With active research projects totaling $4.41 million in investment, CMTA is the only organization supporting a coordinated CMT1A research ecosystem spanning disease models, drug development, delivery science, natural history and biomarkers, and clinical infrastructure,.
The CMTA-STAR Ecosystem | A Coordinated Approach to CMT1A
CMT1A is the most common type of Charcot-Marie-Tooth disease (CMT), accounting for approximately two-thirds of genetically diagnosed cases. Moving a therapy from idea to clinical trial requires more than a promising candidate. Researchers must be able to model disease biology, evaluate therapeutic approaches, deliver treatments to peripheral nerves, measure biological and clinical responses, and conduct trials in well-characterized patient populations. CMTA-STAR research investments have created a powerful ecosystem to span these areas, connecting the scientific, translational, and clinical resources required to bring new therapies into clinical testing. This research is showing tangible progress toward new treatments for this common genetic subtype of CMT.
Disease Models
Drug development requires human-relevant models to test candidate therapies before they reach patients. CMTA supports projects that are expanding the range of human-relevant models available for CMT1A research.
At the University of Antwerp, the lab of Vincent Timmerman, PhD, is developing three-dimensional neuromuscular organoids, lab-grown tissue structures that replicate the cellular architecture of peripheral nerve and muscle, incorporating Schwann cells generated from CMT1A patient-derived iPSC lines. This could make drug testing faster, cheaper and more accurately reflect the effects on humans.
At Hasselt University in Belgium, a completed project in the lab of Esther Wolfs, PhD, generated patient-derived Schwann cell lines from dental pulp stem cells representing eight CMT subtypes, creating a scalable human cell platform for early-stage drug screening. Although this project has been completed, CMTA continues to support this work through an active Patients as Partners in Research Opportunity. The Wolfs team are highly collaborative and have supplied these cells to several projects that are also advancing CMT research and treatment development.
CMTA also partnered with Anatomic to develop a new CMT1A patient-derived Schwann Cell precursor assay. Using cutting edge technologies, the assay can detect if candidate treatments are able to reduce PMP22 levels. The assay is now available through CMTA’s Preclinical Toolbox along with best-in-class mouse and rat models of CMT1A. These models are available to our global network of research partners and lower the barriers to the development of treatments for CMT. Together, these platforms provide researchers with human-derived and animal systems for studying CMT1A disease biology and evaluating candidate therapies before clinical testing. The impact of these tools is magnified as they are shared across the research landscape.
Drug Development
Three active CMTA-funded projects are pursuing distinct therapeutic mechanisms for CMT1A, each targeting PMP22 overexpression through a different biological route.
A collaboration between the labs of Bruce Conklin, MD, John Svaren, PhD, and Maurizio D’Antonio, PhD, is applying CRISPR-Cas9 gene editing to CMT1A and CMT1B by targeting PMP22 and MPZ. Key regulatory elements for allele-specific editing have been identified, and guide RNA design is underway.
The lab of Jordan VerPlank, PhD, at the Uniformed Services University of the Health Sciences (USUHS), is evaluating cGMP pathway activation as a mechanism to increase PMP22 degradation in Schwann cells. Three medicines that increase cGMP through different mechanisms are currently being evaluated in CMT1A mouse models.
At Albany Medical College, the labs of Sophie Belin, PhD, and Yannick Poitelon, PhD, are testing a lead compound targeting a regulator of PMP22 expression in Schwann cells. The compound has demonstrated dose-dependent PMP22 reduction in preclinical studies.
These programs reflect the diversity of therapeutic approaches being explored for CMT1A, from gene editing and transcriptional regulation to modulation of protein homeostasis. This diversity of approach increases the likelihood that effective therapies can be identified and advanced into clinical development.
Delivery Science
Effective therapies require viable delivery to where they need to go: the peripheral nerves. The blood-nerve barrier limits access to Schwann cells and neurons. A key CMTA-STAR research priority is to address this challenge, and four delivery projects are in progress to evaluate different non-viral approaches.
At Yale University, the lab of Jiangbing Zhou, PhD, is evaluating a non-viral delivery system for genome-editing cargo, including CRISPR-based constructs. The project is testing whether genome-editing therapies can be delivered to Schwann cells and peripheral neurons across multiple routes of administration.
