by Scientists have long observed a striking similarity between vitamin B12 deficiency and multiple sclerosis (MS) in terms of their neurological symptoms. Both conditions can cause numbness or tingling in the extremities, vision loss, difficulty walking or speaking, and cognitive dysfunction. In a recent study published in Cell Reports, researchers from Sanford Burnham Prebys, along with collaborators from other institutions, have uncovered a molecular connection between vitamin B12 and MS that occurs in astrocytes, non-neuronal glial cells in the brain.
The study, led by senior author Jerold Chun, MD, PhD, and co-corresponding author Yasuyuki Kihara, PhD, suggests that improving the treatment of MS may involve supplementing the central nervous system (CNS) with vitamin B12. The researchers found that there is a shared molecular binding between the brain’s vitamin B12 carrier protein, known as transcobalamin 2 or TCN2, and the FDA-approved MS drug fingolimod. This connection provides a mechanistic link between B12 signaling and MS, potentially reducing neuroinflammation and neurodegeneration in MS patients.
The team focused on fingolimod, a drug that suppresses the distribution of T and B immune cells that attack the brains of MS patients. They discovered that fingolimod suppresses neuroinflammation by regulating B12 communication pathways and increasing the levels of a B12 receptor called CD320. CD320 is necessary for the uptake and utilization of B12 when it is bound to TCN2, which distributes B12 throughout the body, including the CNS. This interaction between fingolimod and the B12 pathway was observed in both animal models of MS and human post-mortem brains, highlighting its relevance to the disease.
The researchers also found that lower levels of CD320 or dietary B12 restriction worsened the disease progression in the animal model of MS. Additionally, these factors reduced the therapeutic effectiveness of fingolimod. Fingolimod is able to bind to the TCN2-B12 complex, allowing it to be delivered to astrocytes via interactions with CD320. Disruptions in this process can aggravate the disease.
These findings suggest that supplementing B12, especially targeting its delivery to astrocytes in the brain, could be beneficial for MS patients. The researchers speculate that other S1P receptor modulators on the market, such as Mayzent, Zeposia, and Ponvory, may also impact the B12-TCN2-CD320 pathway. The study supports the idea of combining B12 supplementation with these drugs to enhance their efficacy in treating MS.
Furthermore, the study highlights the potential for regulating the B12-TCN2-CD320 pathway through sphingolipids, particularly sphingosine. Sphingosine shares structural similarities with fingolimod and could play a role in improving future therapies for MS and other neuroinflammatory and neurodegenerative conditions.
These findings provide valuable insights into the molecular mechanisms underlying MS and suggest new avenues for treatment. By targeting the B12-TCN2-CD320 pathway, researchers may be able to develop more effective therapies for MS and potentially other related neurological disorders.
