Next generation DNA-like molecule for the treatment of spinal muscular atrophy
Spinal muscular atrophy (SMA) is a devastating genetic disease affecting many children. SMA is the most common cause of infantile death in Canada and worldwide. SMA type 1 is the most common and severe form of the disease. Most children with type 1 SMA live only a few years. The disease affects bodywide nerves to move muscles. Most patients die due to complications with breathing. SMA is caused by an error in a genetic code of a gene called survival of motor neuron 1 (SMN1). With an error in this gene, patients are no longer able to produce an essential protein for survival called SMN. Humans uniquely have a nearly identical copy of the SMN1 gene known as SMN2, that is capable of producing approximately 10% of the much-needed SMN protein, allowing children to survive long enough to be born. This biological miracle is, however, short-lived, as 10% is not enough to remain healthy. SMA is the result of our body's messenger system being tricked by a couple of faulty letters in the gene. For proper production of the SMN protein, our cellular machinery first must read a message sent from our DNA. In the SMN2 gene, this message is written incorrectly, but only a small part of the message is incorrect. We will use a new technology, DNA-like molecule, that acts like a molecular Band-Aid to cover up the mistake in the message. Covering the mistake allows the machinery in charge of making protein to properly read the message, and ultimately use that message to produce normal levels of proteins. We have designed and tested several types of molecular Band-Aids, some of which were able to restore near normal levels of SMN in patients' cells and improved symptoms in mice. Two key challenges faced in clinical trials are delivery of the molecular Band-Aid into cells, and the harmful effects some of them have on our bodies. Our goal is to develop a safer and more effective molecular Band-Aid and demonstrate their ability to cure mice with SMA. One day we hope that the wounds on SMA patient's genes can be covered up, and their bodies can heal.