By: M. Wessling
A recently published study by Wen et al  provides an encouraging look at a possible therapy for the chronic neuro-inflammatory disease multiple sclerosis (MS). What is even more interesting is that this experimental autoimmune encephalitis myelitis (EAE) study, which used the List Labs Product #180 Pertussis Toxin in mice to induce autoimmune symptoms, supports observations that MS patients and their physicians have accumulated for decades—the relationship between sunlight and MS progression. It also supported a 2015 study by Thouvenot et al  that showed a relationship between the degree of disability in fully ambulatory patients with the relapsing-remitting form of MS and Vitamin D deficiency, related in some cases to insufficient exposure to sunlight.
Challenges associated with MS treatments
Introducing and developing new effective treatments for MS is challenging because the disease has different levels and rates of progression in different patients. In fact, there is evidence that 25% to 50% of persons with MS choose not to take existing disease-modifying therapies, even though the risks and benefits are well known. MS is also approximately 1.5 times more prevalent in women than men, and more frequent in more northerly regions, and MS is now being recognized more frequently in children than before. Indeed, the prevalence of MS is prone to uncertainty; mostly since MRI, which is used to diagnose MS is not available in poorer regions. Another confounding factor is that in some traditions there may be a perceived cultural association between the symptoms at onset—fatigue, blurring of vision, motion impairments—and moral culpability.
Scientific research for MS treatments is progressing
However, recent years have brought much progress in the analytical scientific methods that show changes in cell structure in in vivo samples from patients with MS. Oxidative stress was identified as a major factor in the cell apoptosis that leads to neurodegenerative diseases, such as MS. The study by EM Kuklina  used blood samples from MS patients to conclude that melatonin plays a definitive role as an effective regulator of immune reactions that act through the subset of T lymphocytes producing IL-17 (Th17). As the Th17 subset plays a key role in MS pathogenesis, the results suggest that melatonin could nullify the immunomodulating hormone effects toward Th17.
The Wen EAE study bridges the gaps between scientific theory and human observation using genetically characterized mice under carefully controlled conditions. This study therefore could lead to new and effective therapies for MS. Going beyond previously published studies on the effects of melatonin, these authors examined the effects of treatment with melatonin and its precursor, N-Acetylserotonin (NAS), on neurodegenerative symptoms that parallel those in human MS. The EAE results showed clinical improvement that included reduced inflammatory markers and free radical generation, and sparing of axons, oligodendrocytes, and myelin. Further, the proposed mechanism would explain how the decline in motor symptoms in the NAS and melatonin-treated mice is linked to the role of Th1 cytokines in MS progression.
While it’s very different from our Pertussis Toxin, another List Labs product used in Multiple Sclerosis research is Epsilon Toxin (Product #126A). Read about it here: Epsilon Toxin: A Fascinating Pore Forming Toxin That Crosses The Blood Brain Barrier
See other uses of List Labs products in recent research on our Citations page, featuring thousands of articles with abstracts.
- Wen J, Ariyannur PS, Ribeiro R, Tanaka M, Moffett JR, Kirmani BF, Namboodiri M, Zhang Y. Efficacy of N-Acetylserotonin and Melatonin in the EAE Model of Multiple Sclerosis. J Neuroimmune Pharmacol 2016 Aug. 25 [Epub ahead of print]. PMID: 27562847
- Thouvenot E, Orsini M, Daures J-P, Camu W. Vitamin D Is Associated with Degree of Disability in Patients with Fully Ambulatory Relapsing-Remitting Multiple Sclerosis. Eur J Neurol 2015, 22: 564-569. PMID: 25530281
- National Multiple Sclerosis Society. Multiple Sclerosis FAQ’s. New Research Fall 2015. Acquired 10/30/2016.
- Alonso A, Hernán MA. Temporal Trends in the Incidence of Multiple Sclerosis: A Systematic Review. Neurology 2008; 71:129-135. 2008. PMID: 18606967
- Kuklina EM. [Melatonin as an Inducing Factor for Multiple Sclerosis.] Zn Nevrol Psikhiatr Im S S Korsaakova. 116 (5):102-5. 2016. [Article in Russian]
By: Md. Elias Ph.D, Senior Scientist
Epsilon Toxin Linked to Multiple Sclerosis
List Labs recently added Product #126A, pure Native C. perfringens Epsilon Toxin to its product line. Although Epsilon Toxin related pathology and disease are common in farm animals and rare in humans, recent studies suggest potential involvement of this toxin with Human Multiple Sclerosis (MS), an inflammatory disease of the CNS currently affecting 2.5 million people worldwide with diverse neurological symptoms such as autonomic, motor, and sensory problems.
Epsilon Toxin used in Cell Signaling
Aside from this toxin’s pathologic significance to understand and treat MS, it can be used as valuable reagent and tool in the field of cell signaling. Unlike other inhibitory neurotoxins, Epsilon Toxin can be used to stimulate dopamine and glutametargic neurons. The toxin has been shown to be sensitive to MDCK cells and bind to the brain endothelial cells. Epsilon Toxin has been reported to be used as delivery vehicle to facilitate the transport of drugs through the blood brain barrier for the treatment of experimental malignant brain tumors in mice. Epsilon toxin is also classified as a category B bio-threat agent by the CDC due to its potent toxicity and potential for malice and the purified epsilon toxin will be a valuable reagent in vaccine development and bio-defense research.
Epsilon Toxin is controlled by the US Department of Commerce and an export license is required for international shipments. However, it is not one of the Select Agents & Toxins regulated by the CDC and the USDA.