lucky, essentially cured, or “free” is probably a better word
–Oli Rayner

Oli Rayner has lived with and overcome Cystic Fibrosis. He has worked for the Cystic Fibrosis Foundation identifying and initiating new therapeutic development partnerships with biopharma, academics and accelerators in the UK and Europe.

When I was 3 years old, I was told I wouldn’t make it to 10. When I was 14, they said I wouldn’t make it to 21. This has been the story of my life.

I got really sick around 2010 -- to the point where I needed a lung transplant because I probably had 2 more years to live. Without a transplant I would have had complete respiratory failure. I managed to get a lung transplant in July 2017. Within 3 days of the transplant I was on an exercise bike.

I now feel as if I’ve been cured because it’s like I don’t have the disease anymore. I don’t have the symptoms and I don’t have to go in for the treatments. I say I have the disease because I know that’s technically right, but I want to say that I had the disease. Now I just feel very lucky, essentially cured or “free” is probably a better word; I’m liberated.

Cystic fibrosis is genetic, so my parents felt guilty that they had given it to me. We have had endless conversations about this. But I would tell them, there’s no version of me without CF. It’s who I am and it’s part of my genes. In many ways I was very lucky in the genetic lottery. I really like who I am and I really love being alive. And without them I wouldn’t have any of that, so it doesn’t make sense for them to say they feel guilty.

When you are born with a rare disease, you don’t know any different. Sometimes people say, “How do you cope with it?” or “It must be awful, how do you deal with it?” and that doesn’t really make sense to me. It’s a bit like saying what’s it like breathing oxygen? There is no way to answer it because it’s just who you are.

Cure with a capital C is a very tall order
–Dr. Wendy Chung

Dr. Wendy Chung is an ABMG board certified clinical and molecular geneticist with 20 years of experience in clinical research, largely for rare diseases. She leads the Precision Medicine Resource of the Irving Institute at Columbia University and is the principal investigator of the large U.S. study of autism, SPARK.

We always say the capital C-word, Cure, is the ultimate thing we’re striving for. We’re careful in terms of saying: disease modifying, disease altering, changing the trajectory, changing the burden – but Cure with a capital C is a very tall order.

Geneticist Wendy Chung helps her patient Susannah put on a doctor’s lab coat. Susannah suffers from a rare genetic disease, as detailed in a new documentary about the history of genetics. © THE GENE: AN INTIMATE HISTORY

With neurological conditions, I think a lot about reversibility. Can you really cure something, and how early do you have to get in to cure it? In some cases you have to get in prenatally to do so. I think it’s more about decreasing the burden of disease.

We start out very early in the process with “clinical trial readiness” -- having the voice of the patient, talking to the families, understanding what the pain points are for them in terms of disease burden, and understanding what would make a meaningful difference. For many families, getting a good night's sleep would make all the difference in the world.

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The strict definition of the word "cure" is complete absence and reversal of a disease, but in reality, the meaning of it is much more personal and nuanced. On one hand, aiming high can make us creative and excited (and we need that), but on the other hand, we may be more successful if we aim to find solid treatments that help us deal with the disease burden and improve our current quality of life.

What we’re fighting for as patients and patient advocates isn’t easy to achieve, so how we define our goals significantly affects our path forward. I believe it is ultimately up to the patients to decide what is important for them and how they would like to weigh the risks and benefits of any technology or therapeutic strategy. At Rarebase, our starting point is always the patient and we’re working incredibly hard to apply the latest technologies to the long tail of rare disorders, and bringing technology, science and patients together takes a village.

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