Rare Disease Research Opens Many Doors

Rare diseases are a paradoxic — they are both uncommon and common. And understanding them may help us to gain insights into more ordinary diseases. 

If a disease affects fewer than 200,000 people in the United States, it is considered a rare disease. But there are an estimated 5,000 to 8,000 rare diseases. In a country with 329.5 million people, this means roughly 1 in 10 Americans likely has a rare disease.1 And more than 300 million people globally are estimated to live with a rare disease.2 

While each rare disease may be an individual rarity, having a rare disease is more common than one may think.1 As genomic techniques advance, it is expected that the actual number of known rare diseases may expand to more than 10,000.3

Rare diseases, burdens and types

Of the thousands of known rare diseases, only about 300 have an approved treatment.1 This unmet need presents a rich opportunity for research. But because rare diseases affect few people by definition, they tend to get short shrift in research funding. 

This ripples into a lack of clinical trials, a dearth of novel treatment options, plus increased health care costs and resource use for those who are living with a rare disease.4 The economic burden of rare diseases is estimated to range between $400 — $768 billion in direct medical costs.5 Developing new treatments would help relieve individual financial strains, but also the strain on our health care systems.

Most rare diseases are caused by specific genetic variants, but they can take other forms. For example, some rare diseases are cancers, autoimmune diseases, or infectious diseases.6 No matter their origin, they pose similar clinical challenges because most physicians are unfamiliar with diagnosing or managing rare diseases.3

The potential of rare diseases

Research into rare diseases may yield expansive benefits beyond those who live with them. This is because sometimes the same genetic pathways are involved in multiple rare diseases, or between a rare and a common disease. Investigating the underlying genetic features of a rare disease may also uncover previously unknown gene functions, which could benefit common diseases and health conditions.4

Take Rett syndrome, for example. This is a condition caused by a mutation of the MECP2 gene. Proteins made by this gene are abundant in the brain where it promotes neural activity and is thought to assist in maintaining connections between neurons via synapses.7 People with Rett syndrome experience a damaging overproduction of MeCP2 proteins. 

This condition mostly affects girls and first appears in childhood. Children with Rett syndrome who learn to walk and talk soon lose these abilities. They experience neurodegenerative symptoms such as loss of purpose-driven use of their hands, seizures, and delays and declines in conscious mental activity.8

But the MECP2 gene is also involved with several other conditions, some of which are more dominant in one sex or the other. Genetic changes in this gene have been found in some females with autism9 and in PPM-X syndrome, which affects males more than females.9 But MECP2-related severe neonatal encephalopathy10 and MECP2 duplication syndrome only affect males.11 Better understanding the MECP2 gene could benefit people who live with all of these conditions. 

Therapies for rare diseases

Economics are often cited as a primary obstacle for developing new therapies for rare diseases. High costs of developing drugs or biological products and bringing them to market can prevent pharmaceutical companies from moving forward when they anticipate a small market for sales, and limits on their return on investment.12

Another challenge is the high cost of gene therapies, which are a potential platform for many rare diseases with underlying genetic causes. Additional barriers include long development times due to the need to expand existing knowledge and build natural history databases., and extending recruitment timelines for clinical trials given the limited pool of people who may meet inclusion criteria.12  

Despite these challenges, there is much room for optimism. Gene therapies are gaining traction and success in many diseases. These include gene transfers using viral vectors, disruptive gene therapies such as antisense oligonucleotides, RNA interference and micro-RNA modulators to change or obstruct a protein involved in the disease. Gene-modified cell therapies and gene editing techniques are also showing promise.12 

The national government is also supporting rare disease research through several different programs. The National Center for Advancing Translational Sciences, a part of the National Institutes for Health (NIH), operates a program to  catalyze research on rare diseases called the Therapeutics for Rare and Neglected Diseases.13

A separate partnership between the NIH and the Food and Drug Administration plus several private groups, the Bespoke Gene Therapy Consortium (BGTC), also seeks to speed the development of therapies for those with rare diseases. By developing a therapeutic platform for treating rare diseases, the BGTC aims to support development of therapies for many different diseases all at once.14




  1. National Institutes of Health. NIH Rare Disease Day. Available at https://irp.nih.gov/catalyst/v23i3/nih-rare-disease-day. Accessed 3/15/2022. 
  2. Imhoff J. 10 Studies That Highlight the Importance of Rare Disease Research. University of Michigan Health Lab. Available at https://labblog.uofmhealth.org/rounds/10-studies-highlight-importance-of-rare-disease-research. Accessed 3/15/2022. 
  3. Haendel M, Vasilevsky N, Unni D, et al. How many rare diseases are there? Nat Rev Drug Discov. 2020;19(2):77-78. doi:10.1038/d41573-019-00180-y
  4. Bhatt K. The Importance of Research on Rare Diseases. PLOS SciComm. 3/11/2020. Available at https://scicomm.plos.org/2020/03/11/the-importance-of-research-on-rare-diseases. Accessed 3/15/2022. 
  5. Garrison S, Kennedy A, Manetto N et al. The Economic Burden of Rare Diseases” Quantifying the Sizable Collective Burden and Offering Solutions. Health Affairs. 2/1/2022. Available at https://www.healthaffairs.org/do/10.1377/forefront.20220128.987667. Accessed 3/15/2022. 
  6. National Center for Advancing Translational Sciences. FAQs About Rare Diseases. Genetic and Rare Disease Information Center. Updated 1/26/2021. Available at https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases. Accessed 3/15/2022. 
  7. MedlinePlus. MECP2 gene. Available at https://medlineplus.gov/genetics/gene/mecp2/. Accessed 3/15/2022. 
  8. The Free Medical Dictionary. Rett Syndrome. Available at https://medical-dictionary.thefreedictionary.com/Cerebroatrophic+Hyperammonemia. Accessed 3/15/2022. 
  9. MedlinePlus. PPM-X syndrome. Available at https://medlineplus.gov/genetics/condition/ppm-x-syndrome/. Accessed 3/15/2022. 
  10. MedlinePlus. MECP2-related severe neonatal encephalopathy. Available at https://medlineplus.gov/genetics/condition/mecp2-related-severe-neonatal-encephalopathy/. Accessed 3/15/2022. 
  11. Medline Plus. MECP2 duplication syndrome. Available at https://medlineplus.gov/genetics/condition/mecp2-duplication-syndrome/. Accessed 3/15/2022. 
  12. Kaufmann P, Pariser AR, Austin C. From scientific discovery to treatments for rare diseases – the view from the National Center for Advancing Translational Sciences – Office of Rare Diseases Research. Orphanet J Rare Dis. 2018;13(1):196. Published 2018 Nov 6. doi:10.1186/s13023-018-0936-x
  13. National Center for Advancing Translational Sciences. Therapeutics for Rare and Neglected Diseases. 9/18/2020. Available at https://ncats.nih.gov/trnd. Accessed 3/15/2022. 
  14. National Center for Advancing Translational Sciences. The Accelerating Medicines Partnership Bespoke Gene Therapy Consortium (BGTC). 3/15/2022. Available at https://ncats.nih.gov/programs/BGTC. Accessed 3/15/2022.