by Amanda Zink, J.D., M.A. and Jill P. Buyon, M.D.

As national funding decreased in recent decades, medical research suffered. Progress toward uncovering beneficial preventative and therapeutic treatments slowed for thousands of devastating conditions, affecting the health, happiness, and life expectancy of millions of Americans. Young scientists trying to enter the biomedical research arena last year faced the worst funding climate in half a century, with NIH spending down 22% since 2003. December of 2015 brought a glimmer of hope, however, when Congress passed a federal spending bill that included the biggest increase in NIH funding in 12 years, an additional $2 billion that NIH Director Francis Collins says came at “just the right time to take advantage of remarkable opportunities to improve human health, powered by dramatic advances in scientific knowledge and technological innovation.”
Today might be considered “rare” because it is a Leap Day. But it also Rare Disease Day, a global movement that seeks to raise awareness and promote advocacy for diseases that have fallen under the radar screen simply because they are considered rare.

“Rare” can engender many different connotations. It can mean something positive, like winning the Powerball jackpot, or it could refer to the dangerously low count of an exotic species, like a snow leopard, which has become so endangered that tremendous resources are poured into maintaining its survival. However, “rare” to someone with a medical affliction can translate to uncertainty and despair.

Jill Buyon, a medical doctor with a major focus on translational research and the Division Director of Rheumatology at NYU Langone Medical Center, has devoted her career to uncovering the cause and prevention of a rare disease known as neonatal lupus.

About one in 200 women carry antibodies to certain proteins called SSA/Ro and SSB/La. Two percent of these women face the chance of having a child with a life-threatening heart condition known as congenital heart block (CHB). In children with CHB, the heart beats at an abnormally slow rate, and the vast majority of children require permanent pacemakers before the age of 20. Sadly, however, nearly one in five die before birth or shortly thereafter.

The disease is thought to occur in only 1:15,000 births, but “rare” does not matter when it happens to you – or your baby.

In 1994, with the help of NIH funding, Dr. Buyon founded the Research Registry for Neonatal Lupus and it has generated the bulk of evidence-based information on this rare and devastating disease. The Registry has been an invaluable resource for both bench science research and for clinical trials aimed at uncovering preventative treatments and effective therapies.

The ongoing NIH-funded PATCH trial, currently in Stage 2 after successful completion of Stage 1, seeks to determine whether the use of hydroxychloroquine during pregnancy prevents the recurrence of CHB. Amanda Zink has a background in law and bioethics and has been working with PI Dr. Buyon on the regulatory, financial, and bioethical aspects of the PATCH study since its inception.

If the PATCH study yields a positive result, it could justify screening all pregnant women for these critical antibodies going forward, potentially improving the management and outcome of these pregnancies. This could also improve the overall health of the mothers, since most women only find out they possess the antibodies based on disease in an offspring, but more than half go on to develop an autoimmune disease such as lupus or Sjögren’s Syndrome. While there is no cure for lupus, early detection and treatment are crucial to help manage symptoms and reduce the likelihood of permanent organ damage. This study is an example of how rare disease research can have implications and benefits that extend far beyond the impact on the rare disease itself.

Advances in genetic analyses also underscore the importance of research into rare diseases, which can often be traced to genetic mutations. The NIH’s 2016-2020 strategic plan places paramount importance on rare disease research since it is not only needed to help rare disease sufferers, but frequently leads to general physiologic insights that affect us all. For example, molecular studies into progeria, a rare disease that causes premature aging, have uncovered valuable insights into the way we all age. Similarly, discovery of the role of the BDNF gene in a disease called WAGR syndrome, which affects as few as one in one million individuals, has led to striking evidence of the role of this same gene in obesity, which affects a full one-third of U.S. adults. The genetic basis for these diseases can also lead to devastating circumstances due to the heritability of a mutation, such as when Kristen and Gordon Gray discovered that both their young daughters had an incurable disease called Batten that would kill them by age 12 short of a miraculous treatment discovery.

Given the need to prioritize in this difficult funding climate, researchers of lesser-known conditions are losing grant support to those studying more common diseases like cancer. But while a disease is deemed “rare” if it affects fewer than 200,000 people, it is somewhat misleading given that there are over 6,800 rare diseases that affect a total of 25-30 million Americans. It is not rare to suffer from a rare disease.

In Dr. Buyon’s decades as a researcher in neonatal lupus, she has had the great privilege of helping hundreds of women manage their pregnancies, using the best available evidence to maximize maternal and fetal health. She has also had to counsel countless women who have experienced the loss of a pregnancy or the death of a child. With sufficient public demand and adequate funding, we can make every day Rare Disease Day – until we’ve uncovered the “miracles” needed to save the millions of patients and family members who rely on us as their only hope.

Acknowledgments: The authors thank Mona Lisa Mouallem for encouraging us to highlight our research and the many families affected by neonatal lupus on Rare Disease Day, and for editorial assistance with this piece.