November 17, 2003
New Orleans, LA
Understanding the signals to turn on specific genes in the brain with proteins might enable the modulation of an immune attack to the brain like that of Multiple Sclerosis (MS), according to a study presented here November 8th at the Society for Neuroscience 33rd Annual Meeting.
Stephen J Crocker, PhD, Department of Neuropharmacology, Scripps Research Institute, La Jolla, California, presented the study.
Dr. Crocker's lab is funded by the National Multiple Sclerosis Society, and focuses on the study of a family of enzymes called metalloproteinases. These enzymes are important because they are released by human immune cells, and allow attacks on the brain, leading to diseases such as MS, Alzheimer's and Parkinson's.
What the researchers found in this study was that the brain responded to an immune attack by producing an expression of other proteins, called Tissue Inhibitors of Metalloproteinase (TIMPs), or endogenous tissue inhibitors.
"The brain responds by trying to prevent these genes," Dr. Crocker explained.
The purpose of this study was to discover and try to work out what specific signals the brain was using to turn on the protective response.
"What we found was that the non-neuronal cells in the brain -- microglia and astrocytes -- only respond to very specific chemical messengers related to inflammation," said Dr. Crocker. "By understanding which signals are required to turn on these specific genes, we might therein be able to modulate the degree and severity of an immune attack to the brain like MS."
This finding could apply to all similar attacks on the brain, including Alzheimer's and Parkinson's.
"It is quite clear that these may be important regulators of [brain] injury related to the immune system," he said.
Future therapy might include blocking these enzymes, reducing the injury to the brain, or enhancing the brain's ability to produce these proteins.
"[One] might be able to provide a superior therapeutic strategy," Dr. Crocker noted.
Beta-interferon is now provided to MS patients for treatment, but some research shows it has no direct on expression, Dr. Crocker indicated. It may be regulating the enzymes on the other side of the equation.
"While we are in our infancy in understanding these proteins in the brain, it's clear from our work, and [from that of] others looking at neurodegenerative conditions, that these proteins clearly have a great deal of potential."
The brain was once viewed as an "immune privileged area," protected by the "blood brain barrier," said Dr. Crocker. "That's clearly no longer the case. Inflammation is the ubiquitous feature of neurodegenerative conditions. From Parkinson's to MS, these proteins may play a role in all of them."
Dr. Crocker indicated that the idea of tweaking the immune system is getting a lot of attention in the drug industry. "It's on the horizon," he said. "How we might be able to train [these proteins] to work for us, instead of against [us], is what's going to come next."
[Study Title: Cell-and Agonist-Specific Regulation of MMP and TIMP Gene
Expression in Cultured Glial Cells. Abstract 105.5]
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