It is a promising therapeutic target that researchers from the University of California in Los Angeles (UCLA) reveal in vascular dementia. Scientists discovered, in mice, how the brain could stop inflammation of blood vessels and induce recovery. Their resultspublished in Celltherefore show how inflammation of the vessels exacerbates damage caused by vascular dementia and demonstrate that targeting this process can promote brain repair, or even functional recovery. To date, there is no drug treatment that can promote the healing of vascular dementia.
Vascular dementia is the second cause of dementia – after mixed dementia where vascular dementia associates with Alzheimer’s disease – and finds a fertile soil in cardiovascular disease. It usually occurs after one or more cerebral vascular accidents, favored themselves by high blood pressurediabetes, atherosclerosis, hyperlipmerics or smoking. Public health France reports as such that maladies cardio-neurovasculaires were responsible for more than a million hospitalizations in 2022 and 140,000 deaths in 2021 (one in five deaths), and that only one in ten French people had optimal cardiovascular health. On the other hand, the 65-84 year olds represented more than half of the cases of stroke in 2022.
Two identified molecular systems
In vascular dementia, initial brain lesions gradually gain the surrounding tissues. It is by taking an interest in these expansion areas in murine models that researchers have identified all the molecules that allow cells to communicate (Interactoma).
The team then wanted to know which had a high or low activity compared to the normal brain. And scientists have thus identified the CD39/A3AR molecular system as potentially important. In vascular dementia, the CD39 (an enzyme) and the A3 receptor of adenosine (A3AR) are regulated downwards in these two cell types, in synergy with aging and ischemic lesions of the vessels. “Vascular dementia being an aging disease, this double observation – a decreased regulation linked both to disease and to aging – has highlighted a possibly important role. The CD39 generates, through several stages, the molecule of Adenosine, which links to A3AR, and modifies inflammation, by reducing some of its harmful effects “they describe. The Serpine2-LRP1 system has also been dysregulated in models of vascular dementia, and associated with tissue repair and cognitive recovery.
Repositioning a treatment against psoriasis
The team then tested a medication targeting this system in mice and being the subject of clinical trials in psoriasis, the Piclidenoson, an A3AR agonist. The researchers observed in mice that his administration favored the repair of the brain fabric and the recovery of memory and walking functions. “The most exciting discovery is that the late intervention still works”, Add the authors. Based on these promising results, researchers wish to conduct other studies before they can start trials in humans. The team is optimizing the dosage and exploring biomarkers to follow the efficiency of therapy.
