ALS gene therapy may enter the brain through HDO

For a long time, delivering any therapeutic drug to the brain has been a challenge.

Michelle Hastings studies genetic diseases at Rosalind Franklin University of Medicine and Science in Chicago, but she was not involved in the study

" Let drugs pass through the blood-brain barrier "

In 2015, a study published by Tokyo Takanori Yokota Medical and Dental University and his colleagues showed that a so-called heteroduplex nucleic acid molecule oligonucleotide (HDO) is composed of short DNA strands and modified bases.

In this new study, the research team showed that HDO designed for tumor-associated long non-coding RNA (Malat1) achieves higher levels of knockout in the brain and spinal cord.

"Double-stranded oligomers actually seem to be more easily delivered than single-stranded oligomers," said Frank Rigo, co-author of the study and vice president of functional genomics and drug discovery at Ionis Pharmaceuticals

" Oligonucleotide therapy is about to be approved "

After conducting a preliminary study on Malat1, the researchers generated HDOs of three clinically relevant genes:

DMPK, its mutation is related to a type of muscular dystrophy; glial fibrillary acidic protein (Gfap), which can cause Alexander disease; and human superoxide dismutase 1 (SOD1), when this enzyme is mutated and implanted in mice At that time, a model of amyotrophic lateral sclerosis can be established

"The data seems very powerful," wrote Rudy Juliano, professor emeritus at the University of North Carolina School of Medicine

"The first thing that shocked me was the huge dose they used

In this study, the author acknowledged the limitations of the current work, and Rigo said that the optimization plan is in place