What rare diseases can teach us
THIS SUMMER, 8-year-old Jessica Leoni was admitted to UCLA Medical Center for treatment of seizures brought on by a rare neurological disease called Niemann-Pick Type C, or NP-C. After 11 days, her doctors finally identified a drug that could control her seizures, and she returned to her Westchester home with her relieved parents.
But this family’s relief is bound to be tempered by the knowledge that there is no known cure for NP-C and, because it is so rare, research to find a cure is badly underfunded.
And NP-C is only one of about 6,000 such diseases, identified by the National Institutes of Health as ailments that each affect fewer than 200,000 Americans.
Both the government and private drug companies too often look at such numbers and say no to the funding required to finding treatments and cures. But that traditional calculus is incomplete -- there are plenty of good reasons to do more to fund rare-disease research.
First, even rare diseases affect a huge number of people. Nearly 25 million Americans suffer from one of the conditions that the National Institutes of Health lists as rare.
The financial and emotional burdens on our society of not adequately treating such illnesses are immeasurable.
In addition, however, such research also has ramifications far beyond the individual sufferers. Rare diseases represent unique windows that allow scientists to peer into the intricate workings of our bodies.
Indeed, 3 1/2 centuries ago, long before the initiation of the human genome project and other riches of modern medicine, the leading physician of his day, William Harvey, implored his colleagues to carefully investigate the rarer forms of disease in order to advance the proper practice of medicine.
Harvey’s prescient view was that determining what was missing or altered in an uncommon disease could inform us as to its importance in the normal human body.
Harvey’s reasoning remains as sound today as it was in 1657.
Consider, for example, Fragile X syndrome, a leading cause of mental retardation and autism that, according to the Centers for Disease Control, affects 1 in 4,000 boys and 1 in 8,000 girls in the United States. This condition has been linked to a defect in one gene on the X-chromosome that codes for a protein, FMRP, believed critical for transporting genetic messages in brain cells. Without the protein the brain looks normal but learning and memory are severely impaired.
Scientists believe that studying Fragile X will lead to the discovery of how the nervous system normally stores information -- still one of the brain’s great mysteries -- and by fully understanding how this protein facilitates learning, we may be able to help not only patients with Fragile X but also those with other, unrelated forms of mental retardation.
Researching diseases such as NP-C could be similarly illuminating. Brain cells in children with this disease are characterized by the formation of abnormal “tangles” that are identical to those of adults with Alzheimer’s disease, though the diseases are not otherwise closely related.
Drugs developed to control NP-C disease could provide critical clues for controlling the progression of tangle formation and neuron death in Alzheimer’s.
Perhaps the most shortsighted aspect of marginalizing the so-called rare diseases is that they really may not be so rare. Instead of adding up the numbers based on how many sufferers there are for each disease, we should do the calculations recognizing the commonalities among them.
Once again, NP-C is a good example. It is what is known as a “lysosomal storage” disease -- one that involves a tiny structure in cells known as the lysosome. There are nearly 60 types of lysosomal diseases known today -- such as Gaucher, Krabbe, Sanfilippo and Hurler. Individually they may affect fewer than 100 patients, but as a group, lysosomal diseases are estimated to occur in about 1 in every 7,500 live births, a frequency midway between two of the best-known “rare” diseases -- cystic fibrosis and phenylketonuria, or PKU.
Knowledge gained by the study of one of these diseases is highly likely to provide insight into others in the group.
Many rare diseases, including those in the lysosomal group, begin in childhood, which means that research leading to corrective therapies could rescue individuals from a fate that may include seizures, blindness, mental retardation or dementia and death, often after decades of declining health. Such research would also lessen the burden that long-term diseases place on our society as a whole.
In the past, rare diseases have remained singular tragedies, but as information sharing has gotten easier with the Internet, families with rare diseases are discovering one another. They are joining forces to lobby for a different view of the costs and benefits of adequately funding rare-disease research.
This can be seen through the growth of organizations such as the National Organization of Rare Diseases and the Genetic Alliance, as well as smaller groups dedicated to finding treatments and cures for individual rare diseases.
Significantly, new coalitions are also emerging, as is the case with lysosomal diseases, where umbrella groups such as the Hide & Seek Foundation, based in Los Angeles, and the Global Organization for Lysosomal Diseases have been formed.
These organizations dedicated to finding treatments and cures for individual rare diseases have a simple message: Investment in research on rare diseases clearly pays dividends on many levels and benefits us all.
Certainly the simplest of calculations -- the one that tells us which diseases affect the fewest Americans -- shouldn’t be the main determinant controlling how we spend our research dollars.
STEVEN U. WALKLEY is a professor of neuroscience at the Albert Einstein College of Medicine in New York.
