Dr Federico Herrera of the University of Lisbon, Portugal, has recently shared results of his Ataxia UK-funded project, ‘Restoring NKX6-2 function by protein complementation: a proof-of-concept’.
Spastic ataxia 8 (SPAX8) is caused by mutations in a gene called NKX6-2 that result in the formation of incomplete NKX6-2 proteins which are missing fragments. This leads to the NKX6-2 proteins becoming dysfunctional. NKX6-2 proteins are involved in interacting with DNA and controlling production of certain proteins in the central nervous system.
Current evidence suggests that protein function due to mutations of this type can be restored by adding the missing fragments, in a process known as protein complementation. In this project, Dr Herrera and his team proposed that protein complementation can be applied to mutations that lead to incomplete NKX6-2 proteins.
The team created two fragments of the NKX6-2 protein and combined them with the smallest SPAX-8-associated NKX6-2 fragment in human living cell lines. They wanted to know whether this combination of fragments recovered normal NKX6-2 function. They found that protein complementation was possible, with some positive changes such as more NKX6-2 localising to the nucleus, the part of the cell where DNA is found, but they were not able to fully recover NKX6-2 function. The researchers hoped that by studying the structure and function of the NKX6-2 protein, they can pave the way for the development of possible therapies for SPAX8. For now, these tools still need fine-tuning, but show promise. The group hope to continue this work.
This project was made possible by a generous donation from the DVS Foundation.
Read more about the project in an interview with Dr Herrera here.
