Dr. Chris Lorson and his colleagues have published a paper, “Optimization of Morpholino Antisense Oligonucleotides Targeting the Intronic Repressor Element1 in Spinal Muscular Atrophy,” in the journal Molecular Therapy.

The University of Missouri-based team is investigating ways to target SMN2, the SMA “backup gene.” Because of a genetic mutation in the SMN1 gene, individuals with SMA don’t produce survival motor neuron protein (SMN protein) at high enough levels. However, all individuals with SMA have at least one copy of SMN2, which typically produces a small amount of functional SMN protein. Lorson’s compound targets SMN2 and effectively “turns the volume up” for SMN2, allowing it to make more of the correct SMN protein.

“Our current treatment helps the body create a backup mechanism to combat the disease and extends survival in mice with SMA from just 13 days to a little over five months after only one injection at birth,” Lorson said. “This treatment helps produce the right form of SMN, the one that was only produced at very low levels before.”

In 2013, Cure SMA made a $150,000 grant to Dr. Lorson and Dr. Arthur Burghes, jointly, to fund research into this potential treatment approach. “Cure SMA was instrumental in providing the initial funding for this project. At the time, our lab knew that optimization of the sequence for our ASO was important, however, funding was not available to develop or test these new compounds. Cure SMA provided funding that allowed us to identify the optimized E1 ASO compound, screening a new panel of sequences, leading to the identification of our current lead candidate that can extend survival in SMA mice nearly 10-fold. Additionally, this work is exciting because it brings another type of chemistry to the fight against SMA – Morpholino chemistry. We are excited to continue to push this work closer to the clinic and we are grateful for the early stage funding received by Cure SMA and the families that support the SMA community,” said Lorson.

“We’re very excited about these results and the continued progress of this program,” said Jill Jarecki, PhD, Cure SMA’s chief scientific officer. “We know also that the entire SMA community shares in our excitement at seeing another promising treatment continue to move forward. Dr. Lorson’s project is part of a multi-prong strategy to attack SMA from all sides, looking at treatments that address the underlying genetics, including the SMN2 gene, and at treatments that protect the muscles and nerves. We eventually hope that these drugs can be used in combination to provide the best possible therapeutic effect.”

Dr. Lorson likewise agrees that it is unlikely a single compound will address the full gamut of symptoms. However, by combining therapies currently being researched, a better prognosis could be on the horizon, Lorson said.

The early-stage results of this research are promising. If additional studies are successful within the next few years, these compounds may be tested in human clinical trials with the hope of developing new treatments for SMA.

Pictured above: Dr. Lorson presenting at one of Cure SMA’s Family Friendly Research Poster Sessions.