Photo of Atul Chopra

Q&A with a researcher who studies rare diseases

In 2012, physician-scientist and medical geneticist Atul Chopra met two patients with an extremely rare disease: marfanoid progeroid lipodystrophy (MPL). Known to cause extreme leanness in patients, the disease, Chopra believed, could also hold the key to one of the most enduring health challenges facing Americans: obesity. 

There are only 20 documented cases in scientific literature of patients with MPL, which leaves those affected with a very low appetite and a body-mass index in the 9–13 range (compared with the typical 18–25). But despite this rarity, Chopra was determined to discover what drives the disease.

The answer? A genetic mutation that doesn’t allow patients’ bodies to produce enough of a previously unknown hormone Chopra’s lab named asprosin. As the researchers gained a deeper understanding of asprosin, they realized those with obesity overproduce the hormone.

“So, that’s brought the story full circle—we discovered a brand-new hormone by studying two patients with an ultra-ultra rare disease, and have used that information to attempt developing a drug for diseases that affect millions,” Chopra explained. “That’s the power of rare disease research!”

MPL is just one of more than 7,000 rare diseases identified by the National Institutes of Health, impacting an estimated one in 10 Americans. The U.S. defines a rare disease as one that is found in fewer than 200,000 individuals. 

Each year, Rare Disease Day (Feb. 28) helps bring attention to these conditions. To champion the important work medical researchers conduct at Case Western Reserve University School of Medicine and beyond , The Daily spoke with Chopra about his research and why studying rare diseases is so important.

Q: Why did you decide to specialize in rare diseases?

I am driven by medical and scientific mysteries. Rare diseases offer the chance to solve both types of mysteries. I find rare diseases with extreme manifestations, like [MPL], very powerful when it comes to discovering brand new biological information. It’s sort of like a supercharged discovery wand. It is exhilarating and it offers a chance to help people with all kinds of diseases—rare and common.

Q: What do you think more people should understand about rare diseases?

It is not well appreciated that the thousands of rare diseases are rare individually, but together as one entity affect a large percentage of humanity. I also think it is not well appreciated that the study of rare genetic diseases provides a window into nature—how it is supposed to work and how it has broken down—with unprecedented clarity. 

Q: What do you ultimately hope to accomplish through your work on rare diseases?

Simple: (a) discover tons of new biology with an emphasis on “new,” and (b) develop drugs for all kinds of diseases by using the newly discovered information. Goal (b) is very dependent on goal (a), and the process depends on our ability to discover. 

Q: Do you work directly with patients, or have you in the past? If so, what was that experience like?

I work directly with rare disease patients by directing a clinic at University Hospitals called the Clinic for Disorders of Energy Balance. I see patients with extreme leanness on one end of the spectrum, like the MPL patients described above, and patients with extreme obesity and diabetes on the other end of the spectrum. Most of my patients are kids because these diseases show up early. 

The experience is gratifying, and I always have it in the back of my head that my patients can most benefit not only from the care I provide clinically, but from our discovery work leading to new medicines.