Rare diseases are not rare — and treatments are coming

Eight percent of Americans name apples as their favorite fruit. About 5 percent of the world population owns a computer and 7 percent are on Facebook. Nine percent own a car. Only 2 percent of adults are natural blondes.

Yet 10 percent of people on this planet have a rare or “orphan” disease. In the U.S., that’s almost 30 million people.

Approximately 7,000 medical conditions have been identified as “rare” – defined by the Orphan Drug Act, passed in 1983, as affecting fewer than 200,000 people in the U.S. Some of these are relatively well known and well studied, such as sickle cell disease or amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease); each affects roughly 30,000 patients in the U.S. Others – like multiminicore myopathy, Diamond Blackfan Anemia or galactosemia – you’re unlikely to have heard of, because they affect only a few hundred or thousand people.

Most of these diseases affect children, often from birth, so at pediatric hospitals, patients suffering from something rare and understudied are actually very common. These disorders are medically serious conditions, often leading to an early death in infancy or childhood, or severe debility throughout life.

When I started my scientific career in the 1980s, only a handful of rare genetic conditions were understood. Over the past decade, my laboratory alone has been involved in discovering more than a dozen rare disease genes, many of them for muscle-weakening disorders, and the total number of known disease genes has skyrocketed to more than 3,000.

Here in Massachusetts, we’re blessed with one of the greatest concentrations of research and commercial development expertise anywhere in the world. Both are starting to focus more on rare diseases – not just because of the many children and adults suffering from them, but also because discoveries about rare diseases often have implications for much more common conditions.

In the early 1990s, for example, scientists at the Dana-Farber Cancer Institute, Children’s Hospital Boston and Massachusetts General Hospital discovered that mutations of a gene called p53 caused an extremely rare familial cancer disease called Li-Fraumeni syndrome. As it turns out, p53 is spontaneously mutated in almost half of all cancers in the general population.

The movie Extraordinary Measures tells the story of a father who worked with a scientist to find a cure for his two children with Pompe disease, a lethal condition that prevents the body from breaking down sugar. His quest led to the 2006 FDA approval of a replacement enzyme called Myozome, marketed by Genzyme.

Increased understanding of these disorders has started to revolutionize patient care. Methods of enzyme replacement, pioneered by companies such as Genzyme, with the help of academic physicians from centers like Children’s Hospital Boston, have revolutionized the care for thousands of patients worldwide with various lysosomal storage diseases. This has turned often progressive and fatal diseases – like Gaucher disease and Pompe disease – into manageable chronic conditions, potentially adding decades to children’s lives. This approach of enzyme replacement, popularized by movies like Extraordinary Measures, is now a well-recognized method of treating many deadly diseases.

Recent technical advances are making it easier than ever to discover the causes of many rare diseases. New machines allow us to sequence a person’s entire genome in a matter of weeks, at a cost of a few thousand dollars – compared to 10 years and $2.7 billion for the very first genome sequence in the 1990s. The strong partnership between academics and biotechnology in Massachusetts is driving these discoveries ever faster towards treatments and cures. Here at The Manton Center for Orphan Disease Research, our Gene Discovery Core serves as an international clearinghouse for applying the latest genetic technologies to the very rarest, least understood of diseases.

Rare Disease Day, this year designated as February 29th, 2012, is a fitting tribute to all the progress that we have made, and a call to action for all the work that remains to be done. Locally, the Massachusetts Biotechnology Council is hosting an event where I’ll be speaking along with a rare disease patient, leaders of patient foundations, legislators and ranking representatives from Genzyme and Pfizer. It’s an opportunity to increase public awareness and, we hope, research funding from both federal and philanthropic sources.

I am heartened by the dramatic progress we’ve made – and confident that we can make further strides towards improving the lives of children and their families afflicted by diseases both rare and common.

Alan H. Beggs, PhD, is Director of The Manton Center for Orphan Disease Research at Children’s Hospital Boston and the Sir Edwin and Lady Manton Professor of Pediatrics at Harvard Medical School. His laboratory in the Genetics Division of Children’s Hospital Boston focuses on the study of rare muscle diseases called congenital myopathies.