In a new study<\/a> researchers\u00a0 have identified 10 compounds that are able to reduce PrPSc<\/sup> levels in infected cells and have shown that the most potent molecules can also prevent the toxicity that was observed when applying PrPSc<\/sup> to cultured neurons.<\/p>\n The researchers had initially explored the anti-prion properties of these molecules because they were known to bind to the sigma receptors (\u03c31<\/sub>R and \u03c32<\/sub>R), which they had reason to believe were involved in prion proliferation. Using gene knockout technology (CRISPR), they determined that the sigma receptors were not the relevant targets of these drugs, from the perspective of their anti-prion properties.<\/p>\n Using Neuro2a cells (N2a) from an experimental model that had been infected with prions, these cells were then exposed to increasing concentrations of each drug, and the levels of PrPSc<\/sup> were determined. They then used CRISPR technology to \u201cedit\u201d the \u03c31<\/sub>R and \u03c32<\/sub>R genes, such that they no longer coded for a protein, and found this had no effect upon the decrease in PrPSc<\/sup> levels they observed when applying the drugs. This led them to conclude that \u03c31<\/sub>R and \u03c32<\/sub>R were not responsible for the anti-prion effects of these drugs. They then went on to test the ability of these drugs to inhibit the PrPC<\/sup> to PrPSc<\/sup> conversion and found they had no effect on these cell-free reactions, indicating that another protein mediates the effects of these drugs.<\/p>\n![\"Headshot](\"\/camed\/files\/2024\/05\/mercer_robert-e1715790733697.jpg\")
\u201c<\/em>Excitingly, five of these molecules have a history of use in humans: rimcazole and haloperidol for neuropsychiatric conditions, (+)-pentazocine for neuropathic pain, and SA 4503 and ANAVEX2-73, which are in clinical trials for ischemic stroke and Alzheimer\u2019s disease, respectively,\u201d explained lead author Robert C.C. Mercer, PhD<\/a>, an instructor of biochemistry and cell biology at the school.<\/p>\n![\"Head](\"\/camed\/files\/2015\/06\/David-Harris-1.jpg\")
According to the researchers, prion diseases have enormous public health implications from the safety of the blood supply to the proper decontamination of surgical tools used in neurosurgery. \u201cFrom a clinical standpoint, we believe this research has uncovered anti-prion properties of drugs that have already been shown to be safe to use in humans. Because of this, especially considering the absence of any effective treatment for these diseases, these compounds could be re-purposed for treatment of prion diseases,\u201d said corresponding author David A. Harris<\/a>, MD, PhD, the Edgar Minas Housepian professor and chair of biochemistry & cell biology at the school.<\/p>\n