Researchers develop novel therapeutic strategy to treat Huntington's disease

Researchers develop novel therapeutic strategy to treat Huntington's disease

Through an international joint research effort involving ProQR Therapeutics of the Netherlands, Université Grenoble Alpes of France and the KTH Royal Institute of Technology of Sweden, the research team of Professor Ji-Soon Song in the Department of Life Sciences and KAIST Institute for BioCentury of KAIST has established a noble strategy for treatment of Huntington's disease. The new work showed that the protein, converted from the disease form to its disease-free form, retains its original function and presents new obstacles to approaching Huntington's disease.

This study, co-authored by Hyeongju Kim, titled "A pathogen-proteolysis-resistant huntingtin isoform induced by an antisense oligonucleotide preserves huntingtin function," was published August 9, 2022, in the online edition of the Journal of Clinical Investigation Insight.

Huntington's disease is a dominantly inherited neurodegenerative disorder and is caused by a mutation in a protein called “huntingtin,” which adds to the protein a characteristic feature of an expanded stretch of glutamine amino acids called polyglutamine. It is estimated that one in 10,000 in the United States has Huntington's disease. Patients would suffer a decade of regression before death, and so far there is no known cure for the disease.

Cleavage near the stretched polyglutamine in mutant huntingtin is known to be the cause of Huntington's disease. However, because the huntingtin protein is required for the development and normal function of the brain, it is crucial to specifically eliminate the disease-causing protein while preserving those that still function normally.
The research team showed that huntingtin delta 12, the converted form of huntingtin that is resistant to the development of cleavages at the ends of the protein, the known cause of Huntington's disease (HD), relieves the symptoms of the disease while maintaining the functions of normal huntingtin.

The research was welcomed as it will certainly advance innovative strategies to combat Huntington's disease without altering the essential function of huntingtin.

This work was supported by a Global Research Lab grant from the National Research Foundation of Korea (NRF) and by a EUREKA Eurostars 2 grant from European Union Horizon 2020.

Source:

The Korea Advanced Institute of Science and Technology

Reference:

Kim, H., et al. (2022) A pathogenic proteolysis-resistant huntingtin isoform induced by an antisense oligonucleotide maintains huntingtin function. Journal of Clinical Investigation Insight. doi.org/10.1172/jci.insight.154108.

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