The rare disease revolution: how it will help shape the future of medicine

In an article by University of Dundee student Ferenc Gutai, we examine the current state of rare disease research and explore how it will drive the next step of medical innovation, touching on scientific areas such as genetics and biomarkers, as well as diving into exciting developments that have resulted in ever closer involvement of patients in drug development and clinical trial design.

Rare disease research will drive the next steps of medical innovation- not only in terms of rare diseases, but also for afflictions which are similar but more commonly found in patients. Through the usage of Next-generation sequencing (NGS) and biomarkers, as well as the patients’ own experiences and voices, we will be able to progress in our treatment of these difficult diseases and related maladies.

Next-generation sequencing

NGS reduces genomic sequencing time for virtually the same cost as previous methods, and represents diagnostic testing’s future.

Rare diseases are often misdiagnosed or detected too late for meaningful therapies to be administered. The UK’s Deciphering Developmental Disorders study demonstrated the diagnostic power of NGS in detecting novel genes associated with developmental disorders that would have been overlooked by traditional models. The evidence has spurred curating of genetic registries which will benefit scientists by allowing for shared allocation of resources and an increased sample population.

Ongoing research into cheaper, sustainable workflow models of large scale genomic studies will close the gap between laboratory and clinical genetics.

Rare diseases

Rare diseases are crucial towards improving our understanding of the pathophysiology behind similar disorders.

One example is the ongoing research into Fibrodysplasia Ossificans Progressiva. In this fatal connective tissue disorder, patients experience gradual loss of movement as muscles turn into bone, a process known as heterotopic ossification, with the usual cause of death being thoracic insufficiency syndrome.

Rare diseases are crucial towards improving our understanding of the pathophysiology behind similar disorders.

Heterotopic ossification is prevalent in many types of musculoskeletal injuries and cardiovascular disease processes as well as aspects of regenerative medicine. One cell that was theorized to have a key function in this process is the osteoclast, which is responsible for bone resorption. As such, bisphosphonates were proposed as therapy to suppress osteoclast function. The attention to this disease has highlighted the lack of importance that osteoclasts hold in heterotopic ossification, shedding further light on this process and allowing for treatment adjustments.

The shared signaling pathway defects between rare and common diseases mean that elucidating the pathophysiology behind one disease will shed light on a whole range of clinically different, but biochemically similar disorders.


Rare disorders have encouraged employment of better methods for detecting and classifying them, beyond traditional examinations – this has shifted the focus of diagnosis to biomarkers, so called characteristics that indicate normal or pathogenic processes. By providing clinicians with a measurable feature of a disease, we can achieve earlier diagnoses, improved assessment of disease severity, and more personalized treatments.

Biomarkers have positively impacted drug trials by allowing researchers to select patients who fit the disease category in question and will not react adversely to medication, allowing for safer, more relevant data to be collected. Although the paucity of patient data has been recognized as a limitation to identifying potential biomarkers, establishing global databases will help this problem.

Clinical innovation

Rare diseases can pave the way with regards to how treatment is designed with all of the stakeholders in mind. The majority of the patient’s medical journey lies in the therapy phase. There is a wealth of untapped potential amongst the patient-carer population for unique and innovative solutions towards dealing with their disease.

For example, the Personalized External Aortic Root Support was designed by an engineer diagnosed with aortic dilation as a complication of a rare connective tissue disorder called Marfan’s syndrome. The diverse experiences and concerns of the patient population suggest much more opportunity for creative solutions, provided that there are appropriate communication systems in place to help bring these ideas into practice.

Patient voices

Patient Advocacy Groups (PAGs) are the next aspect which will help increase patient participation in the care model.

Encouragingly, journals are also showing a shift towards publishing articles that have been co-produced by patients and researchers (such as the patient involvement journal, Research Involvement and Engagement.

PAGs can help facilitate patient recruitment, spread awareness of studies, and develop funding for research. Pharmaceutical companies have also recognized the significant value of patient involvement in the drug development process, one of the driving forces behind the creation of the European Patient’s Academy, an initiative to improve patient contribution in drug research.

By establishing platforms for patients to voice their opinions and concerns, we can raise the bar for treatment standards of all diseases, allowing for better alignment between the objectives of the medical and patient communities.

Rare disease patients can help scientists, pharmaceutical companies, and clinicians better understand the effect of therapy on patient Quality of Life (QoL). Patient-reported outcomes have become more recognized as a cost-effective assessor for the public impact of drugs before they are publicly released. Furthermore, the nature of rare diseases has encouraged the creation of outcome measures that pertain to QoL and functional status, rather than disease specific measures.

Encouragingly, journals are also showing a shift towards publishing articles that have been co-produced by patients and researchers (such as the patient involvement journal, Research Involvement and Engagement, which in itself is co-produced), signifying that we may be entering an epoch of patient-centered medical research.

Final thoughts

It is clear that the challenges and setbacks that come with researching rare diseases have forced innovation among the scientific community. Researchers, pharmaceutical companies, clinicians, and patients from all around the world are rallying together to tackle this issue.

View the latest posts on the On Medicine homepage