image: Federico Herrera, Professor and reseacher at the Faculty of Sciences of the University of Lisbon (Portugal).
Credit: BioISI
A research team from the Cell Structure and Dynamics Laboratory of the Biosystems and Integrative Sciences Institute (BioISI) of the Faculty of Sciences of the University of Lisbon (CIÊNCIAS) (Portugal), led by Federico Herrera, has secured funding from Ataxia UK to investigate two rare neurological diseases in the ataxia category.
These are rare neurological disorders that affect balance, coordination and speech. It is estimated that, worldwide, 26 out of every 100,000 inhabitants suffer from one of the variants of this disease. “Although rare, they have dramatic consequences, because many of them affect babies and the diagnosis is difficult. Some families live decades without a correct diagnosis, making it difficult for them to be included in a group and to react to the disease”, explains Federico Herrera, researcher at BioISI and CIÊNCIAS.
The 12,000€ funding now awarded to Federico Herrera’s team will enable progress in the development of two projects that study two rare diseases that affect babies: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Spastic Ataxia 8 (SPAX8).
For the first study – “Towards a pharmacological model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)”, the CIÊNCIAS research team proposes to establish a pharmacological model to understand and test therapies for ARSACS that stand out for being more economical and easier to use.
In this rare disease, there is a loss of function of the sacsin protein, which in turn plays an important role in the organization of cellular structures called intermediate filaments, which are responsible for building the “skeleton” of cells (cytoskeleton) and which enable communication between nerve cells and muscle cells, leading to correct body movement. This model would be based on the use of a natural toxin – Withaferin A – which interferes with the formation of intermediate filaments, causing the same effects as the inactivation of the sacsin protein observed in the development of this ataxia.
The second part of the funding aims to support the work already underway within the scope of the project “Restoring NKX6-2 function by protein complementation: a proof-of-concept”, which aims to obtain a proof of concept. Assuming that Spastic Ataxia 8 (SPAX8) is caused by mutations that lead to the production of truncated (incomplete) versions of the NKX6-2 protein, which is relevant during the development of the baby, the researchers hope to be able to find the smallest fragment that is both non-functional per se and that becomes functional when joined to the fragment of the protein produced by the patient. This discovery will allow the disease to be modified with therapies that do not cause permanent changes in the genome of patients and will accelerate the advancement of therapies in the drug development pipeline. According to Federico Herrera, the impact of the knowledge produced with this funding will be quite significant: “These funds will allow us to shed new light on two rare diseases that are of little interest to the pharmaceutical industry, but which constitute two major scientific and biotechnological challenges”.
The two projects will be developed from September 2024 until September 2025, in the context of two doctoral theses in these areas. In the medium term, partnerships have not yet been established, but the research team remains in contact with the Portuguese Association of Hereditary Ataxias (APAHE) and the ARSACS Foundation, in order to monitor the development of the projects. An event is scheduled for September 25, the date that marks International Ataxia Day, which will bring together a vast community of clinicians, researchers, patients and associations interested in ataxias and other rare motor diseases.