When you choose to publish with PLOS, your research makes an impact. Make your work accessible to all, without restrictions, and accelerate scientific discovery with options like preprints and published peer review that make your work more Open.

PLOS BLOGS PLOS SciComm

The Importance of Research on Rare Diseases

This post features work by an undergraduate student at Indiana University Purdue University Indianapolis. Kesha Bhatt has been working with us throughout the academic year to enhance her skills for communicating science to the public. In this piece, she emphasizes the importance of studying rare diseases as a window to understanding more common diseases. In particular, she focuses on cerebroatrophic hyperammonemia (CH), also known as Rett Syndrome. We have chosen to refer to this rare disease as CH throughout the piece because Andreas Rett, for whom Rett syndrome is named, has a checkered past. Rett (1924-1997) was born in Bavaria but his family moved to Innsbruck, Vienna, when he was five years old. At the age of 18, Rett joined the Nazi Party in Innsbruck, and after two semesters in medical school he was recruited to the German Navy, where he served until the end of World War II. He returned to Innsbruck to complete his medical training but was initially denied reentry to the university because of his active participation in a leadership role in the Hitler Youth organization. He was ultimately allowed to finish his studies after he issued a (fabricated) statement that he had no active or previous affiliation with the Nazi Party or the Hitler Youth. Documentation indicates that this statement is false, and Rett never acknowledged his past or disavowed any Nazi views. For this reason, we choose to acknowledge CH without referencing the physician who described the syndrome. More information on Andreas Rett can be found here. –JMO

 

by Kesha Bhatt, Life-Health Sciences Intern, IUPUI

 

Cerebroatrophic hyperammonemia (CH) is a rare genetic disorder caused by the mutation of the MECP2 gene. The disease is prominent in females and the common clinical signs and symptoms include microcephaly (head circumference is smaller than normal), loss of coordination and normal movement, loss of communication abilities, abnormal hand movements, breathing problems, cognitive disabilities, irregular heartbeat, sometimes seizures, and Scoliosis (abnormal curvature of the spine). People living with this disease first experience the gain of motor skills and the ability to speak, however, they also see that ability go away just as quickly.

Beth Johnson’s daughter, Hannah, suffers from CH. Beth shares her heart wrenching story about the pain her daughter and the entire family experiences on a daily basis. When she was three years old, and after months of testing, Hannah was diagnosed with CH. The day Beth found out, she “left the hospital in pieces and knowing that things would never be the same” (Jupp, 2013). CH affects not only the patient, but the entire family. Hannah knows that she has a severe disability and her deteriorating ability to use her hands and feet causes frustration. The only two words she is able to say are “Mummy” and “Daddy” (Jupp, 2013). Beth mentions how Hannah “often gets frustrated and she sinks her nails into your skin and screams—it’s her only method of communication” (Jupp, 2013). Hannah doesn’t intentionally try to cause harm to those who love her, however the frustration this six-year-old girl faces, is beyond imaginable.  It is heartbreaking for them to know that there is no cure. Beth says, “I go through anger and denial on a daily basis, but I will not accept and I don’t think I ever should when…there is still so much hope” (Jupp, 2013).

There are over 25 million people in the US who face daily battles with rare diseases like CH. Although a disease like CH may only affect 1/10,000 to 1/22,000 females in the US (and rarely any males), there are 7,000 other rare diseases that affect millions of other people. Because these diseases are rare, we do not know as much about them as we do other, more common diseases. This creates problems in management of rare diseases because it leads to misdiagnosis, unmet treatment, and lack of medication. It is critical that people understand the importance of funding for rare disease research.

Even when a rare disease is diagnosed, “95 percent of rare diseases have no Food and Drug Administration approved treatment” (Slade et el., 2018). Rare diseases only affect a few people compared to common diseases, and therefore receive less funding for research—more common diseases receive more funding because they affect more people and therefore more people stand to benefit from the research.

The lack of funding results in a lack of treatment options, clinical trials on new treatments, and development of novel medications. Patients with rare diseases that have no cure or FDA-approved treatment options have to settle for treatments that manage the symptoms of the disease instead of treatments that can address the underlying problem. For example, the annual cost for those living with CH ranges anywhere from $238 to $85,776 per year. This includes long-term residential care, therapy care services out of school, and paid home and community care (Hendrie et el., 2010). Another rare disease, Hemophilia, can cost about $131,111 annually. The average household income in the United States is $89,930.70, just about $4,154.70 more than the annual cost of for treating CH or $41,180.30 less than the annual cost for treating Hemophilia (Rare Disease Day, 2018). Some patients with rare diseases have also have the obstacle of frequent and long travel to consult physicians with previous experience in treating and studying the rare disease. It is critical that we increase funding for rare disease research because while any given rare disease may only affect thousands or tens of thousands of individuals, collectively, rare diseases affect 25 million Americans.

