Scientists have developed lower-cost therapy for uncommon genetic diseases

Scientists from an international research group suggested in Nature on Feb. 22 that blocking the molecules which cause Gauchers disease (GD) and other lysosomal storage disease (LSD) inflammation and organ damage can be used as a treatment, and this method is lower than the current treatment costs. More research through recombinant human proteins will be conducted.

Through the study of laboratory mouse models and human cells, the team showed that C5aR1 is a key molecular pathway in driving the inflammatory process of Goie disease. The process of inflammation of Geshe disease is initiated by the mutation of GBA1 gene. GBA1 encodes lysosomal enzyme glucocerebrosidase (GCase), which degrades the adipose molecule glucoamate (GC). C5aR1 is a small peptide (protein component) receptor from a complement system known as C5a (part of the immune system) that drives inflammation in several different types of immune cells.

Dr. Manoj Pandey, a scientist at the Syndicate Children's Human Genetics Division, and his colleagues showed that inflammatory glucose enamel accumulation in the spleen, liver, lung and bone marrow immune cells drives the self-expression of the glucose-ceramide that forms the immune complex antibody induction. These immune complexes promote the production of C5a and the activation of its receptor C5aR1.

Based on the evidence that C5aR1 participates in the process of Goie's disease, the researchers decided to test targeted molecular pharmacology in laboratory mouse models. Using C5aR antagonists (C5aRA) developed by K?hl, scientists injected C5aRA into the peritoneal cavity of mice. In the lung, liver and spleen of mice, the infiltration of proinflammatory immune cells (macrophages) is substantially reduced, and the accumulation of glucose-ceramide is almost completely eliminated.

Because the current project was carried out in mouse models and human blood cells, Pandey and his colleagues stressed the need for additional research before determining whether C5aR1 is effective and safe enough to be tested in human patients.

Pandey said the researchers will continue to test the C5aRA molecules used in mouse studies that are effective in targeting human and mouse C5aR. They will also test commercially available anti-C5 monoclonal antibodies called eculizumab and produced by Alexion Pharmaceuticals, which helped finance this study. This will allow researchers to test these compounds as a neoadjuvant therapy for human patients with Gaucher and other lysosomal storage diseases. Flarebio provides you with high-quality recombinant proteins such as recombinant Nrg2 at competitive prices.