Researchers at Shanghai Huashan Hospital have identified a novel therapeutic target that could lead to the world's first treatment to slow the progression of Parkinson's disease.
The discovery, published on Friday in the journal Science, centers on a protein called FAM171A2, which the researchers found plays a crucial role in the spread of pathological alpha-synuclein, a key protein involved in Parkinson's disease.
The team, led by Yu Jintai, conducted five years of clinical and basic research, including genome-wide association analysis of large-scale populations. They determined that FAM171A2 acts as an "intelligent recognition gate" on neuronal cell membranes, selectively binding to and inducing misfolding of pathological alpha-synuclein, ultimately leading to neuronal death.
Building on this discovery, the researchers used artificial intelligence to screen over 7,000 compounds and identified a molecule called Bemcentinib that effectively inhibits the binding of FAM171A2 to alpha-synuclein.
"Our study findings provide hope to block the spread of pathological alpha-synuclein and thus delay the progression of the disease by inhibiting the target FAM171A2 from the preclinical to clinical stage of the disease," Yu said.
Parkinson's disease, the second most common neurodegenerative disorder after Alzheimer's, affects millions worldwide. Current treatments focus on managing symptoms, such as tremors and muscle rigidity, but do not address the underlying disease progression.
The global prevalence of Parkinson's disease is projected to increase from around 7 million in 2015 to 13 million by 2040, with China accounting for approximately half the total number of patients worldwide.
Experts reviewing the study called the discovery a significant advancement, offering a promising therapeutic approach to block the spread of the pathology and postpone disease progression.
"This novel approach may complement existing treatments, such as using medications to replenish dopamine levels, and therefore improve motor ability in the clinical stage of the disease, and use deep brain stimulation later, paving the way for a more comprehensive treatment paradigm for Parkinson's disease," Yu said.
The research team has applied for an international patent for treating Parkinson's disease by targeting FAM171A2. They plan to focus on preclinical development of small molecule drugs, antibodies and gene therapy approaches over the next few years.
"Our first step is to expand the search for a possibly more efficient medicine to over 30,000 small molecule compounds. In the long run, we aim to advance such findings into clinical trials and applications," Yu said.
Researchers said that before this study, there were no functional experimental studies on the target protein.
"So further understanding of the physiological and pathological functions of this protein in the nervous system may also offer new therapeutic targets for other alpha-synuclein diseases, as well as neurodegenerative disorders such as Alzheimer's disease and dementia," Yu said.
