Nature: Study finds new ways to treat certain neurological disorders

, July 3, 2020 /

BIOON/ -- A team led by medical researchers at Case Western Reserve University has developed a potential treatment for Perizois-metzbach disease (PMD)It is a deadly neurological disease caused by a genetic mutation that prevents the body from producing myelin, a protective insulator around nerve cellsusing mouse models, the researchers identified and validated a new therapeutic target -- a toxic protein caused by a genetic mutationNext, they successfully used a series of drugs called asos (antisense oligonucleotides), anantisense oligonucleotides, to stop the production of the ribonucleic acid (RNA) chain that produces abnormal proteinsThis treatment reduces the signature symptoms of PMD and extends life, establishing the clinical potential of this approachPhoto Source: Case Western Reserve University
By demonstrating the effective delivery of myelin cells in the nervous system by ASOs, the researchers point to the prospect of using this method to treat other myelin diseases caused by dysfunction of these cells, including multiple sclerosis (MS)Their study was published online July 1 in the journal Naturepreclinical results are profoundThe results of the study open the door to the development of the first treatment for PMD and new treatments for myelin disease, which typically results in models of PMD mice that typically die in a few weeks of birth and have a normal life span after treatmentPMD attacks young man'sPMD is a raregeneticdisease that affects the brain and spinal cord and mainly affects boysSymptoms can occur in early infancy and begin to move in the eye balls and abnormal head movementsOver time, children develop severe muscle weakness and stiffness, cognitive impairment
, difficulty walking, and inability to speak The disease shortens life expectancy and the most severely ill people die in childhood the disease is caused by a genetic error called proteoprotein 1 (protelipido protein 1, PLP1) Normally, this gene produces protein lipoprotein (PLP), the main component of myelin, which wraps and isolates nerve fibers, allowing electrical signals to travel properly through the nervous system But defects in the PLP1 gene produce toxic proteins that kill the cells that produce myelin and block the normal development and function of myelin, leading to severe neurological dysfunction in PMD patients PMD affects thousands of people around the world So far, there has been no treatment to reduce its symptoms or extend life for nearly a decade, Paul Tesar, a professor in the Department of Genetic
s and Genomics at the Faculty of Medicine, and his team have been working to better understand and develop new treatments for myelin disease They have achieved a number of successes, and their myelin regenerative drug for multiple sclerosis is now in the commercial development phase the latest study
In current laboratory work, researchers have found that the mutated PLP1 and its toxic proteins can restore myelin-producing cells, produce functional myelin, reduce disease symptoms and extend life after identifying PLP1 as their treatment target, the researchers made preclinical treatment choices They know that mutations in the PLP1 gene produce the wrong RNA strands, which in turn produce toxic PLP proteins , they partnered with Ionis Pharmaceuticals, a leader in RNA-targeted therapy and a pioneer in ASOs These chemically modified DNA short strands can be designed to bind to specific RNA targets and prevent the production of their protein products that's exactly what happened in their study The result is an improvement in myelin, improved motor ability, and a substantial increase in life expectancy "ASOs provide an opportunity to cut off pathogenic proteins from the source." Picture Source: Case Western Reserve University Successful clinical applications of ASOs are relatively new, but recent developments seem promising In 2016, the U.S Food and Drug Administration approved the first ASO drug to treat spinal muscular atrophy in the nervous system The drug, called Spinraza, was developed by Ionis and commercialized by Biogen Inc More ASO therapies are being developed and clinical trials , promising to address many neurological diseases, and there are no effective treatment options Tesar says ongoing and planned trials in his lab will help guide future clinical development of ASO treatments for PMD For example, the researchers wanted to learn more about how effective treatment works after symptoms appear, how long the effect lasts, how long it takes to treat, and whether it works for all PMD patients -- regardless of their specific course of disease Despite important research questions, Tesar is cautiously optimistic about the future of this approach to clinical development and trials in PMD patients, and he sincerely hopes that their work will make a difference for PMD patients and their families (BioValleyBioon.com) references: Research finds new approach to treating the science diseases
Elitt, M.S., Barbar, L., Shick, H.E et al.
Suppression of the proteolipid protein rescues Pelizaeus-Merzbacher disease Nature (2020) https://doi.org/10.1038/s41586-020-2494-3