New Developments in CMT Research from the 2026 PNS Annual Meeting
From 13 to 16 June 2026, Maastricht hosted the Annual Meeting of the Peripheral Nerve Society – PNS, one of the leading international events dedicated to peripheral neuropathies.
The European CMT Federation – ECMTF gathered the main developments presented during the meeting in the article From Genes to Daily Life: CMT Research Highlights from the 2026 PNS Annual Meeting in Maastricht,written by Filippo Genovese and published on 30 June 2026.
The overall picture is one of a rapidly evolving field of research—not because of a single decisive discovery, but thanks to interconnected progress in genetic diagnosis, understanding disease mechanisms, developing new therapies, identifying biomarkers and improving the quality of life of people living with CMT.
Genetic diagnosis is becoming increasingly important
One of the main messages emerging from the meeting concerned the importance of genetic diagnosis.
Precisely identifying the gene responsible does not simply mean giving the disease a specific name. It can provide useful information for clinical care, family counselling, participation in research projects and, in the future, access to trials targeting a specific CMT subtype.
The studies presented in Maastricht confirmed the considerable genetic heterogeneity of Charcot-Marie-Tooth disease. The genes most commonly involved may vary across different geographical areas and, alongside the best-known forms, rare variants and new genes associated with inherited neuropathies continue to be identified.
Technologies such as long-read sequencing, RNA sequencing, pangenome analysis and certain artificial intelligence-based tools may help solve cases that have remained undiagnosed after conventional genetic testing. For some people, it may therefore be useful in the future to reassess genetic results obtained several years ago.
Understanding the different mechanisms of CMT
CMT is not a single disease, but a large family of inherited neuropathies. The different forms may be caused by very different mechanisms.
In some cases, an excessive amount of a protein is produced; in others, the protein is insufficient, altered or toxic. Myelin, axonal transport, mitochondrial function, energy production and cellular stress responses may also be involved.
To study these processes, researchers are using models that increasingly resemble the human disease: patient-derived stem cells, motor neurons, sensory neurons, Schwann cells, organoids and complex cellular systems.
These tools make it possible to observe in the laboratory what happens in the different forms of CMT and to assess potential therapeutic strategies before moving on to clinical trials.
Gene therapies: different strategies for different forms
Professor Kleopas Kleopa presented an overview of the current state of gene therapies for CMT neuropathies.
The strategies being studied include replacing a missing gene, reducing the activity of an overexpressed gene, silencing a harmful copy, correcting DNA and compensating for an impaired cellular process.
One of the main challenges is delivering the treatment to the affected cells. In axonal forms, such as CMT2, the target may be motor neurons, sensory neurons or the long axons themselves. In demyelinating forms, however, treatment must mainly reach Schwann cells.
For this purpose, researchers are studying viral vectors, including AAV-based systems, as well as non-viral approaches such as nanoparticles and different routes of administration.
CMT2A: restoring mitochondrial balance
In the section dedicated to CMT2A, Filippo Genovese writes:
“In CMT2A, caused by MFN2 mutations, researchers are exploring ways to restore mitochondrial balance by replacing, increasing or correcting mitofusin function.”
— Filippo Genovese, European CMT Federation – ECMTF
This is a particularly significant indication for our community. The strategies described aim to intervene in the mechanisms directly connected to the MFN2 gene and mitofusin function.
Most of these projects are still at the laboratory or animal-testing stage. The message emerging from the meeting is therefore one of cautious optimism: research is moving towards treatments designed around the specific genetic cause of the disease, but further studies are still required to assess their effectiveness and safety in people.
Experimental drugs and muscle activation
Alongside therapies targeting the genetic cause, researchers are also studying treatments designed to improve nerve function, muscle activation, myelin repair or cellular stress responses.
Preliminary results from the SYNAPSE-CMT study of ignaseclant, previously known as NMD670, were also presented during the meeting.
This is an experimental oral drug designed to improve skeletal muscle activation. The study involved 81 adults with a genetically confirmed diagnosis of CMT1 or CMT2.
The six-minute walk test, selected as the primary endpoint, did not show a treatment effect. However, encouraging signals were observed in some secondary assessments, including grip strength, hand dexterity and certain lower-limb functional measures.
These findings remain preliminary and will need to be confirmed through larger and longer-term studies.
Measuring disease progression more accurately
To determine whether a treatment works, researchers need tools capable of measuring changes caused by the disease with precision.
This can be particularly challenging in CMT because progression is often slow and varies according to age, severity and genetic subtype.
Several studies therefore focused on clinical assessment scales used in adults and children, the training of professionals who carry out these tests and the development of digital tools.
Wearable sensors and movement analysis using smartphone-recorded videos could, in the future, make it possible to assess walking and balance in everyday life, rather than only during hospital visits.
Biomarker research
Another central theme was the study of biomarkers—measurable indicators that may help track disease progression or determine whether a treatment is having an effect.
The tools being investigated include blood neurofilament light chain, certain plasma proteins, RNA-based markers, urine tests, muscle magnetic resonance imaging, nerve ultrasound, magnetic resonance neurography and skin biopsy.
