From the press release by Cold Spring Harbor Laboratory:

CSHL researchers demonstrate efficacy of antisense therapy for spinal muscular atrophy

Chemically modified RNA segments called ASOs delivered into spinal cords of adult and neonatal mice provide a long term rescue from disease symptoms

Cold Spring Harbor, N.Y. - The devastating, currently incurable motor-neuron disease spinal muscular atrophy (SMA) might soon be treated with tiny, chemically modified pieces of RNA called antisense oligonucleotides (ASOs).

Scientists at Cold Spring Harbor Laboratory (CSHL) and California-based Isis Pharmaceuticals have succeeded in reversing symptoms of Type III SMA, a relatively mild form of the disease, in mice by introducing an ASO into their spinal cords. The ASO fixes the molecular mistake underlying SMA by redirecting a cellular editing process called alternative splicing.

“Validating ASO efficacy in animal models is a crucial pre-clinical step before this strategy can be applied in SMA patients,” says CSHL Professor Adrian Krainer, Ph.D. “We have now successfully demonstrated this therapeutic efficacy in the mouse nervous system. Although the mice only have the mild symptoms of Type III SMA, our treatment can effectively correct them.”

Based in part on the team’s findings, which appear online ahead of print on July 12th in Genes and Development, Isis selected an antisense drug candidate to move forward in development to treat SMA.

“SMA is the leading genetic cause of infant mortality and has limited treatment options for patients. With Dr. Krainer’s lab at Cold Spring Harbor Laboratory, we have made significant progress in identifying a drug development candidate and conducting early preclinical studies to access its therapeutic potential,” said Frank Bennett, Ph.D., Senior Vice President of Research at Isis Pharmaceuticals. “We are committed to advancing this program toward the clinic.”

To read the full press release, click here.

To read the abstract of the study, click here.

Dr. Adrian Krainer is a friend of FightSMA and a regular speaker at FightSMA’s Annual Conference. At the 2010 FightSMA Annual Conference, his presentation was entitled “Antisense Correction of SMN2 Splicing in the CNS for SMA Therapy.”

From the press release by Cold Spring Harbor Laboratory:

November 4, 2009

Researchers identify drug candidate for treating spinal muscular atrophy

Cold Spring Harbor, N.Y. – A chemical cousin of the common antibiotic tetracycline might be useful in treating spinal muscular atrophy (SMA), a currently incurable disease that is the leading genetic cause of death in infants. This is the finding of a research collaboration involving Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory (CSHL) and scientists from Paratek Pharmaceuticals and Rosalind Franklin University of Medicine and Science.

SMA is caused by mutations in a gene called Survival of Motor Neuron 1 (SMN1), resulting in a decrease in the levels of SMN protein in the motor neurons of the spinal cord – the cells that control muscle activity. Without the protein, these neurons degenerate, and infants born with the mutations progressively lose the ability to move, swallow, and breathe. There are no approved therapies for the treatment of SMA, which affects approximately 1 in 6,000 babies born in the United States.

The new molecule boosts the levels of SMN protein in cells by fixing a mistake in a cellular processing mechanism called RNA splicing. In a study that will appear in the journal Science Translational Medicine on November 4th, the scientists report this fix in both mouse models of SMA, as well as in cells isolated from SMA patients.

Unlike previously identified molecules that stimulate SMN production, the tetracycline-like compound is a unique therapeutic candidate in that it is a small molecule that specifically alters RNA splicing by directly targeting the splicing reaction.

To read the full press release, click here.

To read the abstract of the study, click here.

Dr. Adrian Krainer is a friend of FightSMA and a regular speaker at FightSMA’s Annual Conference. At the 2009 FightSMA Annual Conference, he spoke on subject of splicing and SMA.