Background
In people living with multiple sclerosis, the lesions in the brain that result from damage to myelin can arise from different processes. The “outside-in” process reflects the attack of myelin from inflammation-producing cells that enter the central nervous system from outside and cause damage. The “inside-out” process, on the other hand, results from changes that take place inside the central nervous system, that then cause the surrounding myelin-producing cells to become seriously damaged. In either case, destruction of nerve tissue and myelin-producing cells (called oligodendrocytes) can lead to significant tissue injury, an array of symptoms and irreversible disability in MS.
Since the production of myelin by oligodendrocytes requires a great deal of energy, scientists believe that problems with how nerve fibres generate and metabolize energy may be one culprit for the “inside-out” process of lesion formation. Researchers at McGill University are studying a promising neuroprotective approach to preventing damage to nerve fibres and promoting remyelination of injured fibres by looking at this energy metabolism process closer. Drs. Tim Kennedy and Jack Antel as well as MS Society-funded doctoral candidate Diane Nakamura recently published a study funded by the MS Society in which they observed the behaviour of cells to determine if an experimental compound called RNS60 could both maintain existing myelin and promote repair. The study was published in the journal Scientific Reports.
The Study
To examine the therapeutic potential of RNS60, the researchers collected underdeveloped oligodendrocytes (called oligodendrocyte precursor cells - OPCs) from rats and encouraged their maturation into oligodendrocytes. They then deprived the cells of glucose and other nutrients to mimic the “inside-out” process of tissue injury that is seen in many MS lesions.
The cells were divided into two groups: one group was treated with the RNS60 compound, while the other was left untreated and served as a control for comparison. To determine the effects of RNS60, the researchers measured factors like energy metabolism, cell injury, maturation of OPCs and survival of oligodendrocytes, which they used as indicators of successful myelin maintenance and repair.
Results
The researchers found that when the glucose-deprived oligodendrocytes were treated with RNS60, they showed less evidence of injury compared to untreated controls. Energy metabolism was improved in the presence of RNS60, which was a positive finding since proper maintenance of myelin is known to consume large amounts of metabolic energy.
Importantly, the researchers found that survival of glucose-deprived oligodendrocytes was higher when treated with RNS60. This was accompanied by improved maturation of OPCs, which reflects a greater ability of these cells to promote remyelination of MS lesions and maintain healthy levels of myelin.
Comment
The study demonstrates that the experimental compound RNS60 is a promising therapeutic candidate for protecting nerve fibres and promoting remyelination of damaged ones in MS lesions that have been formed from the “inside-out”. By protecting myelin-producing cells from succumbing to the damaging effects of metabolic stress, RNS60 offers a potential future alternative to currently approved disease modifying therapies for MS, which work by influencing the immune system and preventing damaging inflammation from the “outside-in”.
RNS60 is still at a very early stage of research and the next step for the researchers will be to study the compound thoroughly in animals with an MS-like disease before it can progress through the drug development process into clinical studies. The compound accompanies a new, growing class of experimental therapies that are use neuroprotective and remyelinating approaches to treating the disease. This includes drug candidates that are even further along the drug development process, such as those being developed by MS Society-funded researchers Drs. Veronique Miron and David Granville with the help of experts at the Centre for Drug Research and Development (CDRD). Continued research in the areas of neuroprotection and remyelination brings about an improved outlook for developing new treatments for progressive forms of MS, for which existing disease-modifying therapies are relatively ineffective.
Source
Rao VT et al. Potential Benefit of the Charge-Stabilized Nanostructure Saline RNS60 for Myelin Maintenance and Repair. Sci Rep. 2016;6:30020.