The Charcot-Marie-Tooth Association (CMTA) has announced a $240K investment in a groundbreaking gene replacement therapy for CMT4A, with potential applications for other types of CMT. This critical project is led by Xin Chen, MD, PhD, and CMTA Scientific Advisory Board member Steven Gray, PhD, at the University of Texas Southwestern Medical Center in Dallas, Texas. This investment aligns with CMTA’s strategic imperative to support research that has broad and significant impacts for community members.
CMT4A is a severe demyelinating type of CMT caused by recessive GDAP1 gene variants. This project aims to design and test an adeno-associated virus 9 (AAV9) vector to replace the faulty GDAP1 gene with a fully functional version. Drs. Chen and Gray will conduct their experiments using a model replicating CMT4A. If successful, this approach could serve as a template for treating other types of CMT, such as CMT4B1 and CMT4D.
“Recent advances in developing desirable AAV capsids, optimizing genome designs, and harnessing modern biotechnologies have dramatically contributed to the growth of the AAV gene therapy field,” said Dr. Chen. “With these constantly evolving and improving AAV vector technologies, we believe that studies with relatively rare forms of CMT, such as CMT4A, can provide proof-of-concept for rapidly developing CMT gene therapies. As better AAV vector technology becomes available, we can expand the reach of this ‘templated’ approach to more forms of CMT.”
Through the Strategy To Accelerate Research (STAR) initiative, CMTA has been at the forefront of accelerating gene replacement therapies for CMT, underscoring our leadership in this critical area of research,” said Katherine Forsey, PhD, CMTA Chief Research Officer. “This investment in gene replacement therapy represents a significant step towards developing a roadmap for rapidly translating treatments for CMT into clinical trials. By leveraging advanced AAV vector technologies, we create a blueprint for future therapies, bringing hope to the broader CMT community.”
In recent research, scientists tested an AAV9 vector designed to carry the GDAP1 gene across the central nervous system in a CMT4A model. This early proof-of-concept study aimed to evaluate the potential effectiveness and safety of GDAP1 gene transfer. The preliminary results are promising: a single dose of the AAV9 vector demonstrated safety and effectiveness in improving physical performance and nerve conduction velocity with the CMT4A model.
Further work is underway to confirm these preliminary findings. If these studies continue showing favorable effectiveness and safety, this approach could follow the precedent set by successful projects targeting giant axonal neuropathy (GAN) and CMT4J. This progression could lead to additional preclinical studies and, eventually, the translation of this gene therapy approach into human treatments.
If successful, this project for CMT4A could pave the way for expanding this “templated” approach to more forms of CMT, offering hope for effective treatments for a broader range of CMT patients.
CMTA’s commitment to exploring innovative therapies highlights its unwavering dedication to improving the lives of those affected by CMT. By fostering collaborations between the CMT community, clinicians, and industry experts, CMTA continues to lead the charge in accelerating research and bringing hope to patients worldwide.
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Create Your Patients as Partners in Research ProfilePublished: July 31, 2024