LA JOLLA, Calif. — Scientists have discovered a potential medical breakthrough in the treatment of multiple sclerosis. Researchers from Sanford Burnham Prebys unveiled a remarkable molecular connection between vitamin B12 and MS, occurring within astrocytes, non-neuronal glial cells in the brain.
For years, scientists have noticed a curious resemblance between vitamin B12 deficiency, a critical nutrient vital for the central nervous system (CNS), and MS, a chronic condition where the immune system mistakenly attacks the CNS, leading to neurodegeneration. Both conditions share similar neurological symptoms, such as numbness, vision problems, difficulty walking, and cognitive issues like memory troubles.
Researchers are now proposing new avenues for enhancing MS treatment through CNS-B12 supplementation.
“The shared molecular binding of the brain’s vitamin B12 carrier protein, known as transcobalamin 2 or TCN2, with the FDA-approved MS drug fingolimod provides a mechanistic link between B12 signaling and MS, towards reducing neuroinflammation and possibly neurodegeneration,” says Dr. Jerold Chun, professor and senior vice president of neuroscience drug discovery at Sanford Burnham Prebys, in a media release. “Augmenting brain B12 with fingolimod or potentially related molecules could enhance both current and future MS therapies.”
Essentially, their research suggests that by boosting vitamin B12 in the brain using drugs like fingolimod, it might be possible to improve the treatment of MS.
The study focused on the molecular workings of fingolimod (Gilenya®), an FDA-approved medication for MS. Fingolimod is a sphingosine 1-phosphate (S1P) receptor modulator that suppresses the abnormal activity of immune cells (T and B cells) that attack the brains of MS patients.
Using animal models of MS and examining human post-mortem brain tissue, researchers found that fingolimod reduces neuroinflammation by regulating the pathways involved in B12 communication. Specifically, it increases the levels of a B12 receptor called CD320, which is crucial for taking up and using B12 bound to TCN2. TCN2 is responsible for distributing B12 throughout the body, including the CNS. This interaction with fingolimod was newly discovered within astrocytes, non-neuronal cells in the brain. Importantly, this relationship was also observed in human MS brains.
Researchers highlighted a significant finding: lower levels of CD320 or a diet deficient in B12 worsened the course of MS in animal models and reduced the effectiveness of fingolimod. This happened because fingolimod “hitched a ride” by binding to the TCN2-B12 complex, facilitating their delivery to astrocytes through interactions with CD320. Disruptions in this process exacerbated the disease.
These findings underscore the potential benefits of B12 supplementation, especially when it comes to delivering B12 to astrocytes in the brain. Moreover, the study suggests that other S1P receptor modulators on the market, like Mayzent®, Zeposia®, and Ponvory®, might also influence this CNS mechanism. This opens the door to enhancing drug efficacy for this class of medicines by combining them with B12 supplementation.
The study also offers new insights into how the B12-TCN2-CD320 pathway is influenced by sphingolipids, particularly sphingosine, which is similar to fingolimod. This could pave the way for improved MS therapies and potentially benefit other neuroinflammatory and neurodegenerative conditions in the future.
“It supports creating brain-targeted B12 formulations,” says Dr. Chun. “In the future, this mechanism might also extend to novel treatments of other neuroinflammatory and neurodegenerative conditions.”
The study is published in the journal Cell Reports.
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