Research overview

The purpose of scientific research on spinal muscular atrophy is the discovery of effective treatment. This is an extraordinary challenge because the disease is caused by the lack of an essential protein, encoded by the gene SMN1. Most drugs used in treatment of diseases block the function of proteins, only few increase or replace it.

To win this important challenge is important to consider multiple approaches in order to increase the chances of success. It is as a game of hockey, where more shots on goal more likely to score.

The purpose of scientific research on spinal muscular atrophy is the discovery of effective treatment. This is an extraordinary challenge because the disease is caused by the lack of an essential protein, encoded by the gene SMN1. Most drugs used in treatment of diseases block the function of proteins, only few increase or replace it. To win this important challenge is important to consider multiple approaches in order to increase the chances of success. It is as a game of hockey, where more shots on goal more likely to score.

The research areas include: basic research on the function of SMN, model development and testing in vitro for the evaluation of compounds to increase the production of protein or correct the process of splicing, drug discovery research, treatment with stem cells and development of a rigorous system of measurement and evaluation protocols to be used in clinical trials, clinical research.

The main area and most promising is certainly the drug therapy, the discovery of a drug that is able to correct the genetic defect underlying the disease.
The main road to this goal is to increase, through the medicine, the role of SMN2 gene. In SMA patients both copies of the gene SMN1 are absent and / or changed. Fortunately there is a second copy, very similar, of SMN1 gene, located on the same chromosome. This gene is the SMN2 gene. It is also changed (this mutation affects all individuals and follows the trend of natural species), but if the effects of this mutation could be corrected, the gene could produce enough protein SMN to slow or reverse the disease process . Although the SMN2 gene is present in patients suffering from SMA, most of RNA messenger is not synthesized properly due to the mutation, which affects the process of splicing. The consequence is that only a small part of SMN2 protein is produced, precisely by that fraction of SMN2 mRNA synthesized correctly. Researchers are trying to find a therapeutic technique, by the increase of mRNA synthesized by SMN2 gene and by improving the process of splicing, in which the RNA transcript is converted into SMN2 mRNA SMN2.

The stem cell therapy is a promising way to treat spinal muscular atrophy. Stem cells are embryonic cells with the potential to generate neurons. The motor neurons of the spinal cord are created at the beginning of embryo development and therefore no longer replaced, as in other cells of the body that are replaced by new every few days. Recent studies on stem cells have found that it is possible to transplant these cells in the spinal cord, where they become motor neurons. Much work remains to be done before it is actually possible to transplant a large number of stem cells. But the biggest challenge is to find a method that allows the growth of axons from new motor neurons transplanted. In fact they will require a long-term growth from the spinal cord to the skeletal muscles.


Dr. Paolo Pisano