C9orf72 gene therapy

Summary

Mutations in the C9orf72 gene are the most common genetic cause of MND, accounting for about 40% of familial (inherited) and 7% of sporadic (not inherited) cases. Researchers have previously tried to silence the faulty C9orf72 gene using the same approach as used for SOD1 with tofersen. However these attempts have failed, highlighting the complexity of C9orf72 biology and the need for a different approach.

Dr Lee’s team is using special harmless viruses called adeno-associated viruses (AAV) to deliver tiny molecules known as microRNAs and small nuclear RNAs to motor neurons. These molecules will target multiple problematic parts of the C9orf72 gene, to ensure that the mutant gene no longer works. The team then plans to reintroduce a modified healthy version of the C9orf72 gene, to restore the normal function of motor neurons. This innovative approach is different from previous attempts and aims to address the negative effects of the C9orf72 gene at both the genetic and cellular levels.

Why this research is important

If successful, Dr Lee's research could lead to a new gene therapy for a specific population of people living with MND, addressing the disease at its genetic root. This approach also holds promise for Frontotemporal Dementia (FTD) treatment, given the shared genetic factors. Importantly, even if the desired outcomes aren't fully achieved, the study will significantly enhance our understanding of C9orf72 biology, contributing valuable insights to the field.

To find out more about this project, read our in-depth article here. 

To learn more about gene therapies, check out our infographic.