Friedreich's ataxia is a rare disease caused by mutation of the Frataxin gene (FXN). This results in dramatically reduced levels in the tissues of patients of a protein essential for life called Frataxin.
Children born with the defective version of the FXN gene by the age of 5 to 10 years start to manifest the symptoms of the disease that include gradual loss of strength and sensation in the arms and legs; muscle stiffness (spasticity); and impaired speech, hearing, and vision. Individuals with Friedreich's ataxia develop muscle weakness and often have a form of heart disease called hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle and can be life threatening.
The average life expectancy is 37 years and there is still no definitive cure for the condition. Standard management is mainly symptomatic and based on physiotherapy, to alleviate difficulty on speech or swallowing, surgery, for severe cases of scoliosis or foot deformities, and medication to control hearth arrhythmias.
The experimental approach that we are using in our laboratory to tackle the condition is based on cell and gene therapy. We aim to restore appropriate levels of the Frataxin protein by engineering a new version of the FXN gene that will be inserted in the DNA of blood forming (stem) cells. The blood stem cells will deliver the therapeutic protein to the heart, the brain and other tissues that are particularly sensitive to the loss of Frataxin. Since the therapeutic protein will be produced by stem cells that are permanently homed in the bone marrow of patients, the treatment should result in the cure of the condition. Before testing this strategy in patients, we need to demonstrate its efficacy in a mouse model of Friedrich's ataxia that was developed in our laboratory. We will conduct a clinical trial in mice using appropriately modified FXN genes that will be introduced into blood cells. The modified cells will be injected into mice and the progression of the disease will be compared between treated and control animals. If our strategy will be successful in the laboratory, this will justify the start of a clinical trial in patients with Friedrich's ataxia.