Let's Learn About Rare Disease Day

Feb. 28 is Rare Disease Day. But you might be surprised to learn many of these diseases really aren’t as “rare” as you might think.

A rare disease is defined as any disease affecting fewer than 200,000 people in the U.S.¹ While individually, each of these diseases is rare, as a group, they are quite common. As many as 1 in 10 individuals may have a rare disease and half of those are children.

Importantly, up to 80 percent of rare diseases have a genetic basis yet only 5 percent of these diseases have treatments.² For these reasons, it’s important to bring awareness to rare diseases and to continue developing expertise and support for research to find cures.

M. Scott Perry, M.D., medical director of Neurology and the Genetic Epilepsy Clinic at Cook Children’s, discusses some of the rare diseases he cares for and how bringing awareness to these conditions can impact patients with other conditions.

What are some of the rare diseases you encounter in your Genetic Epilepsy Clinic?

Two of the most common conditions I treat are Tuberous Sclerosis Complex (1 in 6,000) and Dravet Syndrome (1 in 20,000), though I encounter a variety of other rare genetic-based epilepsies on a daily basis. Tuberous sclerosis is estimated to affect approximately 50,000 people in the U.S and presents with a variety of tumors that can grow in the heart, brain, kidneys and eyes – as well as skin manifestations, seizures, and delays in development. Dravet syndrome may affect as many as 1 in 16,000 children in the U.S. and presents with seizures – often prolonged seizures with fever initially which evolve to multiple other seizure types including tonic - clonic, absence, myoclonic and “drop attacks” by age 2 years. Children are often normally developing initially but demonstrate a slowing or decline in development after onset of their seizures. For both of these conditions, the epilepsy is a major component and often seizures are resistant to the available treatments – thus one reason for continued research.

How have you seen research into these conditions change treatment?

So often with neurological conditions, especially epilepsy, we’ve focused on treating the symptoms – meaning the seizures. Both of these conditions have a genetic basis that results in seizures, but also a host of other problems such as difficulties walking, problems with sleep cycles, behavior, and feeding for example. By understanding the genetic basis of the disease, we hope to develop therapies targeted at the source of the condition, such that multiple symptoms can be treated and one day the disease cured. For tuberous sclerosis, understanding the genetic mechanism of the disease led to the development of everolimus, a drug that targets an important step in tumor development in this condition. By using this drug, we now have a way to stop or slow the growth of some of the tumors in this condition. The drug has also shown ability to reduce seizures in children with tuberous sclerosis.

For Dravet syndrome, several new drugs have been investigated and either approved (Epidiolex®/cannabidiol) or submitted for approval (Fintepla®/fenfluramine). These drugs, along with stiripentol (approved 2018), are the first drugs to be studied and approved specifically for Dravet syndrome. We know the gene which causes the majority of Dravet syndrome is SCN1A which encodes a sodium channel important to brain function. Researchers are now developing treatments which target genes which regulate how much SCN1A is made to increase the availability of healthy SCN1A in these patients. This treatment (antisense oligonucleotides) gets at the root cause of the condition and holds potential to treat seizures and many other complications of the disease – potentially reversing it completely one day.

Does Cook Children’s participate in research for rare conditions?

Absolutely. In Neurosciences we have recently participated in trials of both Epidiolex and Fintepla for Dravet syndrome and Lennox Gastaut syndrome. We are preparing to launch additional drug trials this year for these conditions as well. I have been working with researchers to develop trials for antisense oligonucleotides mentioned earlier. We are also planning to start a trial for CDKL5, another rare form of genetic epilepsy and we participate in collaborative studies of tuberous sclerosis.

Why is it important to study rare diseases?

As we said earlier, while these diseases are rare they are actually quite common as a group. As many of these diseases have a genetic basis, research into cures directed at this genetic etiology potentially hold clues to curing a number of conditions. If we can find a method to correct the gene dysfunction in Dravet syndrome, then we may be able to apply the same science to cure other genetic epilepsies such as SCN2A, SCN8A, KCNQ2-related epilepsy, etc.

What are you most excited for in the coming year for treatment of rare disease at Cook?

This summer we plan to open our Adult Genetic Epilepsy clinic. One of the great things about research into rare diseases is that we are now seeing kids with these rare syndromes live to be adults. The downside is that adult providers have never had experience with many of these conditions and are mostly unprepared to care for them the way we do. In addition, we don’t know a lot about how these rare epilepsies act in adulthood – do they develop new or unique symptoms as adults that we didn’t see as children? The Adult Genetic Epilepsy clinic will be staffed by myself and an adult epileptologist who will work with me to care for these patients – ultimately developing the expertise needed to provide the best care as they transition to adulthood. We hope to use this clinic as a model for other institutions to implement similar clinics in the future.

1. FDA Office of Orphan Products Development.
2. “Rare Diseases and Orphan Products: Accelerating Research and Development” Committee on Accelerating Rare Diseases Research and Orphan Product Development Board on Health Sciences Policy.