Rare Diseases: Small Numbers, Big Problem - Part 1

They Escape Notice, but ‘Rare’ Diseases Are Anything But. Nearly 8% of the world’s population — 350 million people — have a rare disease. And diagnosis and treatment are advancing.
by Chris Adams, National Press Foundation

Rare disease aren’t so rare. The definition of a “rare disease” varies by country, often based on laws that dedicate funds to their research or ease the approval path for new treatments. In the U.S., the standard is a condition that affects fewer than 200,000 people. In the EU, it’s a condition that affects less than one person in 2,000. Based on those differing standards, 25-30 million people in the U.S. have a rare disease, and an equivalent number in the more populous EU. Anne Pariser, who directs the Office of Rare Diseases Research at the U.S. National Institutes of Health, says about 8% of the global population has a rare disease — about 350 million people.

The vast majority of rare diseases have a genetic origin. About 85% of rare diseases are genetic — generally “single gene” disorders caused by a mutation or a defect in a single gene. Those genes should code for a normal cellular biologic process — but something has gone wrong. “You can think of these as housekeeping genes that keep us healthy and up and running,” Pariser said. But changes in even one base pair on one of those genes can have profound effects, she said. Other rare diseases can be caused by environmental exposures, poisonings and even snake bites.

Only 5% of rare diseases have an approved therapy. The reason is simple: It’s hard to make a profit from treatments that benefit few patients. The majority of rare diseases are really, really rare, affecting fewer than 3,500 patients. Just 10% of rare diseases affect 90% of rare disease patients, and 90% of rare diseases affect 10% of the patients. “We do have diseases that what we know now can affect 10 or fewer patients,” Pariser said.

Precision medicine and other breakthroughs offer new hope “The good news is rare diseases are really a model for precision medicine,” Pariser said. That approach — also known as targeted or personalized medicine — allows physicians to target smaller and smaller populations based on their understanding of a patient’s genetic structure. One example: A precision medicine approach uses “anti-sense oligonucleotide” to target tiny pieces of RNA to a patient’s particular gene mutation. Pariser described how the process helped a 3-year-old girl with a very rare form of Batten disease, a neurodegenerative genetic disorder that has always been fatal. The approach appears to have stopped the disease in the girl. It was a remarkable achievement, Pariser said — but also one that came with a hefty price tag: $2 million. “That raises the question of, how do we do more of this?” she asked. “How do we do it faster, and how do we do it for more people?”

Speaker: Anne R. Pariser, Director, Office of Rare Diseases Research, National Center for Advancing Translational Sciences, U.S. National Institutes of Health

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