On Rare Disease Day, Remember What Family Organizations Can Do

Families who receive a new rare disease diagnosis face seemingly insurmountable challenges. The basic questions that come from any diagnosis, like “what does this mean?” “What is the treatment?” “What should we expect?” are often not known to even the doctors and nurses involved. Learning of a diagnosis for which very little is known and very little research is being done can be isolating. A feeling of being alone is a common reaction, and the idea that there is really nowhere to turn. But as genetic results have become more and more precise and social media has become more a part of everyday life and international in scope a lot of that can change. Families can connect and organize around a rare disease that is shared by a group. They can share experiences, find help, connect with doctors and researchers interested in their condition. They can meet, organize, and raise funds and support for research which they then can drive forward.

This is not hope for the future, this is happening now. In our example, the Global Foundation for Peroxisomal Disorders (GFPD) started as a family email group (with 40 families) in the early days of the internet and grew to a nonprofit public charity in 2010 now serving over 400 families in 39 countries around the world. The GFPD supports families through online support groups and medical and educational advocacy. Additionally, the GFPD supports and funds groundbreaking research that could lead to potential treatments for peroxisomal biogenesis disorders. Peroxisome Biogenesis Disorders (PBD) are a rare group of genetic disorders in which an individual cannot properly produce peroxisomes inside their cells. The peroxisome, a tiny biochemical factory helps us regulate and/or produce a number of specialized fats and other molecules. Without the peroxisome these molecules are thrown out of balance. These disorders cause severe symptoms, particularly affecting the brain, and there are no good treatments. Research into these complex disorders is carried out by relatively small groups of academic physicians and scientists.

This week the results of just one of the many research studies underway driven forward by the GFPD was published online and will be in an upcoming issue of the Nature Publishing group journal, Genetics in Medicine. This paper provides a metabolomics or “small molecule roadmap” of how PBD can affect the chemistry of the bloodstream. A unique characteristic of this study was the partnership between the GFPD and researchers. How was this study achieved? One of us, a physician in medical genetics had treated a family with an individual affected by PBD, and had become inspired (See Peroxisomes and sugar metabolism) to work on the disorder and had been researching the small molecule maps, using animal models. This research had pointed to several pathways but how did the animal models compare with real patients? Would the map have any utility in patients with PBD? Through a unique laboratory effort the possibility of a human study was there. But initially the only participants were families receiving care at Texas Children’s Hospital.

That’s where the GFPD allowed this research to be expanded to more families. One of us (Gamble) has seen the GFPD has grown into an international organization with over 400 families worldwide, with robust research resources, a scientific advisory board spanning the globe, biennial family and scientific meetings, regional family meetups, and a wide variety educational and medical supports for families facing Peroxisomal Biogenesis Disorders.

One of us (Bose) is both a parent and a research scientist. Having this dual point-of-view, we were able to comprehensively explain to families why they should participate in this study, what families hope to gain from an exploration like this, and answer any questions participating in research, from both a caregiver and a researcher perspective.

Indeed these efforts led to a successful study of a rare disease using metabolomics technology, with 19 participants. There are three major initial outcomes from this research. First, it seems PBD produces a recognizable pattern on metabolomics and other patients can be flagged for potential PBD diagnosis using metabolomics. Second, it seems that while young children with PBD have a clear small molecule profile, older subjects somehow normalize these changes. Why the metabolomic findings appear to normalize in older subjects is not currently known. There could be some compensation or effect of growth or aging that remains unexplored. Third, another lipid, sphingomyelin, seems to be unexpectedly low in PBD. This particular finding is novel and just beginning to be explored. The fact that sphingomyelins are a key component of myelin and and neuronal and white matter changes are a characteristic of disease make this finding intriguing.

As an example, the work of the GFPD is advancing research. But what about families with another of the thousands of rare disorders? What about the public and convincing them that PBD and other rare diseases are important. When the Rare Diseases Act of 2002 was passed, it supported initiatives that encouraged physicians, scientists AND patients to work together to make strides in rare diseases. This was largely with the tremendous impact that rare disease studies can have on larger public health questions (See, for example our Top Ten Rare Disease Papers of All Time). Indeed, PBD have pointed to fundamental brain chemistry that is altered in Alzheimer’s disease, and genes implicated in PBD are also linked to obesity in the population. These and other emerging examples make rare disease research of paramount importance.

While this study, one of many involving the GFPD is only one example, and is preliminary insight to us it is an example of families, and scientists working together and driving rare disease research forward.

By Michael Wangler, Mousumi Bose and Melissa Gamble
Posted in Uncategorized.