Research Decoder: Remyelination versus Neuroprotection

hTwo words that I often see used interchangeably are remyelination and neuroprotection. Both processes are part of the body’s innate repair and damage prevention system, and they are critical tools for restoring function and integrity to damaged nerve cells and their protective coating in people with multiple sclerosis. However, remyelination and neuroprotection are distinct processes that lend themselves to different therapeutic approaches, and so knowing the difference between these terms is important in order to best capitalize on the diversity of molecular and cellular targets at our disposal for fighting MS.

Remyelination: Myelin makes up the protective coating around nerve fibres (axons) in our central and peripheral nervous systems in much the same way that insulation coats an electrical wire. Myelin helps to protect, support, and nourish the axon, and also increases the speed at which nerve impulses travel along the axon. During an MS attack, immune cells that infiltrate the central nervous system and produce inflammation cause damage to the myelin sheath; this exposes the axon to damage and slows down nerve conduction, resulting in the neurologic signs and symptoms of MS. Remyelination is a repair process by which myelin is reformed around the axons by specialized cells in the central nervous system called oligodendrocytes, thus helping to restore nerve conduction and protect the axon from further damage. In that sense, remyelination is one process that can help to promote neuroprotection.

Neuroprotection: This process encompasses a range of both innate molecular mechanisms and therapeutic approaches taken to protect axons and neurons from becoming injured and degenerating. While remyelination is one way of promoting neuroprotection, other methods can include preventing damage to the myelin-forming oligodendrocytes, suppressing the molecular mechanisms that can lead to nerve cell death (excitotoxicity is one such injurious mechanism that is the focus of research interest), and supplying the nerve cells with nourishing or protective molecules that keep them healthy such as growth factors, antioxidant molecules, etc. Neuroprotective strategies are especially important in cases where myelin can’t be rebuilt, and is a critical step in managing MS and slowing the transition to the progressive form of the disease.

While disease-modifying therapies that target inflammation are the mainstay of treatments for people living with MS, it’s becoming increasingly clear that therapeutic strategies that promote remyelination and neuroprotection will be the key to stemming disease progression and reversing disability.

On the remyelination front, one drug under study is an antibody called BIIB033, which targets and blocks a protein on the surface of oligodendrocytes called LINGO-1 that normally prevents oligodendrocytes from producing myelin. By switching off the activity of LINGO-1, this drug has the potential to enhance remyelination in people with MS. Phase I clinical trials have demonstrated that this drug is safe and well tolerated, and a phase II study is currently underway examining the effectiveness of combined therapy with BIIB033 and Avonex in people with relapsing-remitting MS.

The therapeutic potential of transplanting stem cells capable of forming new myelin sheaths has also been the focus of intensive study. While cell transplantation techniques for promoting remyelination have been fairly successful in animal studies, translating this strategy of cell replenishment to humans has been met with a number of setbacks, although an interesting turn has seen certain stem cell therapies (such as the recently announced MESCAMS trial) emerge as valuable tools for reducing inflammation and possibly contributing to repair of the central nervous system.

A number of drugs are also being studied for their neuroprotective properties. The MS-SMART clinical trial that is currently recruiting participants is evaluating a combined therapy with the drugs amiloride, ibudilast, and riluzole for their potential neuroprotective effects in individuals with secondary progressive MS. These drugs are currently used for treating other conditions and the investigation of their neuroprotective effects in treating progressive MS is an example of drug repurposing.

Laquinimod, in addition to its immune modifying effects, is a drug that is being investigated for its neuroprotective actions; specifically, some evidence shows that laquinimod increases important factors in the brain that support the growth and survival of nerve cells. A handful of phase II and phase III studies have demonstrated positive results with laquinimod in reducing disability progression and brain volume loss, placing laquinimod as a promising candidate for confronting the progressive phase of MS.

Dimethyl fumarate (Tecfidera), an oral medication approved for the treatment of relapsing-remitting MS, has recently come under investigation for its anti-oxidant properties that could serve a neuroprotective function in addition to its immune-regulating mechanism.  A recent study administered a combination of dimethyl fumarate and interferon-beta in mice with an MS-like disease and showed that the combined therapy resulted in greater protection of nervous tissue than either drug on its own. To date, one clinical trial (DEFINE trial) has demonstrated dimethyl fumarate’s efficacy in significantly reducing disability progression in addition to relapse rates , although it remains to be seen whether these effects are mediated through a neuroprotective mechanism.

These and other treatments in the pipeline represent the next frontier in repairing the damaging effects of MS on nerve cells and myelin and, ideally, preventing or minimizing this damage in the first place. 

Image credits: © Cornelius20 | – Brain Maze Photo

Updated: March 31, 2015

Categories Research

National vice-president, research, past MS researcher, and PhD in Cellular and Molecular Medicine from University of Ottawa. Leads the MS Society's research program to find the cure for MS and improve the quality of life for people affected by the disease.

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