TAU discovers better model to find MS cure

Scientists use mice with type 1 diabetes that actually develop MS; breakthrough could lead to better treatments.

By JUDY SIEGEL-ITZKOVICH
Mouse 311 (photo credit: Courtesy of American Friends of TAU)
Mouse 311
(photo credit: Courtesy of American Friends of TAU)
All laboratory research on multiple sclerosis have been conducted until now using experimental autoimmune encephalomyelitis (EAE) as mouse model, even though it is not the same as MS. Mice with EAE – a scientific model first created in the 1920s – are raised by injecting the rodents with protein from myelin – the insulating material on the nerves that breaks down and in humans causes the disease. The myelin is then mixed with bacteria.
The mouse’s immune system attacks the myelin and produces an autoimmune-like response, which causes the disease in humans, but as bacteria are not involved in the debilitating neurological disease MS, it is not the same mechanism.
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But now, Tel Aviv University researchers have discovered a better model – mice with type 1 diabetes that actually develop MS and can thus be used to test the mechanisms and potential treatments. The researchers hope this breakthrough could lead eventually to the development of better treatments and maybe one day a cure. The research was recently published in Experimental Neurology.
In people, the “shorting” of electrical signals inhibits their transfer between neurons, often leading to devastating disabilities such as blindness and paralysis. Active periods of MS last for anywhere between a few minutes to weeks. These attacks are caused by lesions in the brain that develop, partly recover and then recur. The more attacks there are, the greater the risk of permanent disability.
Israeli scientists are among the prime developers of medications such as Rebif and Copaxone that shorten attacks and reduce their intensity. But research into a potential cure has often been stymied by the lack of a genuine animal model for the human disease. MS does not present in this model as it does in human sufferers – most mouse models experience a single inflammatory peak that leaves them with permanent symptoms such muscle paralysis. But the damage can be detected in the spinal cord, not in the brain.
Dr. Dan Frenkel of TAU’s neurobiology department, working with Prof. Yaniv Assaf and doctoral student Hilit Levy, is likely to boost research by producing a better model. The team discovered that when mice with type 1 diabetes are injected with myelin protein, they suffer periods of relapsing and remitting disability associated with brain lesions in man. And for the first time, they’ve been able to monitor this brain lesion process using magnetic resonance imaging.
“We discovered that when we gave them the same myelin protein injection, a mouse model that develops type 1 diabetes will instead show peaks of inflammatory responses similar to those of chronic progressive MS, which relapses and remits,” Frenkel says. The mice also suffer from brain lesions in addition to spinal cord damage, making them a more viable model for studying and developing treatment for MS in humans.
Using a special MRI machine for imaging small animals, the researchers followed each mouse model over the course of several months, noting the activity of the brain and the development of lesions corresponding to peaks of inflammation. The lesions and the inflammation in the brain can be followed in the same way within these animals as in a human with MS, says Frenkel. “Now, we can follow the different stages that occur after the autoimmune response is already triggered and look for different targets that will not only help to enhance recovery, but prevent further damage as well.”
All MS drugs approved by the US Food and and Drug Administration, including Copaxone, were developed using the EAE model. Their focus has been to delay the clinical signs of the disease caused by autoimmunity, lengthening the time between attacks. But there is no cure.
With his alternative mouse model, Frenkel says, researchers can gather more information on how the brain heals after an attack and start to develop treatment options that mimic this natural recovery process, turning temporary recovery into permanent repair.
“With the use of magnetic resonance imaging, we can follow the brain lesions within the mouse model, and characterize the process of relapsing,” Frenkel concludes. They have already begun to develop treatments with initial success. “We are looking at ways to encourage the glia cells in the brain that support the neurons to promote brain repair.”