Tiny DNA Molecule May Help Development of Myelin Repair Therapies, Study Suggests

Tiny DNA Molecule May Help Development of Myelin Repair Therapies, Study Suggests
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A shortened DNA molecule showed an increased ability to bind myelin in human cells, and may boost the development of remyelination approaches for multiple sclerosis (MS) treatment, according to a study.

The study, “Optimization of a 40-mer Antimyelin DNA Aptamer Identifies a 20-mer with Enhanced Properties for Potential Multiple Sclerosis Therapy,” was published in the journal Nucleic Acid Therapeutics.

Despite the availability of more treatments for MS, scientists are investigating potential approaches to restore the protective layer of nerve fibers, called myelin, which is progressively damaged in MS patients.

In this study, a team at Mayo Clinic College of Medicine and Science showed that a myelin-binding DNA aptamer — a small DNA molecule — known as LJM-3064 promoted remyelination in a mouse model of MS, and is rapidly distributed in the central nervous system (brain and spinal cord) as well as in other tissues of mice.

Compared with antibody-based approaches to induce remyelination, DNA aptamers are smaller, more stable, and easier and cheaper to produce. They also provide high target specificity and carry a low risk for immunogenicity, which refers to triggering an immune response.

The scientists shortened the original LJM-3064 from 40 to 20 nucleotides (the building blocks of DNA), hypothesizing that a specific portion of LJM-3064 was sufficient to bind myelin. A variant of this smaller molecule, called LJM-5708, showed increased myelin-binding ability.

LJM-5708 also retained the structure of the original 40-nucleotide compound. Importantly, the myelin-binding properties of LJM-5708 were preserved when the molecule was bound to a bacterial protein called streptavidin, which is key for improved body distribution and remyelination induced by aptamers in mice.

“These studies lay the framework for future testing of optimized remyelinating aptamer formulations in vivo,” the researchers wrote.

According to the team, the “optimized 20-nucleotide DNA aptamer LJM-5708 is thus a strong candidate for further preclinical testing, including … remyelination assay in vivo.” In particular, LJM-5708’s ability to specifically bind human cells makes it “a lead molecule for further investigation.”

‘The authors highlight the value of aptamer refinement of a therapeutic for multiple sclerosis treatment, and present a novel application for cell imaging,” Graham C. Parker, PhD, the journal’s executive editor, said in a press release.

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has studied Biochemistry also at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario, in London, Ontario. His work ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has studied Biochemistry also at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario, in London, Ontario. His work ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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