TMDU researchers demonstrate proof of concept of antisense nucleic acid therapy to prevent the spread of α-synuclein pathologies in synucleinopathies. Parkinson's disease (PD), as well as many other neurodegenerative disorders, has shown a link between the abnormal aggregation of a protein called α-synuclein (aSyn) and neuronal death. These aggregates, known as Lewy bodies and Lewy neurites depending on their subcellular localization, can spread by continuously causing normal endogenous aSyn to misfold.
The complex nature of this aggregation process poses significant challenges in disease management. Now, promising research from scientists in Japan suggests potential breakthroughs in developing effective treatment strategies for PD. In a study published in Volume 12, Issue 75 of the journal Acta Neuropathologica Communications on May 14, 2024, a research team from Tokyo Medical and Dental University (TMDU) explored the use of antisense oligonucleotides (ASOs) to reduce the expression of aSyn and improve symptoms in a mouse model of PD.
ASOs are compounds that can be engineered to induce the target mRNA-specific degradation, which in turn decreases the levels of its corresponding protein. Even though they are not the only drugs that can control the expression of aSyn, ASOs have a crucial advantage over other approaches, as lead author Professor Tetsuya Nagata explains: "Currently, antibody drugs and vaccines targeting aSyn are under development for aSyn-related neuropathies,.