The genetic alteration that causes Machado-Joseph Disease (MJD/SCA3) was identified in 1994. Since 1996 that a genetic test, which detects the presence of the altered (mutated) gene, is available. It is known that if the mutated gene is present, the carrier will develop MJD/SCA3. Nevertheless, the presence of the mutated gene is not enough to explain the differences in the clinical manifestations that appear in the various patients, in particular with regard to the age of onset, which ranges from 4 to 70 years. Thus, it is expected that there are other genes which influence the behavior of the main gene; most of these genes, called "modifier genes", remain unidentified for MJD/SCA3. The identification of genetic modifiers would enable improvement in the prediction of the age of onset, also allowing a better understanding of the altered mechanisms in MJD/SCA3. The knowledge about the genes that control the clinical expression of the disease, namely its age of onset, will have a potential impact when therapies are available. In fact, clinical trials that are currently being conducted in diseases similar to MJD/SCA3 show that the drugs will have their maximum efficacy if administrated in the beginning, or even, before the onset, so its prediction improvement is acknowledge.

The EXOS3 project aims to identify modifier genes in MJD/SCA3.

Using a very recent genetic analysis technology (Exome Sequencing), the EXOS3 team will analyse the DNA portion that contains the most relevant information (exome). After the laboratory analysis, they will apply a series of statistic procedures in order to understand which genes are influencing the way the disease manifests itself.