If you scroll through databases of children and families who are part of the rare disease community, vague words like “unknown” and “undiagnosed” appear over and over again.
Alexander: Mitochondrial disease
Bertrand: Unknown lysosomal disease
Connor: Rare chromosomal disorder
Eithene: Unknown genetic disorder
Some disorders are too rare for most physicians to have heard of them; others are completely new mutations.
Ambreen Sayed, a PhD student at the University of Maine’s Graduate School of Biomedical Science and Engineering who researches rare neuromuscular diseases, recalls her time interning in a hospital’s genetics department: “Nobody knew the name or proper treatment for a disorder affecting a particular child that was brought in, so the child couldn’t be effectively diagnosed or treated. I had always thought science treats everyone equally,” she says.
“That was one of the first instances where I was exposed to the fact that not every problem has a proper scientific name or definition, let alone people who want to work on the issue. That’s when I decided I wanted to work in the field of rare diseases,” says Sayed.
Although each rare disease affects fewer than one in 1,000 individuals, they collectively affect one in every 10 Americans, according to the National Institutes of Health. A select few — such as cystic fibrosis, ALS, and Huntington’s disease — have gained attention and research funding through mass awareness efforts and celebrity involvement, but most of the 7,000 known rare diseases remain completely unfamiliar to the general population and much of the medical community.
Lack of awareness about rare diseases both hinders diagnosis and hurts patients’ ability to access adequate treatment.
“Since there are so few cases and a limited number of doctors who have heard of it, children suffering from ROHHAD [rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation] often have to travel to other parts of the country for proper medical attention,” explains a parent advocate on the ROHHAD Fight Inc. website. In addition to raising awareness and funding research, rare disease foundations like ROHHAD Fight try to help ease the enormous financial burden that comes with rare diseases, most of which are genetic and therefore persist throughout patients’ entire lives.
With the help of foundations, blogs, and social media, rare disease patients and their families have reached out and turned to one another for support and insights. And they don’t form connections solely with those who share their specific diagnosis. Struggles and coping strategies are common across many rare diseases. As a result, the entire rare disease community is well-connected and active.
Luke Rosen, an actor who founded KIF1A.org after his daughter’s diagnosis, is a dynamic part of that community. KIF1A-related disorder is a rare neurodegenerative disease that wasn’t identified until 2011, so Rosen and other KIF1A advocate families were starting from the ground up. “I feel like KIF1A has been welcomed so generously by the rare disease community as a whole,” reflects Rosen. “People from many groups have gone out of their way to help us raise awareness and guide us in terms of advocacy and patient support.”
The rare disease community has one thing tying them together above all else: They’re desperate for cures and preventions, not just ways to manage symptoms. But pharmaceutical and biotech companies have little financial incentive to develop drugs and technologies for these “orphan diseases,” so called because treatments are usually not expected to generate enough revenue to cover development and marketing costs.
Rosen says, “The rare disease ecosystem is almost entirely a ‘pay to play’ culture. The foundations who are able to fund a fleet of scientists to work around the clock, hire researchers, and rapidly generate huge fundraisers are the foundations who can truly drive a drug or gene therapy to market.”
Unfortunately, those foundations are few and far between.
In the 1980s, lobbying from the National Organization for Rare Disorders helped the U.S. government realize that the existing drug development system would likely doom most rare diseases to remain untreated orphans forever. To fight against that eventuality, Congress passed the 1983 Orphan Drug Act (ODA), which uses tax credits, grants, and extended market exclusivity to incentivize development of rare disease treatments.
Other countries, including Japan and members of the European Union, followed suit in subsequent years. In 2002, the Rare Diseases Act strengthened the work of the ODA by establishing the Office of Rare Diseases and increasing research funding.
Proponents of the ODA say it is one most successful pieces of U.S. health legislation ever enacted. The Food and Drug Administration website states that the Office of Orphan Products Development “has successfully enabled the development and marketing of over 600 drugs and biologic products for rare diseases since 1983. In contrast, fewer than 10 such products supported by industry came to market between 1973 and 1983.”
Disappointingly, this progress has barely made a dent in the problem. Even with government incentivization, it’s still hard to get a sufficient number of researchers and companies interested in rare diseases. As of 2011, the Orphanet Journal of Rare Diseases reported that 95 percent of rare diseases still lacked treatments.
“There are so few affected families and children that not very many big pharma companies divert resources toward rare diseases,” says Sayed. “I think they figure, ‘Why treat one in a million people when we can treat so many others?’”
That question looms large in the world of rare disease research. Why spend resources on rare diseases, however terrible they may be, when other diseases kill millions each year?
The answer is multifold. Perhaps most obvious is the moral argument against abandoning patients simply because there aren’t enough other people who will benefit from the research.
Rob Burgess, a researcher tackling exceedingly rare forms of Charcot-Marie-Tooth disease at the Jackson Laboratory, argues that it doesn’t make sense to focus only on the most prevalent diseases. “If we all did that,” he says, “the entire biomedical research endeavor would be devoted to heart disease, cancer, and maybe something like Alzheimer’s. That’s underserving everybody else.”
For skeptics who remain unconvinced, a more pragmatic argument exists: In today’s golden age of genomics and precision medicine, it is becoming increasingly likely that researching one disease — rare or otherwise — will uncover insights that will prove useful in treating a multitude of other diseases.
Dr. Wendy Chung, who directs the clinical genetics program at Columbia University, said in an interview on KIF1A.org, “By coming up with the treatment for KIF1A, it’s very likely that whatever we learn about that process is actually going to be applicable to other related conditions.” In this way, research that is originally focused on a small group of patients could ultimately affect a much larger population.
Other researchers echo Chung’s reasoning. “If we learn something that’s part of a pathway, our model might be applicable to a lot of other diseases that share the same pathway,” says Greg Cox, a colleague of Burgess’ who studies multiple rare diseases, such as spinal muscular atrophy.
While patients, families, and researchers all feel a constant sense of urgency, they also realize that the process from research to clinical impact is often a crushingly long haul. “I don’t discover something new every day, or even every year,” says Sayed.
Instead, Sayed focuses on the bigger picture. The muscular dystrophy she studies affects very few people, but when it does, it appears at birth, affecting babies in such a manner that they cannot walk or talk and have severe cognitive disability. Sayed says, “Knowing that I’m going to eventually find something that helps them live a higher-quality life is what keeps me going every day.”