Born under atypical circumstances, a perfect storm wields unimaginable havoc. So, does a rare disease. What exactly constitutes a rare disease? In the U.S., the Orphan Drug Act of 1983 stipulated that “rarity” meant the disease affected fewer than 1 in 200,000 people, which applies to about 7,000 diseases (National Institutes of Health, 2017). With so many rare diseases, the NIH estimates that as many as 20 to 35 million Americans suffer from one of the ~7000 rare diseases, which is about 1 in 10. That means you likely know a person caught up in a not-so-rare perfect storm.
What makes a rare disease a perfect storm? Well, like a meteorological perfect storm, a unique combination of events transpires. Those afflicted with one of the roughly 7000 named biological storms hit the trifecta of difficulty in getting a correct diagnosis, finding a doctor knowledgeable of the disease and securing some type of treatment plan. Despite the good intent of the Orphan Drug Act of 1983, affordable treatments can be as rare as the disease itself. The rare disease not only challenge the actual patient, but also the doctors and researchers (Stoller, 2018).
Unlike the meteorological version, we have a shot at taming the biological perfect storm through new medical insights and improved communication. So, let us break out a new kind of powerful Doppler radar: proteomics. Yes, proteomics can reveal a lot about us and even potentially help people weather their particular storms.
Looking at Castleman disease, we can see proteomics in action (Pierson et al., 2018). This very rare and devastating disease involves enlarged lymph nodes and can be subdivided into one of three categories depending on symptoms and presence of a viral infection. One of these subgroups — Human Herpesvirus (HHV)-8-negative, idiopathic multicentric Castleman disease (iMCD) — wields extremely severe symptoms, can be fatal, arises from unknown origins and is difficult to treat. Dr. David Fajgenbaum and co-researchers used proteomics to tease out the details of iMCD, which can be further subdivided into two groups. They mentioned that initially it was thought that cytokines were the driving force behind iMCD, with interleukin-6 playing a significant role. However, only a third of patients responded to anti-interleukin-6 therapy. Through the proteomics, the researchers saw that the two subgroups of iMCD had two different proteomic profiles. This difference might explain why one group did not respond to anti-interleukin treatment and the other one did. Also, they found that although cytokines do play a part in the perfect storm, it is really a smaller group, chemokines (proteins that direct white blood cells to sites of infection) that are at the eye of the storm.
Just think, we maybe be witnessing the potential for calm after this storm! One day, we could have the means to determine quickly and accurately who may benefit from certain treatments. This work has also highlighted new targets for therapeutics or new potential treatment strategies. The proteomic Doppler radar could be our deliverance from the havoc wreaked by the perfect storm of rare disease.
National Institutes of Health/ National Center for Advancing Translational Sciences/ Genetic and Rare Diseases Information Center. (2017, November 30). FAQs About Rare Diseases. Retrieved on July 12, 2018 from https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases.
Pierson, S. K., Stonestrom, A. J., Shilling, D., Ruth, J., Nabel, C. S., Singh, A., . . . Fajgenbaum, D. C. (2018). Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease. Am J Hematol, 93(7), 902-912. doi:10.1002/ajh.25123
Stoller, J. K. (2018). The Challenge of Rare Diseases. Chest, 153(6), 1309-1314. doi:10.1016/j.chest.2017.12.018