Three years ago, at a New Jersey conference, three patient groups focused on the rare neurodevelopmental condition, alternating hemiplegia of childhood (AHC), put aside their differences, and decided they could accomplish more by collaborating rather than competing.
The impetus for the cooperation was a potential gene therapy strategy that one of the groups shared with the others. Now, the three AHC groups—Hope for Annabel, Cure AHC, and the AHC Foundation—are collaborating on one of the early data collection programs on the RARE-X platform.
Though it may seem odd to people outside the area of rare disease, patient groups seeking the same goals all too often look at each other as competitors rather than partners as they vie for funding, researchers, and patients.
“When we started Cure AHC, we were coming into a space where there was an organization that already existed in the United States. We felt we had additional value to bring. We had opportunities to drive things forward and do things that weren’t happening,” said Bill Krenn, vice president of Cure AHC. “What really brought us together in the past few years, which we didn’t have before, was a clear, unifying goal and a real potential for something great to happen, which was genetic therapies.”
AHC is an ultra-rare disease, affecting about one in a million people. There are approximately 300 patients with the disease in the United States and approximately 1,000 worldwide. Symptoms vary, but can include temporary paralysis, painful muscle contractions, episodes of reduced consciousness, seizures, difficulty with muscular coordination, gait abnormality, motor and speech delays, autonomic system malfunctions, and behavioral issues. Unfortunately, because of the rarity of the disease and the inconsistent nature of AHC symptoms, many children are not diagnosed or are misdiagnosed for years.
While there have been several separate efforts to conduct natural history and other studies of AHC, advocates say the pace of academic research has been slower than they would like and the studies are not robust or precise enough to satisfy the needs of regulators or drug developers. Moreover, they state having difficulty getting researchers to use common terminology across their datasets or share them with others to advance research.
“The hope was to accelerate the path towards therapies by gathering precise data—the exact data that end-users like pharma and FDA need – and layering and supplementing those data with the data that we are already collecting in the other natural history studies,” said Simon Frost, president of Hope for Annabel and a director of Cure AHC. “It seems like this is the best way to do that, especially with RARE-X’s federated database design.”
The AHC Data Collection Program is among the first RARE- X programs conducted in partnership with rare disease communities. RARE-X is applying technology powered by the Broad Institute of MIT and Harvard that has been proven in other large-scale public health and genomic data-sharing initiatives to support researchers developing treatments for rare disease patients. One major difference from this and other AHC data efforts is the AHC Data Collection Program is patient-owned.
“What makes it particularly different and valuable is that we own the data as parents. When we put the data in, we can get it back. We’ll be able to control it. We can say if we want it to be included in a research study. We can say, we don’t want it to be there,” said Joshua Marszalek, president of the AHC Foundation Board of Directors. “In all of the databases that have been produced, they’ve all been researcher databases. When we put our information in, it goes into a black hole, and we have no say as parents. What are you guys doing with that stuff?”
To participate in the effort, all patients need to do is log into the RARE-X platform and complete a series of surveys over time. The initial surveys involve general information about a patient, their general medical health, and quality of life. Then, as new survey modules are added to the system around specific systems and topics, participants will be invited to answer more targeted questions.
Megan O’Boyle, patient engagement lead for RARE-X, is working closely with organizations to help them engage their patients and guide them as they navigate the process. She said a challenge organizations have is getting some patients and caregivers to participate because they feel they lack the expertise to fill out the surveys, fear medical research, or think that treatments and cures are too far away to benefit them.
“There’s nothing that we’re asking at this level that you can’t answer on your own,” O’Boyle said she tells them. “All those days that you feel like there’s nothing that you can do to help your child—this is something you can do. You are providing data that will attract researchers, lead to more knowledge, and possibly drug development.”
Ultimately, what has the AHC community excited about the potential of RARE-X is not only the opportunity to collaborate with other patient families with the same condition, but also to leverage data from patients across multiple conditions that may shed light on its own.
“It seems that this is the way to scale beyond single diseases because when it comes to gathering data most disease communities do the same things. One of the things that we all do is to try to diagnose a genetic disease as quickly as possible. Another is to identify therapeutic targets by gathering usable genetic and clinical data. It seems that gathering large sets of genotype and phenotype data in a very coordinated way is scalable and correlatable across multiple diseases to diagnose better, to identify therapeutic targets better, to work with other disease communities better, especially to understand what they have done successfully, and to roll out a more standardized program for all rare diseases,” said Frost, who is also a director of the RARE-X board. “In my case, I’m very interested in other neurological disorders and how we can all benefit from each other’s work and coordinate to create best practices and protocols to identify therapeutic targets quickly and understand our diseases better, especially genetic and phenotypic correlations and causations.”