(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.
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.
Israel acts to plug brain-drain
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.
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
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.
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
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.”