Gene therapy holds real promise for certain types of Charcot-Marie-Tooth disease (CMT), a hereditary peripheral nerve disorder. Not all CMT subtypes are candidates, but HNF has identified several where the underlying genetic defect may be addressable through gene therapy. HNF is leading efforts to identify those subtypes and is working with a collaborative team of experts to advance research.

HNF selected its first three CMT types based on their potential for success. If you are a patient or know someone with one of the following types, please contact HNF through the website contact form.

CNTnap1

This rare and severe recessive form of CMT involves loss of the CNTnap1 gene and its protein product, CASPR. CASPR helps anchor the insulating (myelin) cells to the signal-transmitting nerve cell axons. When this protein is missing, the development and maintenance of many nerve fibers in both the central and peripheral nervous system are profoundly disrupted.

James was born with CNTnap1 and was unable to breathe at birth. He was immediately intubated and transferred that night to a children’s hospital specializing in rare diseases. HNF has been working to raise funds to support research that could help James and others like him. To learn more about his story, visit James' Cure.

CMT4 (GDAP1)

CMT4 is a subtype of CMT inherited in an autosomal recessive pattern, meaning a person must inherit a changed copy of the gene from each parent to be affected.

Estela Lugo, HNF Medical Outreach Director, and her sister Melissa were both diagnosed with CMT at age 3. For many years their specific subtype remained unconfirmed, as earlier genetic tests were inconclusive. Working at HNF highlighted the importance of pursuing a precise genetic diagnosis, and more recently Estela and Melissa received a confirmed diagnosis of CMT4 GDAP1. Estela shared her experience in a heartfelt testimony at the Externally-Led Patient-Focused Drug Development Meeting held by the FDA. To watch Estela’s testimony, visit hnf-cure.org/cmt4-gdap-gene-therapy.

CMT6 (c12orf56): One Gene, Two Diseases

Mutations in the C12orf56 gene can cause two distinct conditions: CMT6 and Leigh’s Syndrome. Both involve dysfunction of the mitochondria, the structures inside cells that produce energy, and both can be progressive and severe.

CMT6 is a complex subtype associated not only with typical CMT symptoms but also with features that may include delayed learning, vision loss, language impairment, and shorter life expectancy. In some patients, the same gene mutation can trigger Leigh’s Syndrome, a more aggressive central nervous system disease. Symptoms of Leigh’s are often triggered by a viral infection and may include developmental delay or regression, loss of coordination, vision and hearing loss, memory disturbance, and reduced muscle tone.

HNF has been working to raise funds for Zachary Houliares, age 21 at the time of reporting, and others like him. Despite his challenges, including legal blindness, Zachary had excelled in his community as a coach for his high school sports team and was continuing that work at the college level. After contracting the flu, he experienced a severe decline that led to a diagnosis of Leigh’s Syndrome. He was hospitalized and was slowly recovering.

HNF is working on developing a gene therapy for these diseases in collaboration with Robert Burgess, PhD, at Jackson Labs, Steven Gray, PhD, at UT Southwestern, and Mario Saporta, MD, PhD, MBA, at the University of Miami.

“As genetic therapies quickly become a real option for CMT patients, these new HNF projects are very exciting for patients, physicians, and researchers alike.”, Dr. Stephan Züchner, MD, PhD, Professor for Human Genetics and Neurology, Chair of the Dr. John T. Macdonald Foundation Department of Human Genetics, Co-Director of the John P. Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine, and Founder of The Genesis Project, a key collaborator of HNF’s Gene Therapy Research initiative

To learn more, visit www.curecmt.org.