At the Icahn School of Medicine at Mount Sinai, the lab of Yizhou Dong, PhD, is developing blood-nerve barrier-crossing conjugates designed to transport RNA-based therapies into Schwann cells and peripheral neurons.
At the National Research Council Canada, the lab of Umar Iqbal, PhD, is developing Schwann cell-targeted peptide-lipid nanoparticles for delivery of siRNA targeting PMP22 in CMT1A. This approach combines cell-specific targeting with the established manufacturing and safety advantages of lipid nanoparticle platforms.
At the Cyprus Institute of Neurology and Genetics, co-funded with the Muscular Dystrophy Association, the lab of Alexia Kagiava, PhD, is evaluating nanoparticle-based gene delivery . Recent studies confirmed successful delivery of genetic cargo to peripheral nerve cells, supporting further development of this platform for Schwann cell-involved subtypes of CMT.
Because delivery remains a shared challenge across treatment development, advances in these platforms could benefit multiple therapeutic programs simultaneously.
Natural History and Biomarkers
Clinical trials require validated outcome measures and biomarkers to demonstrate that a therapy is working. CMTA supports active projects that are developing these essential tools in CMT1A.
The ACT-CMT Extension Study, led by David Herrmann, MBBCh, at the University of Rochester and conducted across four CMTA Centers of Excellence, is generating longitudinal natural history data and initiating plasma PMP22 measurements as a candidate disease biomarker.
At the University of Michigan, the lab of Gabriel Corfas, PhD, is evaluating hearing and balance assessments as candidate outcome measures for CMT1A clinical trials.
Without reliable biomarkers and outcome measures, potential therapies can be difficult to evaluate in clinical trials. These projects are helping build the tools needed to measure treatment effects and support future trial readiness.
Clinical Infrastructure
As CMT1A therapies move toward clinical trials, researchers require established clinical networks capable of recruiting participants, collecting standardized data, and conducting multicenter studies. CMTA invests $1.2 million annually in the Inherited Neuropathy Consortium (INC), the world’s largest CMT clinical research network.
The INC spans 26 clinical sites globally, with more than 9,500 participants enrolled in its clinical registry, over 12,000 study participants and more than 200 published manuscripts. Through studies such as ACT-CMT and the development of outcome measures and biomarkers, the INC provides much of the clinical infrastructure supporting CMT1A trial readiness.
As new CMT1A therapies enter clinical development, the INC provides an established framework for evaluating them in well-characterized patient populations.
Industry Engagement and Support
The resources developed through CMTA-STAR support both investigator-initiated research and industry-led therapeutic development. So far in 2026, five biotechnology companies have accessed CMTA-STAR’s validated CMT1A preclinical models, expert contract research organization (CRO) network, and patient-derived stem cell lines through the CMTA-STAR Preclinical Toolbox. CMTA is also providing patient advocacy group support, including patient focus groups and surveys, trial design feedback, recruitment support, and key opinion leader input, to all CMTA Alliance Partner companies conducting active interventional clinical trials in CMT1A: NMD Pharma, Novartis, and ENCell, and others at earlier stages of development.
CMTA made recent investments in EverTree Bio and Armatus Bio to further support industry-driven development of CMT1A treatments.
Patient Engagement
Through CMTA’s Patients as Partners in Research platform, we have over 2880 CMT1A patient profiles, these are real people living with the disease today. Through the platform we connect individuals with opportunities to take part in research, lending their voice and in some cases their bodies, to support the development of new treatments. Treatments cannot be developed without the patient community firmly at the center and the Patients as Partners in Research platform facilitates patient focused drug development at every stage.
What Comes Next
CMTA continues to evaluate new opportunities to strengthen the CMT1A research ecosystem, with projects under consideration across all strategy areas described above.
Researchers and biopharmaceutical partners developing programs in CMT1A are encouraged to contact CMTA to explore opportunities for collaboration. To learn more about the CMTA-STAR Preclinical Toolbox, available CMT1A resources and to share patient participation opportunities, contact CMTA Chief Research Officer Katherine Forsey, PhD, at katherine@cmtausa.org.
