The correlation between vitamin B12 deficiency and multiple sclerosis

Study results identify molecular signaling pathways that have the potential to enhance current MS treatments.

Scientists have noted interesting similarities between vitamin B deficiency and B vitamins for decades.₁₂ – Essential nutrients that support the healthy development and function of the central nervous system (CNS) – and Multiple Sclerosis (MS) is a chronic disease in which the body’s immune system attacks the CNS, causing neurodegeneration.

Both are vitamin B₁₂ (also known as cobalamin) deficiency and multiple sclerosis cause similar neurological symptoms, including numbness or tingling in the hands and feet, loss of vision, difficulty walking or talking normally, and cognitive impairment such as memory loss .

New research reveals molecular connections

In a new study published online on December 8, 2023, cell reportSanford Burnham Prebys researchers are working with other collaborators to describe a new molecular relationship between B vitamins.₁₂ The other is MS, which occurs in astrocytes, which are important non-neuroglial cells in the brain.

The findings of the study’s senior authors Jerrold Chun, MD, PhD, professor and senior vice president for neuroscience drug discovery, and Yasuyuki Kihara, PhD, associate research professor and co-corresponding author, and their colleagues, open new ways to conduct research. It suggests. Improving MS treatment through CNS-B₁₂ Replenishment.

“Covalent molecular bonds of vitamin B in the brain”₁₂ A carrier protein known as transcobalamin 2 or TCN2 and the FDA-approved MS drug fingolimod provide a mechanistic link between B and B.₁₂ “Signal transduction and MS lead to reduced neuroinflammation and possibly neurodegeneration,” Chun said.

“Strengthen Brain B”₁₂ When used in combination with fingolimod or potentially related molecules, it could potentially enhance both current and future MS treatments. ”

Study details and impact

In their paper, the Sanford Burnham Prebys team, along with collaborators from the University of Southern California, Japan’s Juntendo University, Tokyo University of Pharmacy, and the State University of New York, focused on the molecular function of FTY720, or fingolimod (Gilenya®). . ), a sphingosine 1-phosphate (S1P) receptor modulator that suppresses the distribution of T and B immune cells that mistakenly attack the brains of MS patients.

Using animal models of MS and postmortem human brains, researchers found that fingolimod suppresses neuroinflammation by functionally and physically modulating group B.₁₂ Enhance communication channels, especially B₁₂ A receptor called CD320 must take up and use the necessary B₁₂ If bound to TCN2 distributing B₁₂ throughout the body, including the CNS. This known process was newly identified through interaction with fingolimod within astrocytes. Importantly, this relationship was also observed in human MS brains.

Of particular note, the researchers reported lower levels of CD320 or dietary B;₁₂ The restriction worsened the disease course and reduced the therapeutic efficacy of fingolimod in animal models of MS.This occurred through a hitchhiking mechanism in which fingolimod binds to TCN2-B.₁₂ This complex allows delivery to all astrocytes via interaction with CD320, and loss of the component disrupts the process and exacerbates the disease.

These new findings further support the use of B .₁₂ It turns out that supplements, particularly fingolimod, can correct astrocyte B disorders in terms of delivering vitamins to astrocytes in the brain.₁₂ Pathways for MS patients.

Scientists say other commercially available S1P receptor modulators, such as Mayzent®, Zeposia® and Ponvory®, may be able to access at least part of this CNS mechanism.This study supports B₁₂ Supplementation with S1P receptor modulators aimed at improving the efficacy of this class of drugs.

This study also opens new avenues for how B functions.₁₂The -TCN2-CD320 pathway is regulated by sphingolipids, specifically sphingosine, an endogenous structural analog of naturally occurring fingolimod, for future improvements in MS treatment, Chun said.

“We support the creation of B that targets the brain.”₁₂ formulation. In the future, this mechanism may be extended to new treatments for other neuroinflammatory and neurodegenerative diseases. ”

Reference: “FTY720 requires astrocyte vitamin B12-TCN2-CD320 signaling to reduce disease in animal models of multiple sclerosis” (Deepa Jonnalagadda, Yasuyuki Kihara, Aran Groves, Manisha Ray, Arjun Saha, Clayton Ellington, Hyeon-Cheol Lee-Okada), Tomomi Furuhata, Takehiko Yokomizo, Edward V. Quadros, Richard Rivera, Jerrold Chun, December 7, 2023. cell report.
DOI: 10.1016/j.celrep.2023.113545

Additional authors of the study include Sanford Burnham Prebys, Alan Groves, Sanford Burnham Prebys, Deepa Johnnalagadda, Manisha Ray, Clayton Ellington, and Richard Rivera of the University of California, San Diego . Arjun Saha, University of Southern California. Juntendo University, Hyeon-Cheol Lee-Okada and Takehiko Yokomizo. Tomomi Furuhata (Tokyo University of Pharmacy) Edward V. Quadros, Downtown Medical Center, New York.

This research was supported by a grant from the National Institute of Neurological Disorders and Stroke. National Institutes of Health (R01NS103940), Novartis, Ministry of Education, Culture, Sports, Science and Technology/JSPS KAKENHI (18H02627, 19KK0199, 21H04798, 18K16246 and 21K08565). Additional support was provided by the Uehara Memorial Foundation, Kanae Medical Foundation, Mochida Memorial Medical and Pharmaceutical Research Foundation, Human Frontier Science Program, and the University of California, San Diego Medical Scientist Training Program and Pharmacology Training Grant (T32GM007752). . ).