Imagine trying to complete a complex jigsaw puzzle when most of the pieces are missing. For decades, that has been the reality of genetic research in Charcot-Marie-Tooth (CMT) disease. Much of what the world knows about CMT has been built from Western patient populations, creating a knowledge base that is valuable but incomplete. If we are serious about developing treatments that work for everyone, the global scientific community must pay far greater attention to the immense and largely untapped genetic diversity of the Indian CMT population.
Today, when a patient undergoes genetic testing for CMT, clinicians compare the results against international databases such as ClinVar and other genomic repositories. These databases help determine whether a genetic variant is disease causing or benign. However, when a variant has never been documented before, it is often classified as a variant of uncertain significance. For patients and families already living with a progressive neurological disorder, this uncertainty can be deeply frustrating. It delays answers, complicates counseling, and can limit access to research opportunities and future therapies.
The problem is particularly relevant in India. A landmark study by Sharma and colleagues examining inherited neuropathies in the Indian population found that a substantial proportion of identified variants were previously unreported in the global literature. This finding highlights a major gap in our collective understanding of CMT genetics. When large populations remain underrepresented in international databases, the consequences extend far beyond national borders. A variant first identified in India may later appear in a patient in New York, Paris, London, or Tokyo. Without adequate representation, clinicians everywhere are working with an incomplete reference library.
The implications go beyond diagnosis. Western cohorts are heavily dominated by CMT1A, which accounts for a large proportion of cases in Europe and North America. In contrast, Indian patients often present with a broader spectrum of disease, including rare autosomal recessive and axonal forms such as CMT2 and CMT4. These subtypes may be less common globally, but they offer valuable insights into the biology of peripheral nerves, myelin maintenance, and axonal degeneration. Studying these conditions is not simply about understanding rare diseases in one country. It is about expanding our understanding of disease mechanisms that affect patients worldwide.
This becomes even more important as CMT research enters a new therapeutic era. Gene therapies, antisense oligonucleotides, RNA-based approaches, and targeted small molecules are moving through preclinical and early clinical development. For the first time, there is genuine optimism that disease-modifying treatments may become a reality. Yet any therapy is only as strong as the evidence supporting it. If future treatments are developed and validated primarily within Western genetic backgrounds, important questions about effectiveness, safety, and generalizability will remain unanswered.
A treatment intended for a global disease should be evaluated using global data.
India represents nearly one sixth of humanity and possesses one of the most genetically diverse populations in the world. Excluding or underrepresenting such a population is not merely an issue of equity. It is a scientific limitation. Greater inclusion of Indian patients in international registries, natural history studies, and clinical trials would strengthen the evidence base for everyone. It would improve variant interpretation, accelerate gene discovery, and help ensure that emerging therapies are relevant across diverse populations.
The conversation therefore needs to shift. Integrating Indian CMT cohorts into global research efforts should not be viewed as an act of inclusion alone. It is a scientific necessity. If the ultimate goal is to develop effective treatments and, one day, a cure for CMT, then the entire puzzle must be assembled. Important pieces of that puzzle are waiting in India.
Priyanshu Agrawal is a physician in India.
