Friedreich’s Ataxia (FA) is a genetic condition caused by mutations in the FXN gene. The mutation leads to a decrease in the production of frataxin protein causing progressive neuronal degeneration, loss of muscle control, fatigue, vision or hearing impairment, slurred speech, and heart problems. As FA is caused by mutations in a single gene, it might be treatable through a gene therapy approach.
How gene therapy works
Gene therapy consists of the intracellular delivery of genetic material to generate a therapeutic effect by correcting an existing abnormality or providing the cells with a new function.
Different types of gene delivery systems may be used in gene therapy to restore a specific gene function, such as viral and non-viral vectors.
Viral vectors are viruses that have been modified by deleting the harmful areas in their genomes, while non-viral vectors are physical and chemical systems, such as liposomes, nanoparticles, polymers, ultrasound, or laser-based or magnetic energy.
Non-viral vectors are advantageous in relation to viral vectors as delivery vehicles as they are simple to prepare and scale-up and usually have less pro-inflammatory effects than viral ones.
Gene therapy for Friedreich’s Ataxia
A gene therapy approach for the treatment of FA could be used either to correct the faulty frataxin gene or to correct any damage caused by the disease on other systems in the body such as the heart.
Central nervous system gene therapy
Voyager Therapeutics has a pipeline of investigational molecules to target severe diseases of the central nervous system, such as FA. They are currently starting preclinical tests to assess the safety and effectiveness of VY-FXN01, a lead candidate for the treatment of the neurological symptoms of FA.
Cardiac Gene Therapy
Earlier in 2014, mouse models of FA were used to demonstrate that gene therapy using a viral vector prevented and corrected cardiac damage. Researchers used an adeno-associated virus to introduce a normal gene into the heart tissue of mouse models of FA. This treatment restored heart function and reversed heart enlargement in mice that had already developed heart failure, a symptom seen in people with FA.
Improving the delivery of gene therapy into cells
A project supported by GENEFA, a platform for an FA cure, is investigating ways to modify vectors to improve their delivery across the blood brain barrier (BBB). By generating modified viral vectors and virus-free synthetic nanoparticles the aim is to make the DNA delivery into the nervous system more efficient. It is hoped that these nanosystems will cross the BBB thanks to the peptides that are able to cross them (referred to as BBB-shuttles).
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