Darius Ebrahimi-Fakhari
MD, PhD; Director, Movement Disorders Program, Boston Children’s Hospital; Principal Investigator, Spastic Paraplegia Centers of Excellence Research Network (SP-CERN)
Natural history studies help us learn more about rare diseases and how to treat them. Here’s why they are important and how you can get involved.
A natural history study documents the course of a disease over time in the absence of an intervention. Rather than testing a therapy, we observe systematically, applying the same standardised assessments to the same patients across months and years. The objective is to define a disease’s untreated trajectory — its age of onset, rate of progression and the variability between individuals.
Why are these studies important in rare diseases?
The vast majority of rare diseases are genetic in origin, most begin in childhood and are progressive, and for more than 95%1 there is no specific, disease-modifying treatment. Yet robust clinical data remain scarce — patient numbers are small, geographically dispersed and phenotypically heterogeneous. Natural history studies address this directly by characterising how a condition progresses, which clinical features are most informative and how outcomes differ across patients and genotypes.
Such insight is essential for designing adequately powered clinical trials and for determining whether a candidate therapy confers genuine benefit. This is particularly consequential in rare diseases, where small patient populations mean the first clinical trial is often the only opportunity to get it right from the start; a poorly designed study can foreclose a therapeutic avenue for years.
What is it like to participate?
Participation typically involves periodic study visits with standardised clinical evaluations, often complemented by biospecimen collection or wearable sensors between visits. It requires sustained commitment over years. In our experience, however, patients and families find it meaningful — they are contributing directly to the evidence base for their condition and are building a community around a shared cause.
for more than 95%1 there is no specific, disease-modifying treatment
How can people get involved with natural history studies?
The most direct step is to consult a specialist about studies relevant to a given condition. Patient advocacy organisations are also an essential resource. Active studies can be identified on ClinicalTrials.gov, searchable by diagnosis. Each individual who participates strengthens the evidence base on which the entire rare disease community depends.
[1] Elsevier. (2024). The landscape for rare diseases in 2024. https://tinyurl.com/3n79af3b.
