A new cell and gene therapy approach for Friedreich's ataxia

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 a 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 heart 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.

Meet the Principal Investigator(s) for the project

Professor Arturo Sala - Trained in Biochemistry and Cellular Biology at the University of Rome and the Italian National Institute of Health, I completed a PhD in Biochemistry at the University of Rome “La Sapienza” on the topic of DNA and RNA methylation in relation to muscle cell differentiation.  After a short postdoctoral training in the National Institute of Health in Rome, I won an international post-doctoral fellowship from the Italian Association for Cancer Research (AIRC) and moved to the Kimmel Cancer Institute, Thomas Jefferson University Philadelphia. Working in the laboratory of Prof. Bruno Calabretta, I was the first to characterize the transcription factor and oncoprotein B-MYB and establish its relationship with key tumour suppressor genes, such as p53 and retinoblastoma family members.  In 2001 I was recruited by the UCL Institute of Child Health as Senior Lecturer and later promoted to Reader. In UCL I continued to pursue the study of oncogenic transcription factors in the context of neuroblastoma, a childhood tumour affecting the peripheral nervous system. I was appointed Professor of Translational Cancer Research and Deputy Director of the Brunel Institute of Cancer Genetics and Pharmacogenomics in September 2011. In 2016 I joined the Synthetic Biology Theme in the Institute of Environment, Health and Societes. 

Related Research Group(s)

Inflammation Research and Translational Medicine - Driving scientific innovation and discovery for diagnosis, treatment, and management of cardiovascular disease, inflammatory and immune disorders, microbial resistance, and cancer.

Project last modified 27/09/2024