Science & Technology, UK (Commonwealth Union) – RBM3 is a protein that binds to RNA molecules and plays a role in various cellular processes, including RNA metabolism, translation, and stress response. It is also known as the “cold shock protein” because its expression is induced by cold temperature stress in cells.
Researchers have used a form of gene therapy to elevate the levels of RBM3 in the brains of mice, to protect them against the potentially devastating impact of prion disease.
Prion diseases, are a group of rare and fatal neurodegenerative disorders that affect humans and animals. They are caused by prions which are misfolded proteins accumulating in the brain and leading to damage in nerve cells, resulting in progressive neurological dysfunction.
The scientists of the study indicated that the findings are a step towards harnessing the defensive effects of brain cooling in the treatment of patients with acute brain injury and possibly block dementias, like Alzheimer’s disease.
As the body drops its temperature significantly, it elevates its levels of RBM3. These effects were 1st noticed in hibernating animals. There are assumptions that during hibernation, the protein assists in protecting the brain from destruction, permitting it to continue making new connections.
In 2015, Professor Giovanna Mallucci and colleagues demonstrated in mice that RBM3 can protect the brain against deterioration linked with build-up of misfolded proteins, which may result in various forms of dementia, like Alzheimer’s and Parkinson’s disease, and from prion diseases like Creutzfeldt-Jakob Disease (CJD).
Induced hypothermia is applied in the treatment of patients in intensive care units. these include newborn babies along with traumatic brain injury patients, where patients are put into a coma and their brains cooled to guard against deterioration. However, this may lead to other risks, like blood clotting and pneumonia. There was a question by researchers if the cold shock protein can be harnessed for the treatment of patients with no cooling of the body, giving a safer treatment for acute brain injury or a procedure for the protection of the brain against dementia.
The findings were published in EMBO Molecular Medicine, where researchers at the UK Dementia Research Institute, University of Cambridge, and the Institute of Chemistry as well as Biochemistry, Freie Universität Berlin, explored if a form of gene therapy known as antisense oligonucleotides (ASOs) may elevate the levels of the cold shock protein in mice brains and hence lead to their protection.
Researchers evaluated the gene that codes for the formation of the cold shock protein discovering that it contains a key element which in regular conditions blocks its expression. Removing, or ‘dialling down’ this element with the application of an ASO, leads to a long-lasting boost to production of RBM3.
In exploring if this approach may guard the brain, the scientists utilized mice infected with prions. Some of these mice received injections of a single dose of the ASO after 3 weeks, while the others were provided with a control treatment.
The scientists noted that 12 weeks after being administered the prions, the mice that had obtained the control treatment succumbed to prion disease demonstrating extensive loss of neurons in the hippocampus, which is the part of the brain vital for memory.
The results were much different for the mice that were given the ASO, the same time where the other mice were succumbing to the prion disease. The ASO-treated mice had levels of RBM3 which were double that of the other mice. The results had also indicated that 7 of the 8 ASO-treated mice demonstrated a wider preservation of neurons in the hippocampus.
The main funding for the study was received from the Freie Universität Berlin and by the UK Dementia Research Institute, which in turn is funded by the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK.
