Improving Prospects for Rare Diseases
A rare disease is typically defined as one affecting fewer than 1 in 2,000 people in Europe or 1 in 1,500 people in the United States. Howevere, with more than 7,000–10,000 identified rare conditions (and many more unidientified), rare diseases together affect an estimated 300 million people worldwide.
Most rare diseases are severe, lifelong, and they are overwhelmingly genetic in orgin. Many appear in childhood, often without warning. Yet despite the scale of impact, fewer than 5–10% of rare diseases currently have an approved treatment. For most patients, care focuses on managing symptoms rather than targeting underlying causes.
A Long Road to Diagnosis
A major challenge for families is the “diagnostic odyssey.” Many patients spend 5–8 years seeking answers, consulting multiple specialists, and often receiving misdiagnoses. Even with modern genetic testing, more than half of those with a rare disease go undiagnosed globally. Without a clear diagnosis, access to specialist care, support groups, and clinical trials becomes extremely difficult.
Newborn genome sequencing, improved data-sharing, and AI-assisted interpretation are helping shorten this journey. But the gap remains large, and many people still live with unexplained symptoms for years.
How Whole Genome Sequencing and Gene Therapy Is Changing the Landscape
Whole genome sequencing (WGS) is rapidly reshaping how rare diseases are diagnosed. By reading all 3 billion letters of an individual’s DNA rather than focusing on a limited set of genes, WGS dramatically increases the chances of finding the root genetic cause of a condition. For families stuck in the diagnostic odyssey, WGS can reduce years of uncertainty to just days or weeks, especially in newborns with unexplained symptoms. It also uncovers previously unknown variants, helping researchers identify entirely new rare diseases. As WGS becomes faster and more affordable, it is moving from specialist research centres into routine clinical care—bringing earlier, more accurate diagnoses to thousands who previously had no answers.
In the last decade, gene therapy has shifted rare-disease medicine from symptom management toward addressing root causes. Using viral vectors or genome-editing tools like CRISPR, scientists can add functional genes, silence harmful ones, or even rewrite DNA.
A handful of landmark gene therapies illustrate this potential:
- Luxturna, restoring functional vision in people with inherited retinal disorders caused by RPE65 mutations.
- Zolgensma and other SMA gene therapies, transforming outcomes for infants with spinal muscular atrophy.
- Casgevy (CRISPR-based) and Lyfgenia for sickle cell disease, representing the first wave of genome-editing treatments approved for patients.
These advances show what is possible for monogenic disorders—yet they currently benefit only a small fraction of rare diseases, and they come with barriers: high costs, complex delivery, and limited long-term data.
The Emerging Role of Exosome Research
While gene therapy grabs headlines, exosome research is quietly building another pathway that could help thousands of rare-disease patients. The unique properties of exosomes make them promising tools for rare-disease treatment:
- Natural Delivery Vehicles
Unlike viral vectors used in gene therapy, exosomes are non-immunogenic, meaning the body generally does not see them as foreign. This makes them attractive for delivering RNA therapies, gene-editing tools and therapeutic proteins.
For rare diseases where immune reactions to traditional gene therapies pose risks, exosome-based delivery may offer a safer alternative.
- Ability to Cross the Blood–Brain Barrier
This is especially powerful for neurological rare diseases, such as Batten disease, Krabbe disease and Metachromatic leukodystrophy.
Most treatments struggle to reach the brain. Exosomes, however, can cross biological barriers and deliver therapies directly to affected neurons.
- Personalised Medicine Potential
Because exosomes can be derived from a patient’s own cells, they may reduce rejection risks and enable customised treatment approaches. For ultra-rare diseases with only a handful of patients, patient-specific exosome therapeutics could fill a major gap.
- Biomarkers for Earlier Diagnosis
Exosomes carry disease-specific molecular signatures. This makes them promising diagnostic tools, especially for conditions where early detection is essential to prevent irreversible damage. In disorders such as muscular dystrophies or rare metabolic diseases, exosome biomarkers could enable earlier intervention and better outcomes.
Though still emerging, exosome-based therapies are moving rapidly toward clinical trials. Within the next decade, they may complement or even rival gene therapy in treating rare diseases.
Clinical Trials are Challenging with so Few Patients
Rare diseases pose unique challenges to clinical research:
- Small patient populations make traditional large trials impossible.
- Patients are often geographically dispersed.
- Biological variability makes outcome measures harder to standardise.
To overcome this, researchers and regulators are adopting more flexible approaches:
- Adaptive trial designs that adjust dosing or endpoints as data emerges.
- Natural history studies, comparing treated patients to detailed disease-progression data.
- Platform trials, where several therapies are evaluated under one umbrella protocol.
- Decentralised trials, using home monitoring and telemedicine to reduce travel burdens.
Regulatory agencies now accept alternative evidence paths, such as strong biomarker data or single-arm studies, when randomised controlled trials are not feasible.
For the millions living with rare conditions, prospects are improving: faster diagnoses, more equitable access to therapies, and innovative treatment strategies that finally match the scale and urgency of their needs.
IMAGE Barth Disease CREDIT Clark et al
Learn more about powerful technologies that are enabling research:
