Researchers at the University of Miami, supported by the Charcot-Marie-Tooth Association (CMTA) and its Strategy To Accelerate Research (STAR) and led by CMTA-STAR Advisory Board member Mario Saporta, MD, PhD, have made significant progress in DNA-based therapeutics. Their groundbreaking work targets the fundamental genetic cause of CMT2E.
CMT2E is an axonal CMT (CMT2). Several different autosomal dominant mutations of the NEFL gene cause CMT2E. Dr. Saporta and colleagues specifically targeted the N98S mutation. This particular mutation might appear as “c.293A>G (p.Asn98Ser)” on your genetic test report if you have CMT2E.
For this project, the researchers developed a CMT2E model using cells that CMT2E community members donated. This model effectively replicates several biological symptoms and biomarkers associated with CMT2E, providing a solid foundation for exploring potential therapies.
Breakthrough in Antisense Oligonucleotide (ASO) Therapeutics
Recent advances in antisense oligonucleotide (ASO) therapeutics have shown immense promise in targeting genetically-caused diseases such as CMT. ASOs are like tiny pieces of genetic “tape” that can stick to faulty parts of a gene and fix them. This helps correct the gene’s instructions, and in the case of CMT2E, the researchers believe it might reduce or even stop the symptoms.
To evaluate the potential benefit of the ASO therapy, the researchers used both established and new biomarkers of peripheral nerve axonal degeneration to measure the effectiveness of the treatment. The results were promising, showing a significant decrease in clinically relevant biomarkers, and this has the potential to correlate with improving symptoms. This marks the first clinically viable genetic therapy for CMT2E, offering hope for an effective treatment where none previously existed.
Implications for Precision Medicine
The success of this ASO therapy strategy for CMT2E opens the door for similar approaches in treating other types of CMT. The researchers’ work demonstrates the potential of DNA-based therapeutics to provide targeted, effective treatments for CMT, significantly improving patient outcomes. This advancement highlights the promise of precision medicine in revolutionizing the management of CMT by tailoring treatments to the genetic profile of individuals.
Looking Ahead
CMTA continues to support and monitor the progress of this research with great interest. These findings’ implications can extend beyond CMT2E, highlighting the broader potential of ASO therapies to treat CMT. As the University of Miami team prepares to move into clinical trials, there is renewed hope for patients with CMT2E and other types of CMT.
This CMT2E project illustrates how CMTA’s commitment to uniting the community with clinicians and industry experts accelerates the advancement of treatments, bringing real impact and hope for a better future.
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Create Your Patients as Partners in Research ProfilePublished: July 18, 2024