The European CMT community welcomes a definitive new scientific review authored by world-leading experts from the ECRA Board.
In January 2026, the prestigious journal Nature Reviews Disease Primers published a comprehensive guide titled “Charcot-Marie-Tooth disease and related neuropathies.” This publication represents a significant milestone for our community, offering a global consensus on the epidemiology, mechanisms, diagnosis, and management of CMT.
This authoritative review was developed by a distinguished panel of international experts: Joshua Burns, Vincent Timmerman, Matilde Laurá, Eppie M. Yiu, Maurizio D’Antonio, Bipasha Mukherjee-Clavin, Jonathan De Winter, and Steven S. Scherer.
We are particularly proud to highlight that several of these authors are active members of the European CMT Research Association (ECRA) board. Their leadership in this publication underscores ECRA’s pivotal role in driving the global research agenda. Furthermore, the review explicitly acknowledges ECRA for its contributions to the field, cementing the crucial link between patient advocacy organizations and top-tier scientific progress.
1. Global Epidemiology: The Reality of Numbers
For years, the prevalence of CMT was cited as 1 in 2,500. The 2026 review refines this perspective with updated global data.
- Prevalence: The minimum global prevalence is estimated at 17–20 cases per 100,000 individuals.
- Geographic Variation: The distribution is not uniform. High prevalence rates are observed in countries like Norway (38.8/100,000) and Egypt (80/100,000), often due to founder effects and robust registry systems. In contrast, other regions like South Korea report lower rates (5.2/100,000).
- The Diagnostic Gap: The authors emphasize that CMT remains significantly underdiagnosed worldwide. Limitations in accessing genetic testing and the subtle presentation of milder phenotypes mean that the actual number of people living with CMT is likely higher than current registries suggest.
2. The Genetic Landscape and Diagnosis
CMT is a highly heterogeneous group of disorders caused by mutations in over 130 distinct genes. These mutations disrupt the peripheral nerves by damaging either the myelin sheath (demyelinating forms, e.g., CMT1) or the axon (axonal forms, e.g., CMT2).
The Modern Diagnostic Pathway The review outlines an updated diagnostic algorithm that moves beyond traditional methods:
- Clinical Assessment: Remains the foundation, identifying classic signs such as distal muscle weakness, foot deformities (pes cavus), and sensory loss.
- Advanced Sequencing: While testing for the PMP22 duplication (CMT1A) remains the first step, the standard of care for undiagnosed cases is shifting toward Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS).
- New Technologies: A key development highlighted in 2026 is the use of Long-read Sequencing. This technology is crucial for detecting complex structural variants and mutations in difficult-to-sequence genes (such as SORD or RFC1) that standard panels may miss.
3. Standards of Care: Optimizing Quality of Life
While the search for a cure continues, the review reinforces the importance of multidisciplinary management to mitigate disability.
- Rehabilitation: Targeted exercise (aerobic and resistance training) is safe and effective for maintaining muscle function and cardiorespiratory health.
- Orthotic Management: The use of Ankle-Foot Orthoses (AFOs) is strongly recommended to manage foot drop, improve gait efficiency, and reduce fall risk.
- Surgical Intervention: Orthopaedic surgery for foot deformities and scoliosis remains a vital option but requires assessment by specialized surgical teams experienced in neuromuscular conditions.
4. The Future is Now: Therapeutic Pipeline
Perhaps the most encouraging section of the review details the transition from symptomatic management to disease-modifying therapies. Several candidates have moved from the laboratory to clinical trials:
- Silencing PMP22 (for CMT1A): Strategies to lower the toxic overexpression of the PMP22 gene are in advanced stages. These include EDK060 (a siRNA therapy currently in Phase 1) and other antisense oligonucleotide (ASO) approaches.
- Metabolic Targets (for CMT-SORD & HSN1):
- AT-007 (Govorestat): A breakthrough inhibitor for CMT-SORD that prevents the accumulation of toxic sorbitol, currently in advanced trials.
- L-Serine: Oral supplementation is being trialed (NCT06113055) to reduce neurotoxic sphingolipids in HSN1.
- Cellular Stress and Axonal Transport: Agents like IFB-088 (Sephin1) are being tested to help Schwann cells manage protein stress, while HDAC6 inhibitors aim to restore defective axonal transport in CMT2.
- Gene Therapy: For rare, severe forms such as CMT2S (caused by IGHMBP2), viral-vector gene replacement therapies (AAV9) represent a cutting-edge frontier.
Conclusion
This publication in Nature Reviews serves as a global reference point for the next decade. It validates the complexity of CMT, the necessity of specialized care, and the tangible hope offered by emerging therapies.
The European CMT Federation applauds the authors and ECRA for this monumental work. It is a testament to what can be achieved when clinical excellence and patient-centric research organizations collaborate.
Reference: Burns, J., Timmerman, V., Laurá, M., et al. (2026). Charcot-Marie-Tooth disease and related neuropathies. Nature Reviews Disease Primers.
