Dr Federico Herrera, based at the University of Lisbon, Portugal, has recently shared the results of his Ataxia UK-funded project, ‘Towards a pharmacological model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)’.
ARSACS is a rare form of ataxia caused by the loss of function of a protein called sacsin, which is thought to be due to the inactivation of the sacsin gene that codes for the sacsin protein. Sacsin proteins are needed to organise filament structures that make up part of the scaffolding of cells called the cytoskeleton. These filaments, known as intermediate filaments, help nerve cells to communicate with each other, and with muscle cells, needed for movement. Dr Herrera and his team have previously shown using animal and human cell models that changes in intermediate filaments, as well as in the energy centres of cells called mitochondria, are key features of ARSACS.
A drug called Withaferin A (WFA) could mimic the cellular effects caused by inactivation of the sacsin gene in ARSACS. In this project, the researchers treated animal and human cells with WFA to observe its effects on the cell cytoskeleton and mitochondria. The team compared results from their WFA model of ARSACS to results from their genetic models of ARSACS. The researchers proposed that this could be a new, easy to use, model to study ARSACS and could be used to test therapies for the condition.
Unfortunately, whilst their results showed that adding WFA did lead to significant sacsin loss and collapse of the cytoskeleton and mitochondrial networks, they did could not find any more similarities at the molecular and cellular levels with cells lacking sacsin, the genetic model of ARSACS. This could indicate that part of the alterations found in the genetic model of ARSACS were not due to cytoskeleton or mitochondrial collapse.
However, the project allowed the researchers to learn more about ARSACS, and the group has received further funding from the ARSACS Foundation in Canada to continue their studies on this disorder. The project also led to the first ‘meeting on Ataxias, Leukodystrophies and other Rare Neurological Disorders’ in Portugal – a forum for patients, associations, clinicians, and researchers in these disorders to come together and exchange information, ideas and experiences. There has since been a second meeting.
Read an interview with Dr Herrera on this project here.