No biomarker suitable for every form of CMT has yet been identified. Research is therefore focused on finding indicators that are sufficiently sensitive, specific to individual subtypes and easy to use in clinical trials.
In the future, these tools may make it possible to detect the effect of a treatment before clear clinical changes become visible.
Rehabilitation, orthoses and everyday life
Not all the research presented in Maastricht concerned future therapies. Many studies addressed issues that already affect the daily lives of people with CMT, including walking difficulties, balance, falls, fatigue, pain, sleep disorders, physical activity and the use of orthoses.
In children and adolescents, the use of customised foot orthoses was associated with improvements in walking speed and step length, together with a reduction in episodes of ankle instability, tripping and falling.
Balance rehabilitation programmes developed with the direct involvement of people with CMT were also presented. Participants highlighted the need for programmes that are flexible, safe and adaptable to different abilities and to daily variations in symptoms.
Studies on fatigue and sleep also remind us that care should not focus solely on weakness in the hands and feet. Pain, psychological well-being, school, employment and social participation must also be taken into account.
People with CMT as research partners
The meeting also included a session in which four people living with peripheral neuropathy brought the patient perspective directly into the scientific programme.
People living with the disease can help researchers identify the issues that have the greatest impact on everyday life: delayed diagnosis, fatigue, pain, falls, the use of orthoses, access to physiotherapy, employment, education, family planning and the emotional impact of disease progression.
According to the European CMT Federation, people with CMT should not be consulted only after decisions have already been made. They should contribute from the outset to defining research priorities and the tools used in studies.
From research to everyday life
The 2026 PNS Annual Meeting showed a rapidly evolving scientific field.
Genetic diagnosis is becoming increasingly precise, experimental models are improving our understanding of the different mechanisms underlying CMT and therapeutic strategies are being developed for numerous subtypes.
At the same time, research into rehabilitation, orthoses, balance, fatigue and sleep disorders can already help improve quality of life.
For CMT2A, strategies aimed at restoring mitochondrial balance by acting on mitofusin function represent an important direction of research. This work remains experimental and requires scientific rigour and caution in communication, but it confirms the growing attention being devoted to the specific mechanisms associated with MFN2.
Source: European CMT Federation – ECMTF
Author of the original article: Filippo Genovese
Original title: From Genes to Daily Life: CMT Research Highlights from the 2026 PNS Annual Meeting in Maastricht
Published: 30 June 2026
Italian summary and adaptation by Progetto Mitofusina 2 ETS
From 13 to 16 June 2026, Maastricht hosted the Annual Meeting of the Peripheral Nerve Society – PNS, one of the leading international events dedicated to peripheral neuropathies.
The European CMT Federation – ECMTF gathered the main developments presented during the meeting in the article From Genes to Daily Life: CMT Research Highlights from the 2026 PNS Annual Meeting in Maastricht,written by Filippo Genovese and published on 30 June 2026.
The overall picture is one of a rapidly evolving field of research—not because of a single decisive discovery, but thanks to interconnected progress in genetic diagnosis, understanding disease mechanisms, developing new therapies, identifying biomarkers and improving the quality of life of people living with CMT.
Genetic diagnosis is becoming increasingly important
One of the main messages emerging from the meeting concerned the importance of genetic diagnosis.
Precisely identifying the gene responsible does not simply mean giving the disease a specific name. It can provide useful information for clinical care, family counselling, participation in research projects and, in the future, access to trials targeting a specific CMT subtype.
The studies presented in Maastricht confirmed the considerable genetic heterogeneity of Charcot-Marie-Tooth disease. The genes most commonly involved may vary across different geographical areas and, alongside the best-known forms, rare variants and new genes associated with inherited neuropathies continue to be identified.
Technologies such as long-read sequencing, RNA sequencing, pangenome analysis and certain artificial intelligence-based tools may help solve cases that have remained undiagnosed after conventional genetic testing. For some people, it may therefore be useful in the future to reassess genetic results obtained several years ago.
Understanding the different mechanisms of CMT
CMT is not a single disease, but a large family of inherited neuropathies. The different forms may be caused by very different mechanisms.
In some cases, an excessive amount of a protein is produced; in others, the protein is insufficient, altered or toxic. Myelin, axonal transport, mitochondrial function, energy production and cellular stress responses may also be involved.
To study these processes, researchers are using models that increasingly resemble the human disease: patient-derived stem cells, motor neurons, sensory neurons, Schwann cells, organoids and complex cellular systems.
These tools make it possible to observe in the laboratory what happens in the different forms of CMT and to assess potential therapeutic strategies before moving on to clinical trials.
Gene therapies: different strategies for different forms
Professor Kleopas Kleopa presented an overview of the current state of gene therapies for CMT neuropathies.
The strategies being studied include replacing a missing gene, reducing the activity of an overexpressed gene, silencing a harmful copy, correcting DNA and compensating for an impaired cellular process.
