Prevents tau hyperphosphorylation
MEDIFRON (KOSDAQ: 065650), headquartered in Seoul, a biotechnology company developing new diagnostics and therapeutics for Alzheimer’s disease (AD), announced on November 22nd that it had filed the international patent application under the PCT (Patent Cooperation Treaty) for ‘MDR-0214’, a novel candidate molecule for the treatment of AD.
The PCT is an international patent law treaty, which provides unified procedures for applications to protect patent rights in its member countries, enabling the near global patent coverage. However, a PCT application itself does not grant a patent and needs to be proceeded with the step of entering into national phase for the grant of patents.
O-GlcNAcylation, a form of glycosylation, regulates the phosphorylation of tau reciprocally. The decrease in O-GlcNAcylation as in AD brings about the increase in phosphorylation (called hyperphosphorylation) of tau. Two enzymes control this glycosylation of tau at the phosphorylation sites (serine and threonine): O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). OGT catalyzes the addition of O-GlcNAc (O-linked β-N-acetylglucosamine) to serine and threonine, whereas OGA cleaves O-GlcNAc from proteins, as in the case with kinases and phosphatases for phosphorylation of tau. Therefore, the facilitation of OGT/phosphatase or the inhibition of OGA/kinase gives rise to the decrease in phosphorylation of tau.
MEDIFRON has developed its novel therapeutic agent ‘MDR-0214’ that inhibits the actions of OGA, one of the enzymes that cause hyperphosphorylation of tau as explained above.
MDR-0214 was able to stem off the phosphorylation and aggregation of tau proteins by blocking the OGA, thereby improving the cognitive functions including memory, in the preclinical studies. The company had filed an application for the patent for MDR-0214 in South Korea last year.
“There have been evidences that the OGA inhibitors are directly related to the necroptosis of neurons, as well as to the phosphorylation of tau, signifying the potential to be used for the prevention and treatment of AD,” said MEDIFRON.
In March, 2020, MEDIFRON’s novel glutaminyl cyclase inhibitor ‘MDR-1703’, a candidate molecule for the treatment of AD, had been granted the patent in the South Korea. The glutaminyl cyclase catalyzes the formation of toxic pyroglutamate-modified beta-amyloid peptides (pyroGlu-Aβ). By suppressing the activity of glutaminyl cyclase, MDR-1703 reduces the amount of pyroGlu-Aβ.
The company, in collaboration with Chonnam National University, has been conducting researches in order to develop therapeutic molecules that target tau protein which is known as one of the main culprits of AD, along with beta-amyloids and neuroinflammation. Among outcomes are Aβ-aggregation inhibitor (MDR-1339), RAGE (Receptor for Advanced Glycation Endproducts) inhibitor (MDR-066), and NLRP3 (NLR Family Pyrin Domain Containing 3) inhibitor.
MEDIFRON, jointly with QuantaMatrix, also developed its proprietary diagnostic kit ‘QPLEX Alz plus assay’ to detect beta-amyloid in the blood for early prediction of AD even before the onset of dementia. The item permission for ‘QPLEX Alz plus assay’ was approved by the Ministry of Food and Drug Safety of South Korea in July 2020.