Stop Parkinson's Disease Before It Starts

Osaka, Japan – A research team led by Osaka University recently released results that offer a glimmer of hope to the millions of people with Parkinson's disease around the world. Although more prevalent in the over-sixties, PM can strike at any age, with an estimated prevalence of 41 out of 40. And although it is not fatal in itself, the progressive neurodegeneration that characterizes PD can often cause side effects that can lead to death.

The exact cause of Parkinson's disease remains a mystery, but researchers believe that genetics and the environment will probably play a role. It is however important to note that all patients with PD exhibit a loss of dopaminergic neurons in the brain and an increase in levels of a protein called α-synuclein, which accumulates in Lewy bodies. Lewy bodies are a pathological feature of familial and sporadic forms of the disease, as well as some types of dementia.

In the study published this month in Scientific reportsThe team led by researchers at Osaka University's Graduate School of Medicine focused on a-synuclein as a target for a new treatment for PD.

"Although some drugs treat the symptoms associated with PD, there is no basic treatment to control the onset and progression of the disease," says lead author Takuya Uehara. "Therefore, we sought ways to prevent the expression of α-synuclein and effectively eliminate the physiological cause of PM."

To do this, the researchers designed short DNA fragments that are mirror images of sections of the α-synuclein gene product. The constructs were stabilized by the addition of amido bridging. The resulting fragments, referred to as amido-bridged nucleic acid modified antisense oligonucleotides (ASO), bind to their corresponding mRNA sequence, preventing its translation into protein. After examining 50 different ASOs, the researchers opted for a 15-nucleotide sequence reducing by 81% the levels of α-synuclein mRNA.

"When we tested the ASO in a mouse model of PD, we found that it was administered to the brain without the need for a chemical vector," said Chi-Jing Choong, co-lead author. . "Additional tests showed that ASO effectively reduced α-synuclein production in mice and significantly reduced the severity of symptoms of the disease within 27 days of administration."

Lead author of the study, Hideki Mochizuki, explains: "Our results showed that gene therapy using ASOs targeting α-synuclein is a promising strategy for the control and prevention of MP We hope that in the future, this method will be used not only successfully treat PD, but also dementia caused by the accumulation of a-synuclein ".

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This work was supported by the Japan Agency for Research and Medical Development (AMED) under grant number JP17ek0109195.

The article, "Antisense oligonucleotides modified by an amido-bridged nucleic acid (AmNA), targeting α-synuclein as a new treatment for Parkinson's disease," was published in Scientific reports at DOI: 10.1038 / s41598-019-43772-9.

About the University of Osaka

Osaka University was founded in 1931 as one of Japan's seven imperial universities and has now expanded to one of Japan's leading comprehensive universities. The university is today the most innovative in Japan and one of the most innovative institutions in the world according to the Top 100 Innovative Universities of Reuters 2015 and Nature Index Innovation 2017. The capacity of the # 39 university to innovate from the stage of basic research through the creation of useful technologies with an economic impact stems from its broad disciplinary spectrum.

Website: https: //resou.Osaka-u.acjp /in /top