Diseases that affect the brain and spinal cord can be particularly devastating, and finding new and more effective ways to treat these conditions is an important goal for researchers and clinicians alike. Now, a research group from Japan reports that slightly modifying an existing treatment for central nervous system (CNS) disease dramatically increases its effectiveness. In a study published recently in Molecular Therapy Nucleic Acids , researchers from Tokyo Medical and Dental University (TMDU) and Osaka University have revealed that adding a modified sugar to antisense oligonucleotides (ASOs), a recently developed treatment strategy for CNS disease caused by toxic proteins, greatly decreases disease symptoms.
Multiple ASOs have been approved for clinical use, including gapmer ASOs, which are small pieces of genetic material binding to RNA messenger molecules that produce mutant disease-causing proteins to flag them for degradation. Modifying the chemical composition of these gapmer ASOs can both increase their ability to target molecules for degradation and decrease the toxic side effects of the treatment. "We recently developed a new chemical modification called BNAP-AEO," says lead author of the study Taiki Matsubayashi.
"While ASOs carrying BNAP-AEO are expected to be highly effective, their biological efficacy and toxicity have not been investigated." To characterize gapmer ASOs modified by the inclusion of BNAP-AEO, the researchers first evaluated the stability of gap.