One of the main challenges is delivering the treatment to the affected cells. In axonal forms, such as CMT2, the target may be motor neurons, sensory neurons or the long axons themselves. In demyelinating forms, however, treatment must mainly reach Schwann cells.
For this purpose, researchers are studying viral vectors, including AAV-based systems, as well as non-viral approaches such as nanoparticles and different routes of administration.
CMT2A: restoring mitochondrial balance
In the section dedicated to CMT2A, Filippo Genovese writes:
“In CMT2A, caused by MFN2 mutations, researchers are exploring ways to restore mitochondrial balance by replacing, increasing or correcting mitofusin function.”
— Filippo Genovese, European CMT Federation – ECMTF
This is a particularly significant indication for our community. The strategies described aim to intervene in the mechanisms directly connected to the MFN2 gene and mitofusin function.
Most of these projects are still at the laboratory or animal-testing stage. The message emerging from the meeting is therefore one of cautious optimism: research is moving towards treatments designed around the specific genetic cause of the disease, but further studies are still required to assess their effectiveness and safety in people.
Experimental drugs and muscle activation
Alongside therapies targeting the genetic cause, researchers are also studying treatments designed to improve nerve function, muscle activation, myelin repair or cellular stress responses.
Preliminary results from the SYNAPSE-CMT study of ignaseclant, previously known as NMD670, were also presented during the meeting.
This is an experimental oral drug designed to improve skeletal muscle activation. The study involved 81 adults with a genetically confirmed diagnosis of CMT1 or CMT2.
The six-minute walk test, selected as the primary endpoint, did not show a treatment effect. However, encouraging signals were observed in some secondary assessments, including grip strength, hand dexterity and certain lower-limb functional measures.
These findings remain preliminary and will need to be confirmed through larger and longer-term studies.
Measuring disease progression more accurately
To determine whether a treatment works, researchers need tools capable of measuring changes caused by the disease with precision.
This can be particularly challenging in CMT because progression is often slow and varies according to age, severity and genetic subtype.
Several studies therefore focused on clinical assessment scales used in adults and children, the training of professionals who carry out these tests and the development of digital tools.
Wearable sensors and movement analysis using smartphone-recorded videos could, in the future, make it possible to assess walking and balance in everyday life, rather than only during hospital visits.
Biomarker research
Another central theme was the study of biomarkers—measurable indicators that may help track disease progression or determine whether a treatment is having an effect.
The tools being investigated include blood neurofilament light chain, certain plasma proteins, RNA-based markers, urine tests, muscle magnetic resonance imaging, nerve ultrasound, magnetic resonance neurography and skin biopsy.
No biomarker suitable for every form of CMT has yet been identified. Research is therefore focused on finding indicators that are sufficiently sensitive, specific to individual subtypes and easy to use in clinical trials.
In the future, these tools may make it possible to detect the effect of a treatment before clear clinical changes become visible.
Rehabilitation, orthoses and everyday life
Not all the research presented in Maastricht concerned future therapies. Many studies addressed issues that already affect the daily lives of people with CMT, including walking difficulties, balance, falls, fatigue, pain, sleep disorders, physical activity and the use of orthoses.
In children and adolescents, the use of customised foot orthoses was associated with improvements in walking speed and step length, together with a reduction in episodes of ankle instability, tripping and falling.
Balance rehabilitation programmes developed with the direct involvement of people with CMT were also presented. Participants highlighted the need for programmes that are flexible, safe and adaptable to different abilities and to daily variations in symptoms.
Studies on fatigue and sleep also remind us that care should not focus solely on weakness in the hands and feet. Pain, psychological well-being, school, employment and social participation must also be taken into account.
People with CMT as research partners
The meeting also included a session in which four people living with peripheral neuropathy brought the patient perspective directly into the scientific programme.
People living with the disease can help researchers identify the issues that have the greatest impact on everyday life: delayed diagnosis, fatigue, pain, falls, the use of orthoses, access to physiotherapy, employment, education, family planning and the emotional impact of disease progression.
According to the European CMT Federation, people with CMT should not be consulted only after decisions have already been made. They should contribute from the outset to defining research priorities and the tools used in studies.
From research to everyday life
The 2026 PNS Annual Meeting showed a rapidly evolving scientific field.
Genetic diagnosis is becoming increasingly precise, experimental models are improving our understanding of the different mechanisms underlying CMT and therapeutic strategies are being developed for numerous subtypes.
At the same time, research into rehabilitation, orthoses, balance, fatigue and sleep disorders can already help improve quality of life.
For CMT2A, strategies aimed at restoring mitochondrial balance by acting on mitofusin function represent an important direction of research. This work remains experimental and requires scientific rigour and caution in communication, but it confirms the growing attention being devoted to the specific mechanisms associated with MFN2.
Source: European CMT Federation – ECMTF
Author of the original article: Filippo Genovese
Original title: From Genes to Daily Life: CMT Research Highlights from the 2026 PNS Annual Meeting in Maastricht
Published: 30 June 2026
Italian summary and adaptation by Progetto Mitofusina 2 ETS
