Therapeutic Manipulation of N-glycan Branching: Promise in the Fight against MS?

Multiple Sclerosis is characterized by inflammatory demyelination and degeneration of the nervous system.

Multiple Sclerosis (MS) is a horrible, debilitating disease that affects an estimated 3 million people world wide. My friend “Liz” is one of those 3 million. When I first met Liz, she was a bright bubbly young woman who loved crafts and entertaining. She had a huge room in her basement filled with rubber stamps, paper and other craft supplies. The first Christmas I knew her, she and her husband had four Christmas trees in their house. Liz decorated each tree with a different theme. Then abruptly she stopped appearing at the social functions she never missed. A year or so later came the news that she had been diagnosed with Multiple Sclerosis. The effects of the disease left Liz unsteady on her feet. She didn’t feel comfortable going to places she wasn’t familiar with. She could no longer drive. At times she could barely see, perhaps one of the cruelest blows to someone who so loved to create things.

Prior to learning of Liz’s diagnosis, my closest connection with MS was the main (fictional) character on a favorite TV show, which is to say I didn’t know much at all about the disease. I knew that it was a disease that affected the nervous system and not much else. As I watched Liz cope with the varying symptoms of MS with her usual bubbly enthusiasm seemingly undaunted, I found myself noticing papers and blogs that talked about MS, and I began to learn more about the disease itself.

Briefly, MS is characterized by inflammatory demyelination and degeneration of the nervous system. The disease gets its name from the scar tissue, or sclerosis, that develops in the brain and/or spinal cord following demyelination. Once the myelin around the nerves has been damaged or destroyed, the electrical signals they carry from the brain and spinal cord to the rest of the body are disrupted, effectively cutting off communication between the brain and parts of the body.

MS can manifest itself in a lot of different ways including:

  • Fatigue
  • Numbness
  • Walking (Gait), Balance and Coordination Problems
  • Bladder Dysfunction
  • Bowel Dysfunction
  • Vision Problems
  • Dizziness and Vertigo
  • Sexual Dysfunction
  • Pain
  • Cognitive Dysfunction
  • Emotional Changes
  • Depression
  • Spasticity

Any of these symptoms would make daily life a challenge, suffering several at once must make keeping a positive outlook a struggle.

Fortunately, there is a significant amount of research being done on MS. A PubMed search for Multiple Sclerosis and the publication date of 2011 returned 3003 results. Among all these papers is one that I recently read describing the positive results (in mice) of oral doses of the sugar N-acetylglucosamine (GlcNAc) (1). This particular paper had caught my eye because it was talking about something I recognized; I take glucosamine supplements to help my knees from getting sore when I am doing a lot of running.

Citing a study that linked mutations in a gene controlling an enzyme in the Asn (N)-linked protein glycosylation pathway to the regulation of T cell hyper activity, spontaneous inflammatory demyelination and neurodegeneration, as well as genome-wide sequencing results that link it to MS severity, the authors targeted N-glycan branching because it directly controls neuronal survival independent of inflammation. Several studies have offered strong evidence for N-glycan branching in demyelination and disease progress, and the authors hypothesized that disrupted N-glycan branching promotes both autoimmune demyelination and neurodegeneration in MS. They further speculated that manipulating the N-glycan branching by supplementing with the simple sugar GlcNAc could be a useful strategy in treating MS by correcting the molecular defect associated with the underlying cause of MS.

The results of this study found that oral doses of GlcNAc enhanced N-glycosylation and suppressed inflammatory T cell responses for a “MS-like” disease in mice, myelin oligodendrocyte glycoprotein (MOG)-induced Experimental Autoimmune Encephalomyelitis (EAE).

Although the authors point out that GlcNAc is readily available over the counter, a closer look showed that the supplements I take are Glucosamine HCl not GlcNAc . I also had to resist the urge to pick up the phone and call Liz and tell her she should talk to her doctor about these supplements. Why? Because this was one study, it was done in mice, and it is just the beginning of a path that might lead to a promising treatment for MS. Still, it is a glimmer of hope for everyone who suffers the affects of MS as well as for all of us who know someone like my friend Liz.

Reference

  1. Grigorian, A. et al. (2011) N-Acetylglucosamine Inhibits T-Helper 1 (TH1)/T-Helper 17 (TH17) Responses and Treats Experimental Autoimmune Encephalomyelitis.  J. Biol. Chem.  Sep 29. [Epub ahead of print].
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Kelly Grooms

Scientific Communications Specialist at Promega Corporation
Kelly earned her B.S. in Genetics from Iowa State University in Ames, IA. Prior to coming to Promega, she worked for biotech companies in San Diego and Madison. Kelly lives just outside Madison with her husband, son and daughter. Kelly collects hobbies including jewelry artistry, reading, writing, photography and knitting. She would like to be an avid runner, as evidenced by her growing collection of running gear and her single half-marathon finishers t-shirt.

2 thoughts on “Therapeutic Manipulation of N-glycan Branching: Promise in the Fight against MS?

  1. Thanks for the article! I’ve participated in and lead teams in the MS 150 Bike Ride for the past 4 years. The first year I participated, I knew nothing about MS and did it strictly for the challenge. When I crossed the finish line that first year, I had the opportunity to meet those diagnosed with this debilitating disease. When they showed me how grateful they were for participating in the event, told stories of their daily struggles, and heard the testament of those losing loved ones to MS, it changed my life forever. Now I make the 150 mile bike ride every year, recruiting team members to help raise money to fund research for a cure. Thanks for helping spread the word!

  2. Hi Jake. Wow, thanks for sharing your experience with the MS bike ride, and for recruiting a team to do the ride with you. I wish that more people could meet someone like those you met or my friend, the more times the stories are told the better! Thanks for raising money for MS research!! Keep pedaling. Kelly

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