Molecule Shows Potential to Treat Mild Cases of SMA in Early Study

The molecule A15/283, developed to treat spinal muscular atrophy (SMA), has shown significant efficacy in male mouse models of the disease, a new study shows.

The study, “Gender-Specific Amelioration of SMA Phenotype upon Disruption of a Deep Intronic Structure by an Oligonucleotide,” appeared in the journal Molecular Therapy.

SMA is caused by low levels of the survival motor neuron (SMN) protein, usually as a result of a genetic mutation. Critical to the proper functioning of spinal motor neurons, SMN regulates expression of certain vital genes.

Researchers at Iowa State University have identified a molecule, A15/283, to treat SMA. A15/283 is an antisense oligonucleotide, or a DNA sequence that binds to mRNAs, which are the intermediary molecules between the DNA and the protein.

Since mRNAs must be single-stranded in order to become “translated” into proteins, the binding of the antisense oligonucleotide to mRNA molecules renders the mRNA unable to be turned into a protein, as the molecule is now double-stranded. Using this technique against a degradation protein that would otherwise degrade SMN will likely boost SMN levels.

Researchers gave A15/283 to mouse models of SMA lacking the SMN protein one and again three days after birth. Mice with SMA have various symptoms including death of the tail, deficient testicle growth and decreased sperm production.

Results showed gender-specific improvement of tail necrosis in male mice. Researchers also observed a modest increase in SMN protein levels, leading to significant improvement in testicular development and sperm production.

Researchers also analyzed levels of certain genes involved in the development of adult testes and concluded that early administration of A15/283 led to a near-total correction in expression levels due to increases in the SMN protein.

“These results in the mouse model are very promising for the possible treatment of mild spinal muscular atrophy cases in children,” Dr. Ravindra Singh, a professor of biomedical sciences at Iowa State’s College of Veterinary Medicine, said in a press release. “We’re hoping this line of research could someday lead to clinical trials, but more work remains before that can happen.”