Glutamate is the most prominent neurotransmitter that is released in the brain by nerve cells. At the right concentrations and locations, glutamate is necessary for proper brain functionality. Elevated glutamate levels are associated with diseases like Alzheimer's and Multiple Sclerosis. When there are increased levels of glutamate in a cell, it becomes overexcited leading to damage and degeneration. This neurotransmitter has many important functions in the body involving learning & memory, chemical messaging, and pain signaling. It is also responsible for making gamma-aminobutyric acid which aids with muscle function and more. Glutamate is referred to as excitotoxin when nerve cells are overexcited. In MS, tissue destruction is caused by the immune system launching an attack on the brain and spinal cord. However, researchers have linked the excitotoxicity of nerve cells to tissue degeneration in MS.
Myelin serves as a protection barrier around the brain and spinal cord. In Multiple Sclerosis, immune cells will attack the myelin and the cells that create myelin. When this protective layer is damaged, signals have a difficult time being relayed or can't be relayed at all. In addition, inflammation is triggered in the immune system as a response. This is why all prior treatments for MS have been immunomodulatory drug treatments for RRMS, directed at treating the immune reactions causing demyelination. Recently, a group of scientists have explored the idea that demyelination occurs prior to an immune response. Dr. Fang Liu and her team at CAMH had a new approach to developing a drug for MS by focusing on targeting the glutamate system instead. The team at CAMH led a pre clinical drug trial using a small molecule that prevents excitotoxicity through an allosteric binding site. This miniscule lead compound was found effective in two different mouse MS models, blocking excitotoxicity. These mouse models served as an imitation of the immune system and damaged tissue in a human MS case. The molecule was found to reduce MS symptoms and reverse damage to myelin, while also maintaining neurological functions and signaling. This treatment can prove incredibly beneficial as an alternative treatment to MS or to work alongside a pre-existing treatment. Dr. Liu compared this probable treatment to chemotherapy as “simultaneous targeting of the MS disease pathway at multiple points can have synergistic effects and result in better outcomes.” The funding for this decade-long study was provided by the National Multiple Sclerosis Society Fast Forwards Research Program and MS Canada.
This promising trial has opened a new window into treatments targeting the glutamate system rather than the immune system in Multiple Sclerosis. This potential drug uses neuroprotection to combat myelin death and MS symptoms by focusing on the preservation of neurons. Further testing needs to be done before human trials can proceed. However, Dr. Ian Greig is working to remodel Dr. Liu’s molecules into drugs to be used in a clinical trial for patients. In addition, a patent application has been filed by The University of Aberdeen and CAMH to protect this study and progress it to the next stage in a couple of years.
References
CAMH. (2023, December 8). CAMH develops potential new drug treatment for multiple sclerosis. CAMH. Retrieved January 19, 2024, from https://www.camh.ca/en/camh-news-and-stories/camh-develops-potential-new-drug-treatment-for-multiple-sclerosis
. . - definition of . . by The Free Dictionary. (n.d.). The Free Dictionary. Retrieved January 19, 2024, from https://www.science.org/doi/10.1126/sciadv.adj6187
National MS Society. (2023, December 8). Positive results from mouse studies testing a new experimental therapy for MS. National MS Society. Retrieved January 19, 2024, from https://www.nationalmssociety.org/About-the-Society/News/Positive-results-from-mouse-studies-testing-a-new
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