COMMUNITY COLLABORATION TO TACKLE RARE DISEASES
Rarecamp uses open-source approach to empower individuals to create treatments
COVID-19 has been a great educator. Members of the public now toss around terms like viral load, safety, efficacy and herd immunity, often using them quite correctly.
The disease has also been an amazing unifier. One of the most common slogans, painted on walls, displayed in store windows, and even featured on a United Nations webpage is “We're all in this together.”
Numerous commentators have pointed out that actually “we're not all in this together” because COVID-19 has highlighted and even increased inequalities. If you're rich enough to get food delivered, and have a backyard, you're better off than many people. If you can work from home, you're one of the lucky ones. If you have access to a vaccine, which experts urge us to get as soon as possible, be thankful.
At the other extreme from virtually ubiquitous COVID-19, there are some very rare diseases. How rare? Although first reported in 1984, there has only been a single case of a boy with ribose 5-phosphate isomerase deficiency, an inborn error of metabolism which damages the white matter of the brain. In fact, Orpha.net, which tracks rare diseases, shows over 200 conditions that have shown up in just one person, or one family, since they are often genetic.
According to the Canadian Organization for Rare Disorders, “about 1 in 12 Canadians, two-thirds of them children, are affected by a rare disorder.” They also note that only 60 per cent of treatments for rare disorders make it into Canada and “most get approved up to six years later than in the U.S. and Europe.” This group defines a rare condition as one “affecting fewer than one person in 2,000 in their lifetime.”
Perhaps the best known rare disease affecting males is Klinefelter syndrome, also known as 47,XYY because of the presence of an extra Y chromosome. It doesn't technically meet the rare disease threshold because it affects about one in 650 newborn boys. Men with this condition used to be called “supermales” because of that extra male chromosome.
The U.s.-based National Organization for Rare Disorders (NORD) notes that affected individuals are usually very tall, with an average height of 190 cm. They typically have small testicles, severe acne in adolescence, and delayed puberty. NORD notes that while their intelligence is in the normal range, “learning disabilities have been reported in up to 50 per cent of cases.” Sometimes, males with this condition have an explosive temper and problems with impulse control.
One of the more bizarre male-only rare diseases is androgen insensitivity syndrome (AIS), which can result in a person who looks like a woman but is genetically male. In a 2003 review paper in the journal Gynecological Endocrinology, researchers from the University of Granada in Spain estimated it occurs once in every 90,000 to 100,000 live births. Because of a genetic abnormality, testosterone and dihydrotestosterone don't have their usual effect on the developing fetus.
So, while having the XY male genetic karyotype, an AIS baby may be born with female or ambiguous genitalia. Depending on the severity, sex assignment surgery may be necessary either in infancy or later in life. XY males with this condition are usually infertile, and XX females may be carriers. They don't display the symptoms because they have another X chromosome without the abnormality.
A recent announcement from the tech world may bring major changes to the treatment of rare diseases. The plan is to apply the same idea as hackathons, where people try to solve problems collaboratively. Sanath Kumar Ramesh, founder of the Opentreatments Foundation, announced that “If it's not yet commercially viable to create treatments for rare diseases, we will take this work into our own hands; with open source software and community collaboration is the way we can do it.”
Ramesh's passion for this project is driven in part by love for his two-year-old son Raghav. The boy is one of just nine children worldwide identified as suffering from Sedaghatian type Sp on dy lo meta phys eal dysplasia. The condition makes him unable to sit, stand, walk, or eat and drink normally.
The new project, called Rarecamp, will use an opensource approach to “decentralize drug development and empower patients, families and other motivated individuals to create treatments for diseases they care about.” They have prominent medical partners like the Baylor College of Medicine and Odylia Therapeutics and the support of groups like the Linux Foundation.
Ramesh notes that many rare diseases already have passionate volunteer organizations.
The new platform will enable “patient-led organizations to develop treatments using the Adeno-associated virus gene therapy technology. It provides a robust roadmap, advice from drug development experts, and research infrastructure (labs, contract research facilities, manufacturing facilities, software tools) to execute every step of the drug development pipeline from planning, design, manufacturing, all the way to clinical trials.” Ramesh says they will then
“hand off these therapies to commercial, governmental and philanthropic entities to ensure patients get access to the therapies for the years to come.”
It's an ambitious and audacious undertaking, but the opensource approach, where smart people around the world put their heads together, has worked many times before. Let's hope they have great success with this one.