"exploringthe pathophysiology of KCTD11-related CMT neuropathy" charcot- marie - tooth disease (CMT) is the most common inherited peripheral neuropathy, affecting 1 in 2,500 individuals

The National Institute of Neurological Disorders and Stroke awarded Albany Medical College $164,000 on August 10, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to explore the pathophysiology of KCTD11-related Charcot-Marie-Tooth neuropathy.

The project investigates how mutations in KCTD11 cause recessive intermediate CMT (RI-CMTE), a peripheral neuropathy characterized by progressive neurological decline and abnormal myelination. CMT is the most common inherited peripheral neuropathy, affecting approximately 1 in 2,500 individuals, yet no disease-modifying therapies exist. The work will generate patient-relevant experimental models combining genetic, cellular, and molecular approaches to determine whether KCTD11 dysfunction primarily arises from Schwann cell dysfunction, motor neuron vulnerability, or both. The research will investigate how KCTD11 deficiency compromises myelin integrity and axon-glial communication, clarify the cellular origins of RI-CMTE, and define pathways destabilized by KCTD11 mutations. The proposed work will deliver the first mechanistic framework for KCTD11-related neuropathy and provide a community resource for studying this newly recognized disease subtype.

The award period runs from August 10, 2026, through July 31, 2028, with performance at Albany Medical College in Albany, New York.

Despite the identification of more than 125 causative genes, disease remain poorly understood and no disease-modifying therapies exist. Recently, mutations in have been discovered as the cause of a novel recessive intermediate form of CMT (RI-cmte). Patients with progressive neuropathy and abnormal myelination, but the cellular and molecular basis of disease unknown. Unclear models progress. Peripheral KCTD11 by neuropathy, recognized studies suggest that loss of KCTD11 function disrupts peripheral nerve homeostasis, yet IT is whether this results primarily from schwann cell dysfunction, motor neuron vulnerability, or both. Current are insufficient to dissect these contributions, limiting mechanistic understanding and preclinical this project will generate new, patient-relevant experimental models to study the role of KCTD11 in nerve biology. By combining genetic, cellular, and molecular approaches, we will investigate how deficiency compromises myelin integrity and axon-glial communication. Studies are designed to clarify t he cellular rigins of RI-cmte, define the pathways destabilized KCTD11 mutations. The proposed work will deliver the first mechanistic framework for KCTD11-related fill a critical GAP in CMT research, and provide a community resource for the study of this newly disease subtype. Preliminary these o