Synchrotron light for deciphering Friedreich's ataxia

The International Ataxia Awareness Day is held on the 25th September

- Projects, Research
  • The Neurogenetics research group, led by Dr Antoni Matilla is performing an experiment at the ALBA Synchrotron to obtain for the first time 3D images of cells with this disease. Friedreich's ataxia affects more than 3,000 people in Spain, causing serious mobility problems and other severe illnesses such as heart disease. At present there is no treatment to prevent or cure the disease.

Friedreich's ataxia is a rare neurodegenerative disease that progressively damages mobility, balance and coordination. It is an inherited disease, caused by a genetic mutation, that can appear when both parents are carriers.

The Neurogenetics Research group at the IGTP, ​​led by Dr. Antoni Matilla, is looking into the causes and possible treatments for this disease that results in high disability and an important decrease in the patients' quality of life.

"Today there is no treatment or cure for Friedreich's ataxia. It is necessary to try to understand how the disease develops in order to propose therapeutic solutions", says Dr. Ivelisse Sánchez, co-Principal Investigator of this project.

Researchers are now analysing donors' cells in the ALBA Synchrotron to see the changes caused by the disease.

Sneaking into cells

Friedreich's ataxia is caused by a defect in the FXN gene, which is responsible for encoding the frataxin protein, whose function is key for metabolising the iron. Frataxin is found in a wide variety of tissues (such as the cardiac tissue, spinal cord, liver or voluntary movement muscles). When this genetic mutation takes place, the production of frataxin decreases and causes a serious impact on the tissues.

Researchers from the IGTP have analysed cells from patients presenting a deficit of frataxin caused by the disease at the MISTRAL beamline of the ALBA Synchrotron. For the first time, 3D X-ray microscopy images have been obtained, allowing us to observe and compare the structural and morphological differences within them.

"Synchrotron light enables to image in three dimensions the changes occurring in whole cells, without the need of slicing them. No other technique can offer these results because it combines high resolution with the possibility of obtaining details of vitrified cells, that is, in an environment close to their native state", says Eva Pereiro, MISTRAL scientific leader. This beamline is one of the four instruments that exist worldwide to carry out this type of experiments.

"Our objective is to combine these data with pharmacological tests to evaluate their effectiveness and check whether they are able to restore the cellular functions affected by the disease," says Dr. Sánchez. The pre-doctoral researcher Eudald Balagué who is currently doing his PhD on Friedreich's Ataxia is also part of the team.

Living with Friedreich's ataxia

The International Ataxia Awareness Day is being held every year on the 25th of September to increase awareness and highlight the need to investigate and find prevention or curative treatments. First symptoms appear when patients are between 5 and 25 years old, presenting difficulties for coordinating movements or instability when walking. Ten years later, patients often need to use a wheelchair. In addition, most of them often also have heart problems, reducing considerably their life expectancy.

Currently there is no approved therapy and only palliative treatments can be offered. According to data from the Spanish Federation of Ataxias (FEDAES), it affects more than 8,000 people in Spain. To date, more than 100 different subtypes of inherited ataxia have been described. The IGTP Neurogenetics team is researching the genetic basis of ataxia for more than 10 years, identifying several subtypes of ataxia and elucidating the underlying molecular mechanisms. In particular, the group is studying Friedreich's ataxia since 2014 to develop a gene therapy against the disease.