How can research on rare diseases possibly be useful to the research on common diseases? According to Elizabeth Burke, PhD, a postdoctoral fellow in the NIH Undiagnosed Diseases Program and researcher of genetic variants causing rare diseases, researching rare diseases could lead to the discovery of previously unknown gene functions, which could be helpful in developing treatment strategies. Additionally, understanding the roles of genes in rare diseases may enhance “our understanding of related common diseases.”

According to the Progress in Rare Diseases Research 2010-2016, “many rare diseases resemble common ones and involve the same genetic pathways.” In fact, some rare diseases may be severe versions of more common diseases. This is why researching rare diseases will potentially provide more information and insight into the development of research for common diseases.

Research has shown that the MECP2 gene—a gene involved in regulating gene expression to avoid excess production of proteins in brain cells—is involved in many neurodevelopmental disorders and “it occupies a central role in the postnatal development of the human brain” (Gonzalez 128). If the MECP2 gene loses its function, meaning it loses control over the amount of MECP2 protein that gets produced, then the body will continuously produce those proteins, which can damage the nervous system and result in CH.

Researchers have also confirmed that the MECP2 gene may also play a role in patients with autism. They believe that “autism spectrum disorders may have a genetic defect that reduces their brain’s expression of MECP2 protein” (U.S. Department of Health and Human Services). The genetic component of autism is unclear and is thought to involve numerous genes. However, “mutations in MECP2 identical to some classic [CH] mutations have been identified in a small number of autistic females” (Gonzalez and La Salla, 2010: 129-130). The MECP2 gene has multiple functions in the brain. Therefore, research on rare diseases is important because it can lead to the discovery of other components that may be affecting common diseases and aid in developing effective medications.

With the recent marking of Rare Disease Day on February 29, 2020, it is a good time to remind ourselves why supporting research on rare diseases is important not just for patients of these disease but for patients of more common diseases that may have a close connection to the biology of rare diseases too.

 

 

References:

Slade, Anita, et al. “Patient Reported Outcome Measures in Rare Diseases: a Narrative Review.” Orphanet Journal of Rare Diseases, vol. 13, no. 1, 2018, doi:10.1186/s13023-018-0810-x.

Hendrie, Delia, et al. “Measuring Use and Cost of Health Sector and Related Care in a Population of Girls and Young Women with Rett Syndrome.” Research in Autism Spectrum Disorders, vol. 5, no. 2, 2011, pp. 901–909., doi:10.1016/j.rasd.2010.10.004.

Dawkins, Hugh J.s., et al. “Progress in Rare Diseases Research 2010-2016: An IRDiRC Perspective.” Clinical and Translational Science, vol. 11, no. 1, 2017, pp. 11–20., doi:10.1111/cts.12501.

“Rett Syndrome: Research Activities and Scientific Advances.” Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. Department of Health and Human Services, 1 Dec. 2016, www.nichd.nih.gov/health/topics/rett/researchinfo/activities#f7.

Jupp, Emily. “Rett Syndrome: ‘Hannah Is Painfully Aware of Her Limitations’.” The Independent, Independent Digital News and Media, 9 Apr. 2013, www.independent.co.uk/life-style/health-and-families/features/rett-syndrome-hannah-is-painfully-aware-of-her-limitations-8564928.html.

Gonzales, Michael L., and Janine M. Lasalle. “The Role of MeCP2 in Brain Development and Neurodevelopmental Disorders.” Current Psychiatry Reports, vol. 12, no. 2, 24 Mar. 2010, pp. 127–134., doi:10.1007/s11920-010-0097-7.

“Rare Disease Day 2018: The Importance of Funding and Research.” Multiplesystematrophy.org, 6 Feb. 2018, www.multiplesystematrophy.org/uncategorized/rare-disease-day-2018-importance-funding-research/?gclid=EAIaIQobChMIrZzH3IvH5wIVTb7ACh1GIwrZEAAYASAAEgJglfD_BwE.

 

 

 

Kesha Bhatt is a student at IUPUI on the pre-med track majoring in Biology and minoring in Spanish and Chemistry. Her goal is to go to medical school to pursue a career in the medical field as either an obstetrician or family physician. With learning and completing a minor in Spanish, she is proud to have expanded her knowledge of languages from three languages (English, Hindi, and Gujarati) to four.

 

 

 


Want to stay connected with #SciCommPLOS or pitch an idea for a blog post? Tweet us at @SciCommPLOS or email us at scicommplos@gmail.com.

Leave a Reply

Your email address will not be published. Required fields are marked *


Add your ORCID here. (e.g. 0000-0002-7299-680X)

Back to top