Wednesday, July 25, 2012

FOXNews.com: New 'one-size-fits-all' drug could treat Alzheimer's, MS and brain injury

FOXNews.com
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New 'one-size-fits-all' drug could treat Alzheimer's, MS and brain injury
Jul 25th 2012, 14:44

Alzheimer's, Parkinson's disease, multiple sclerosis and traumatic brain injury are four neurodegenerative disorders with very different – and very devastating – effects on the brain and daily life. 

While there are multiple treatments and therapies aimed at fighting each of these conditions separately, a team of researchers from Northwestern University Feinberg School of Medicine have developed a new "one-size-fits-all" therapy drug that could potentially treat all of them.

The drug's trick lies in reducing a particular type of inflammation in the brain known as neuroinflammation.  This brain response has become increasingly considered a common denominator for many neurological disorders, as well as playing a major role in brain injuries.  To decrease inflammation, the drug developed at Northwestern binds to and decreases a molecule known as cytokine, which is released in large quantities during the neuroinflammatory response.

"We faced two main challenges," Dr. Martin Watterson, a professor of molecular pharmacology and biological chemistry at the Feinberg School, as well as the lead developer of the drug, told FoxNews.com.  "Come up with something to tone down the inflammatory response and do it with some selectivity [so that the immune response would not be toned down as well].  "We wanted to have a small molecule taken by mouth once or twice a day that would be relatively safe and get into the brain."

Published in the Journal of Neuroscience, the study showed the success of the drug in preventing progression of Alzheimer's in mice that were genetically engineered to develop the disease.  When the mice were evaluated 11 months after being administered the drug, their inflammation had decreased, and their brain synapses were functioning normally.  

While the results are encouraging, Watterson said there's still some ways to go.

"The design, the synthesis and testing [of the drug] took less than a year," Watterson added.  "In drug development, that's called a hit.  It's like a bite when you're fishing, it's significant, but you still have to reel in the fish… You have to take the hit and improve on it to get a lead compound which has better activity in vivo and does not have bad activity."

Stopping brain diseases in their early stages

Unlike the majority of existing treatments for neurological disorders, this class of drugs – labeled MW151 and MW189 – takes a new approach by targeting the disorders during the early to middle phases of the inflammatory response.  Current treatments for these conditions target the development of beta amyloid plaques in the brain, a common indicator of the diseases' progression; however, the new drug developed by Watterson and his team targets the increase of the cell-signaling molecule cytokine, a precursor to the development of neurodegenerative disorders.

"In the nervous system, the neurons and glia work together, and when they neurons get stressed, they send signals out and tell the glia, 'I'm being stressed, I'm being attacked,'" Watterson said. "The glia then releases cytokine and other molecules [to attack the stressors].  What happens with disease progression is this cycle gets out of control and you get innocent bystander effect, which cause the synapses in the brain to become attacked as well."

The longer cytokine production increases and becomes uncontrollable, the more damage is done to the neurons; and if they are stressed for too long, they wither and essentially die.  That's why, Watterson said, this period of time is the target window for taking the drug – to save the neurons.

"That's one of the problems with Alzheimer's, people have been targeting therapies to go after late stage, and people think those are failing because it's too late," Watterson said, noting the most recent failure of Pfizer's experimental Alzheimer's drug in one of its four major trial.  "This is something that the Alzheimer's community has been talking about now for two to three years, is that you need to treat early."

Given this prerequisite for timing, the drug must be taken before the disease progresses, rendering it ineffective on people whose conditions have progressed into the later phases.  But according to Watterson, if administered during this target window, this drug could potentially combat any disease in which there is excessive cytokine production – including anything from progressive disorders such as Alzheimer's and MS to the devastating effects of acute brain injury.

"It's already been shown that with acute injury, you have this acute window when the cytokines get out of control," Watterson said. "…We're making the point that about the point in the animal model where you see the cytokines going up, that's about the time you see mild cognitive impairment in patients, a precursor to Alzheimer's."

Now that the drug has been shown to be safe to use in humans, Watterson and his team are waiting for funding from a biotech company to start clinical trials.  Watterson hopes that this drug would not serve as a replacement for current therapies targeting neurodegenerative disorders, but could be used in combination with other drugs to stop these conditions in their tracks.

"Maybe neurologists would get the test [for cytokine production], send the results to radiology to get an MRI scan, and maybe they'd take a blood sample or spinal sample," Watterson said of future testing. "Then they could start them on the drug to see if it improves the outcome.  The body has tremendous repair mechanisms.  It could be you just have to give them enough to slow down the process so the body can repair itself."

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