As it did during the COVID-19 pandemic, mRNA technology offers an efficient way forward in developing products for diseases that lack approved treatments.
Despite the small numbers of people affected by individual rare diseases overall, one out of every 10 Americans will be diagnosed with a rare disease, and an incredible 300 million people globally are living with a disease classified as rare. Rare Disease Day on February 28 is an opportunity to spotlight the hurdles people with rare diseases face and the scientific advances that could offer hope for the countless families across the globe affected by this composite of disparate conditions.
One of those advances is mRNA technology, which rocketed to fame several years ago thanks to the vaccines developed in record time during the pandemic. As head of development for therapeutics and oncology at Moderna, a company rooted in the promise of mRNA, I believe this technology’s potential uses go far beyond vaccines, and that one of the areas where we could see them make a big difference is in rare diseases where multiple barriers have so far prevented the development of effective therapies.
Obstacles to Advancing Rare Disease Research
Life with a rare disease is typically defined by more questions than answers. On average, it takes four to five years for a person with a rare disease to receive the correct diagnosis, but in some cases, it can take over a decade. Because there are over 7,000 rare diseases identified, it is nearly impossible for healthcare providers to be intimately familiar with all of them and their symptom presentation. Even after diagnosis, many people discover that no effective treatment exists for their condition—more than 90% of rare diseases have no approved therapies. Without appropriate treatment, patients and their families often need to manage these severe conditions with supportive care such as following a strict diet.
The very nature of rare disease brings a unique set of challenges when conducting research, which is critical to advancing our understanding of the etiology, mechanisms and epidemiology of these diseases. Both private and public funding for rare disease preclinical work tends to be limited due to the relatively small market size. Further, once a candidate is developed, it can be difficult to enroll enough participants in a clinical trial to gather statistically significant data. This, coupled with the heterogeneity of presentation within a single disease and factoring in off-label drugs or other treatments patients may be undergoing, means trial design and data interpretation can be complex. While the FDA and EMA have introduced frameworks to account for these limitations and expedite approvals for rare disease therapies, there is still a balancing act when it comes to safety and efficacy when working with limited data.
A Hopeful Path Forward
Many rare diseases are caused by intracellular protein and enzyme deficiencies. However, current treatment approaches don’t allow for correct localization of these proteins inside the cell unless they are made naturally by the cell.
The use of mRNA to instruct the cell to make these proteins can overcome this challenge. Long before mRNA became widely known during the COVID-19 pandemic, the technology was investigated as a therapeutic. With mRNA therapeutics, we can instruct cells to produce a functional version of the specific protein that is missing or defective. The flexibility and adaptability of mRNA technology means it could potentially solve a wide range of protein deficiencies. For example, propionic acidemia (PA) and methylmalonic acidemia (MMA) are inherited errors of metabolism that disrupt the way the body breaks down food. They are often caused by missing or not completely functional proteins that normally help turn food into energy, which can lead to developmental delays and damage to the brain and other organs. Investigational mRNA therapies are being evaluated in clinical trials by Moderna to treat these rare metabolic disorders.
Among the many people affected by rare diseases whom I’ve had the pleasure of working with, there is a common theme: the solace they find in knowing they’re not alone. As someone whose career involves investigating treatments for rare disease, the advancements being made every day in understanding the science behind these diseases and the therapies that could target them are more promising than ever before. We must continue to shed light on the experience of people with rare diseases, identify the hurdles that can prolong their burden, and create solutions that offer hope.
