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Reversing the Damage of Multiple Sclerosis

幸运8平台彩票March 03, 2016

Reversing the Damage of Multiple Sclerosis

A History of Frayed Nerves

Hope, optimism, and cure are words that seem to have no place in a conversation about multiple sclerosis (MS). A wildly unpredictable disease first documented by Jean-Martin Charcot, a professor at the University of Paris and father of modern neurology, in 1868, MS damages the sheathing known as myelin that protects the central nervous system. 1 The remaining scar tissue or plaque seen on the brain of MS victims is called sclerosis, which gives the disorder its name. Like frayed electrical wiring, the exposed nerves manifest a dizzying array of debilitating symptoms, from numbness, fatigue, and hearing and vision loss to vertigo, paralysis, and neurologic issues. Worldwide, there are some 2.5 million MS sufferers. In the U.S., alone, more than 200 Americans are diagnosed with the disease every week. 2 While that news certainly does not give rise to hope, optimism, or talk of a cure, what does are some remarkable results scientists have seen using new drugs to fight the root cause of MS itself.

Building on Success

Since Dr. Charcot’s initial efforts to treat MS some 150 years ago, scientists have focused on developing a host of therapies to slow the progression of the disease with mixed results. Even now, as geneticists are experimenting with tissue transplants to fight MS, researchers concede that they do not yet fully understand its origins. The fact is MS remains an incurable disease. 3 That, however, may be about to change.

Thanks to a major research breakthrough in 2011, neuroscientists Paul J. Tesar  at Case Western Reserve School of Medicine, and a colleague, Robert Miller, now at George Washington University’s School of Medicine and Health Sciences, successfully isolated and investigated oligodendrocyte progenitor cells (or OPCs for short) in a petri dish. 4 The main function of OPCs is to create the previously mentioned myelin sheath that protects the slender projections of nerve cells, called axons. Tesar’s and Miller’s  research made it possible—at least in theory—to test the impact of drugs already proven safe for use in humans on OPC stem cells in vitro幸运8平台彩票. Doing so would cut years off the drug trialing process and help expedite novel MS treatments that address the disease at its very core. The only problem was there were simply too many drug combinations and too many opportunities for human error to creep into the analysis without automated help.

Say Hello to Harmony

That help came in the form of PerkinElmer’s and outfitted with , a machine-learning option that recognized different cell populations and regions using a simple learn-by-example approach. As part of PerkinElmer’s proprietary , these systems not only allowed researchers to easily set up assays and automate high-content imaging experiments, they provided a fully automated solution that removed human bias and the risk of human error from the cellular image analysis algorithms. Researchers then turned that unbiased cellular information into usable quantitative data to optimize the process used by Tesar’s team to identify eventually two compounds, miconazole and clobesol, out of more than 700 that simulate OPC growth into myelin-producing cells in both mice and humans. 5 

After systematically administering the drugs in varying doses to lab mice with MS, both miconazole and clobesol promoted myelin-producing cells. “It was a striking reversal of disease severity in the mice,” Dr. Miller says. “The drugs we identified are able to enhance the regenerative capacity of stem cells in the adult nervous stem. This truly represents a paradigm shift in how we think about restoring function to multiple sclerosis patients.” 6

Dr. Tesar agrees. “To replace damaged cells, the scientific field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road,” he says. “We asked if we could find a faster and less invasive approach by using drugs to activate native nervous system stem cells and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself.” 7

A Potential Cure

幸运8平台彩票Dr. Tesar is quick to point out that much more research is required before MS patients will be allowed to use these drugs to treat their disease. Currently, both drugs are used as topical medications. Miconazole is an ingredient in a number of over-the counter antifungal products, including powders and cream to treat athlete’s foot. Clobetasol, meanwhile, is available by prescription only for skin disorders such as dermatitis. Neither drug was ever considered as an effective treatment to possibly reverse the effects of MS, Tesar says.

According to the Tesar lab, the newly discovered functions of miconazole and clobetasol to reduce significantly the severity of MS in mouse models is prompting researchers to investigate the optimized dosing, delivery method, and chemical structure of the drugs that will be required for human testing while mitigating any off-target side effects.

“However,” the researchers concluded, “the ability of miconazole and clobetasol to cross the blood-brain barrier raises the exciting possibility that these drugs, or modified derivatives, could potentially advance into clinical trials for the currently untreatable chronic progressive phase of MS.” 8

幸运8平台彩票Maybe there is a place for hope, optimism, and a potential cure for MS after all.

PerkinElmer instruments are for research use only.  Not for use in diagnostic procedures.

References

  1. Loren A. Rolak, “”, National Multiple Sclerosis Society, 2009, accessed on January 4, 2016.
  2. National Multiple Sclerosis Society, “”, accessed on January 4, 2016. See also, Ann Pietrangelo and Valencia Higuera, “”, Healthline, March 24, 2015, accessed on January 4, 2016.
  3. David Gruenewald, Nancy Clayton Reitman, and Maura Del Bene, “”,  National Multiple Sclerosis Society Clinical Bulletin, 2012, accessed January 4, 2016. See also, Neuroscience staff, “”, Neuroscience.com, April 20, 2015, accessed January 4, 2016.
  4. Robert Miller and Paul Tesar, “”, Nature Bilotechnology, October 13, 2011, accessed on January 5, 2016.
  5. Fadi J. Najm, Mayur Madhavan, et. al, “Drug-Based Modulation Of Endogenous Stem Cells Promotes Functional Remyelination In Vivo,” Nature, June 11, 2015, Vol. 522, Issue 7555, pp. 216 – 220.
  6. Lisa Anderson, “”, George Washington University School of Medicine and Health Sciences, News Release, April 11, 2015, accessed on January 5, 2016.
  7. Neuroscience staff, “”, Neuroscience.com, April 20, 2015, accessed January 4, 2016.
  8. Fadi J. Najm, Mayur Madhavan, et. al, “Drug-Based Modulation Of Endogenous Stem Cells Promotes Functional Remyelination In Vivo,” Nature, June 11, 2015, Vol. 522, Issue 7555, pp. 216 – 220.

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