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Updated: Apr 29, 2026
Modeling Charcot-Marie-Tooth Disease In Vitro by Transfecting Mouse Primary Motoneurons
Published on: January 7, 2019
Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal
Lori Sames1, Allison Moore2, Renee Arnold3
1Hannah's Hope Fund, Rexford, NY, 12148, USA.
Abstract:
Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can envision treatment options for these rare diseases in the near future.
Insights
Charcot-Marie-Tooth (CMT) and Giant Axonal Neuropathy (GAN) are rare inherited neuropathies lacking treatments. Further research and patient registries are crucial for developing effective therapies and improving diagnosis for these debilitating conditions.
Area of Science:
- Neurology
- Genetics
- Clinical Research
Background:
- Charcot-Marie-Tooth (CMT) affects approximately 1 in 2500 Americans, characterized by genetic mutations leading to misfolded protein accumulation and progressive nerve damage.
- Giant Axonal Neuropathy (GAN) is an ultra-rare, recessively inherited condition causing progressive nerve death, typically presenting in early childhood and leading to mortality in the second or third decade.
- Both CMT and GAN currently lack approved treatments, highlighting an urgent need for therapeutic development.
Purpose of the Study:
- To identify key areas for advancing research and clinical studies in inherited neuropathies like CMT and GAN.
- To propose novel outcome measures and diagnostic tools for these rare neurological disorders.
- To emphasize the importance of patient registries and collaborative efforts in accelerating therapeutic advancements.
Main Methods:
- Review of current understanding of CMT and GAN disease mechanisms and clinical manifestations.
- Proposal for the integration of electrical impedance myography as a clinical outcome measure for CMT.
- Recommendation for enhanced quality of life assessments and the development of new genetic testing panels for both conditions.
Main Results:
- Current research lacks effective treatments for CMT and GAN, underscoring the need for novel therapeutic strategies.
- Electrical impedance myography and quality of life assessments are proposed as valuable tools for CMT clinical studies.
- Identification of GAN biomarkers and improved genetic testing are essential for accurate diagnosis and patient stratification.
Conclusions:
- Further clinical studies, including the use of electrical impedance myography and comprehensive QoL assessments, are vital for CMT research.
- Developing GAN biomarkers and advanced genetic testing panels are critical steps toward effective management of these inherited neuropathies.
- Leveraging patient registries like the Global Registry of Inherited Neuropathy (GRIN) and engaging patient advocacy groups can significantly accelerate progress in finding treatments for rare inherited neuropathies.
