2022 was a breakthrough year for understanding rare diseases. 2023 needs to be better

Major advances in the study and treatment of rare diseases occurred in 2022, from a better understanding of just how many of these diseases exist to the start of new clinical trials that may lead to new therapies.

For the last decade or so, the number of accepted rare diseases has stood between 7,000 and 8,000, though the number had been ticking up. RareX’s Power of Being Counted report, published in June 2022, now puts the number of recognized rare diseases at 10,867, an increase of more than one-third. According to the report, the earlier estimates failed to represent the full spectrum of these diseases.

Overlooking distinctions between diseases can have cascading effects on research, diagnosis, and treatment, so arriving at a more accurate count of the number of rare diseases indicates significant progress in the way patients are categorized and therefore how treatments can be developed.

The increase emerges from a deeper understanding of how rare diseases work and a better picture of every individual’s unique biology. This could be the key to fundamentally changing entire trajectories, from the way rare diseases are evaluated to how therapies are developed and approved, providing hope to the more than 300 million people worldwide living with rare diseases.

Three key advances have driven this seemingly dramatic increase in the number of distinct rare diseases. First, in the past, many people were classified as having a general syndrome, such as autism spectrum disorder. These syndromes are based on symptomatology rather than any specific genetic diagnosis, biologic target, or dysregulated pathway. But as the ability to identify specific genes or pathways implicated in diseases improves, people are moved out of these general classifications and into specific rare disease diagnoses.

Second, many people have undiagnosed rare diseases. Globally, countless individuals are still on their diagnostic journeys, and some of them go undiagnosed for years, or even decades. Some finally get an accurate diagnosis — sometimes with an existing rare disease; sometimes with one that has never before been categorized — while others do not.

Third is that new rare diseases are being discovered all the time. I recently learned of a family in the United States in which two sisters have an ultra-rare condition that no one else in the world has ever been diagnosed with. As the understanding of genetics improves and the cost of genetic evaluation continues to fall, the number of identified rare diseases will keep growing, and perhaps even accelerate.

Treating every person’s disease as unique

The ability to accurately identify and classify rare diseases is crucial, and advances in this area could herald a fundamental change in the way scientists and doctors think about therapies for them. But it is important to realize that individuals with the same outward disease characteristics may have different genetic defects or biologic dysfunctions. Angelman syndrome, for example, has different underlying defects on the same gene that cause similar signs and symptoms, but that does not mean everyone with this syndrome will respond to the same therapies.

A likely outcome of advances in therapeutic development will be that particular therapies will work only for a subset of individuals who have similar genetic defects. On the flip side, it will become much more viable to design therapies that are likely to work for specific subsets of patients.

This also means that what is currently considered one rare disease could potentially become several — which is true for all diseases, not just the rarest ones.

Even if two people have the same disease-causing genetic defect, other genetic differences between them may affect how they metabolize medicine and how their proteins interact with other proteins in the body. The industry is just beginning to build the tools to discover these differences, using computational biology and artificial intelligence to personalize treatments in more targeted ways that treat every disease as rare and specific to the individual.

Innovating toward better outcomes for rare diseases

Drug discovery historically has a 90% failure rate. This has led to a culture of filling pipelines with blockbuster drugs targeted to large populations as a way to offset the cost of failures. This is a key reason why less than 5% of rare diseases have an approved treatment.

But giant leaps in artificial intelligence and machine learning are signaling hope for the millions of people living with rare diseases, helping researchers better develop treatments faster and at lower costs. AI technology is getting better at finding subtle links in large data sets that even the best scientists could miss working manually. Longer training on ever-larger and more robust datasets, along with evolving computational tools, will lead to better way to identify new treatments.

These advances are already yielding results, with the National Institute for Health’s Accelerating Medicines Partnership supporting up to six new clinical trials, each focused on a different rare disease.

For me, one take-away lesson from looking at the trajectory of recent developments in rare diseases is just how young this field is. In the not-too-distant future, the state of diagnostics and therapeutics for them in 2023 will be seen as the stone age. But the rate of improvement makes me optimistic about the future.

Bruce Bloom is the chief collaboration officer at Healx, a company based in Cambridge, England, that uses AI drug discovery to develop new treatments for rare diseases.

First Opinion newsletter: If you enjoy reading opinion and perspective essays, get a roundup of each week’s First Opinions delivered to your inbox every Sunday. Sign up here.