Research highlights
Questions, findings and their significance, from the Balmus Laboratory and our collaborators.
Why some neurons are more vulnerable to inflammation
Morcom, Xia and colleagues
Human tissue, cell models and mouse studies- 01Neuroinflammation
- 02DNA damage burden
- 03Selective neuronal vulnerability
The question
Why does inflammation damage some types of neuron more than others?
What we found
Working with collaborators, we found a high burden of DNA damage in CUX2-positive cortical neurons in multiple sclerosis tissue and experimental models. CUX2 and ATF4 supported repair and neuronal resilience.
Why it matters
The results connect a cell’s capacity to repair DNA with its vulnerability to inflammatory injury, helping define mechanisms to investigate for neuroprotection.
Read the paper: DNA damage burden causes selective CUX2 neuron loss in neuroinflammation
Slowing the expansion of a disease-causing DNA repeat
Bunting, Donaldson and colleagues
Patient-derived neurons and target engagement in mice- 01Lower MSH3
- 02Reduce repeat expansion
- 03Test therapeutic potential
The question
Can reducing a DNA repair protein slow the expansion of the Huntington’s disease repeat?
What we found
In a collaboration led by Sarah Tabrizi’s team, an antisense oligonucleotide lowered MSH3 and stalled CAG repeat expansion in patient-derived striatal neurons. Target reduction was also demonstrated in a humanised mouse model.
Why it matters
The findings support MSH3 as a target for further therapeutic development. This is preclinical evidence; benefit in people remains to be established.
Modelling early disease in human brain organoids
Szebényi and colleagues
Patient-derived cortical organoid slice cultures- 01Patient-derived stem cells
- 02Organoid slice cultures
- 03Study and target early pathology
The question
How can we investigate early ALS/FTD changes in human brain cells?
What we found
Together with András Lakatos’s group, we studied patient-derived cortical organoid slices. These revealed distinct disturbances in astroglia and neurons, including DNA damage. A compound rescued several neuronal abnormalities in the model.
Why it matters
The system provides a way to study early disease mechanisms and test potential interventions. Results in organoids do not establish a treatment for patients.