The Importance of Research on Rare Diseases – Innovita Research

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 goes away just as quickly.

Image credit: via PLOS

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 the 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 al., 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 the 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 had 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, Ph.D., 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, it is a good time to remind ourselves why supporting research on rare diseases is important not just for patients of this disease but for patients of more common diseases that may have a close connection to the biology of rare diseases too.

Source: PLOS EveryONE. written by Kesha Bhatt