Drug For Alzheimer’s, Parkinson’s And MS Shows Promise

A “one-size-fits-all” new class of drugs that targets a particular type of brain inflammation is showing early promise for the treatment of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and traumatic brain injury.

A pre-clinical study due to be published this week in the Journal of Neuroscience shows one of the drugs stopped mice bred to have Alzheimer’s from developing the full-blown disease.

The new class of drugs, developed at Northwestern University Feinberg School of Medicine in the US, approaches the treatment of Alzheimer’s differently to the ones currently being tested to prevent beta amyloid plaques in the brain. While the plaques are known to indicate Alzheimer’s, nobody has yet proved that they cause the disease.

A press statement released on Tuesday reveals Northwestern has already been issued with patents to cover the drugs and has licensed commercial development to a biotech company that has just completed the first phase 1 clinical trial which tests safety in humans.

The new class of drugs, currently known as MW151 and MW189, target a particular type of brain inflammation that is a common denominator in MS, Alzheimer’s and Parkinsons, and also in traumatic brain injury and stroke.

More and more scientists are coming round to the idea that inflammation plays a major role in the progressive damage that characterizes these chronic neurological diseases and brain injuries.
Pre-Clinical Study in Alzheimer’s Mouse Model
In the pre-clinical study that is to be published this week, researchers from Northwestern’s Feinberg School and the University of Kentucky, report that when one of the drugs, MW-151, is given to a mouse genetically engineered to develop Alzheimer’s, it stops progression to the full-blown disease.

The results suggest giving the drug before Alzheimer’s symptoms are readily apparent may be a promising therapeutic strategy.

The drug is a selective suppressor of brain inflammation and overproduction of proinflammatory cytokine molecules from glial cells, the cells that surround, nourish, protect and support neurons.

The study identified the optimal time window for giving the drug, which is taken orally and crosses the blood-brain barrier.

It tested the idea that drugs like MW-151 could be preventive, when given at an early stage before Alzheimer’s pathology appears, as well as after disease symptoms have begun to appear.

The results showed that the drug was effective when given either before or after Alzheimer’s was apparent, but was most effective when given before symptoms were too advanced.

Co-lead author Linda J Van Eldik, director of the University of Kentucky Sanders-Brown Center on Aging, told the press:

“Early intervention with MW-151 in an Alzheimer’s mouse model reduced the glial activation and proinflammatory cytokine overproduction, which resulted in improvement in neurologic outcomes.”

“The neurological outcomes included protection against the loss of critical nerve cell proteins and functional damage associated with learning and memory impairments,” she added.
Targeting Glia Cells
Even though it is not clear what role inflammation plays in the brain, the main target of the drug is the overproduction of cytokines that promote the inflammation.

Glia cells produce proinflammatory cytokines and other immune responses to injury or disease progression. They normally cooperate with neurons or nerve cells to keep the brain running smoothly.

When an injury or change occurs, the glia cells cause beneficial inflammation, an immune response that brings in chemicals to deal with the damage and help restore the brain to normal functioning.

But sometimes, this beneficial response gets out of hand: the inflammation is too strong or does not shut off when the job is finished.

This results in too many cytokines, which causes the synapses of the brain to misfire, and eventually the whole organization of the brain falls into disarray, like a computer malfunction. Neurons can’t pass signals to each other, and can eventually die.

The resulting damage in the cortex and hippocampus can compromise memory and decision-making.

In Alzheimer’s Disease, the glia cells are over-activated and produce too many cytokines.

Drugs that selectively target levels of cytokine production in glia cells are logical first attempts at developing treatments that follow this approach.

“In Alzheimer’s disease, many people now view the progression from mild cognitive impairment to full-blown Alzheimer’s as an indication of malfunctioning synapses, the pathways that allow neurons to talk to each other,” said study co-author D. Martin Watterson, a professor of molecular pharmacology and biological chemistry at the Feinberg School, whose lab developed the drug.
Drug Kept Cytokine Levels Normal
In the pre-clinical Alzheimer’s study, the researchers gave the mice MW151 three times a week starting at six months of age, right at the time the proinflammatory cytokines began to rise. This is roughly when a human patient would begin to experience mild cognitive impairment.

When they examined the mice brains at 11 months (the age when signs of the disease can be detected), cytokine levels in the mice that received the drug were normal and synapses were functioning normally.

The inflammatory cytokine levels of the mice that did not have drug, however, were still abnormally high, and their synapses were misfiring.

“The drug protected against the damage associated with learning and memory impairment,” said Van Eldik, “Giving this drug before Alzheimer’s memory changes are at a late stage may be a promising future approach to therapy.”
Other Neurological Diseases and Brain Injuries
In previous animal studies, the same drug tested in the mouse model reduced the neurological damage caused by closed-head traumatic brain injury and inhibited the development of a multiple sclerosis-like disease.

For instance, in a study where mice bred to develop multiple sclerosis (MS) were given MW151 orally, they did not develop the disease as severely.

Currently, the only oral drug treatment for MS acts on the lymph nodes, and not on the brain, where the inflammation and damage occurs.

In another study with mice, researchers showed that giving MW151 during an early therapeutic window three to six hours after traumatic brain injury, blocks glial activation and stems the ensuing flood of proinflammatory cytokines.

The researchers in those studies said therapies based on this class of drug could be a way to prevent or reduce the long-term complications of brain injury or even stroke, such as seizures, cognitive impairment and, perhaps, mental health issues.

These studies show that for these conditions, including Alzheimer’s, the therapy time window was critical.

Watterson said:

“We need more studies of therapeutic time windows in models of these other diseases so we can better plan future clinical trials.”

Grants, awards and gifts from various bodies, including the American Health Assistance Foundation, Alzheimer’s Association, Kleberg Foundation, and various organizations within the National Institutes of Health (NIH), helped pay for the study.

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