MEDICAL BREAKTHROUGHS

[AAP, August 4, 2005]

A drug that slows the progression of Alzheimer's disease could be available in less than five years after a world-first discovery by Australian researchers. The research team, led by neuroimmunologist Dr Gilles Guillemin of the University of NSW, has discovered a toxin that plays a key role in the development of Alzheimer's, the most common cause of dementia. The toxin, called quinolinic acid, kills nerve cells in the brain, leading to dysfunction and ultimately death.

More than 200,000 people have Alzheimer's disease in Australia and the figure is expected to rise to 730,000 by 2050.

Professor Bruce Brew, director of neurology at Sydney's St Vincent's Hospital, said if the production or effect of quinolinic acid could be blocked then it could slow the disease's progression. "We're not saying that quinolinic acid is the cause of Alzheimer's disease ... we're saying it's a player in the causation," Professor Brew told reporters. “It could trigger the disease or amplify the damage.”

Quinolinic acid is part of a biochemical pathway called the kynurenine pathway, which is also found in other major brain disorders including Huntington's disease and schizophrenia.

Professor Brew said there were several drugs in the advanced stage of development for other conditions which targeted this pathway. These drugs, which would need to be tested, could be used to complement other treatments for Alzheimer's.

“I can only speculate on the effect of the drugs, but expected it to be positive,” he said. "These drugs have been designed to fight some aspects of the pathway, the biochemical pathway which produces the acid, and also designed to fight a mechanism of how this toxin causes cell death.

"Building on what we've found and others have found, it's likely that they would have significant effect. It is likely to be some years before the drug would be available, but it's not the scenario where you have to develop a drug from scratch and you look at five or 10 years."

At present, there are only minimally effective treatments for the disease, which is increasing with the ageing population.

The study is a result of a collaboration between researchers from St Vincent's Hospital, the University of NSW, the University of Sydney and Hokkaido University, Japan.

[World Science, Nov. 25, 2006]

For researchers, as for society at large, marijuana has been among the most bedeviling of drugs. Some studies have found that the illicit substance damages the memory. Others suggest that it doesn’t, or even that it may be beneficial for some conditions including Alzheimer’s disease. Through it all, the public clamors for answers—desperately needed to help resolve a decades-long, raucous debate over whether pot is safe enough to be legalized.

A group of scientists now proposes that the answer may be more complex than either side in that debate would have us believe. Marijuana may have played a trick on us all, they suggest, playing the roles of both health villain and hero. In hefty doses, they argue, its active ingredient may help protect the brain against various types of damage. But in tiny doses, harmful effects come through, they add.

Those damaging doses would be much lower than those normally taken in from smoking in a marijuana cigarette, argues Yosef Sarne of Tel Aviv University in Israel, a member of the research team. On the other hand, he adds, a large dose inevitably becomes a small one as the body clears it out—so perhaps a user can never sidestep the dangers completely.

The team presented its findings in the Nov. 6 issue of the research journal Neuroscience Letters. The active compound that produces the “high” in marijuana is called delta nine tetrahydrocannibanol, or THC for short. This and related compounds, in high doses, tend to restrict the release of a chemical called glutamate from brain cells, Sarne and colleagues argued. This can be helpful because excess release of glutamate—otherwise a normal and essential chemical messenger in the brain—is implicated in various disorders, including Alzheimer’s.

This may explain why compounds in the THC family, called cannabinoids, help protect brain cells in cases such as ischemia, or blocked blood vessels; excitotoxicity, or overstimulation of nerve cells; or blows to the head. Studies suggest that cannabinoids seem to suppress glutamate release by partially blocking molecular gateways in nerve cells, known as voltage-dependent calcium channels, Sarne and colleagues wrote. But ultra-low doses appear to have the opposite effect, they added.

Thus the researchers hypothesized that “an acute treatment results in a high concentration of the drug close to the time of trauma and therefore protects the brain from the acute insult, while chronic treatment exposes the organism to low concentrations of cannabinoids for long periods of time.” During that time, “minor” nerve cell damage accumulates. In the Neuroscience Letters study, Sarne and colleagues injected mice with THC doses that they said were some 1,000 times lower, taking into account body weight, than what humans would get from smoking a joint. The treatment significantly worsened the rodents’ performance on maze tests three weeks later, compared to untreated mice, they wrote.

Exactly how the chemical damages the brain remains unclear, Sarne’s team wrote, as are the implications for humans. “Human subjects may overcome such minor deficits,” they wrote. Some brain imaging studies have found that frequent smokers “can compensate for subtle cognitive deficits by enlisting larger brain regions or by recruiting additional brain areas.... Yet, such subtle deficits might emerge under certain behavioral or physiological conditions.” The importance of this research goes “beyond its scientific significance,” the team wrote in a previous paper, published in the journal Medical Hypotheses in 2004.

“Cannabinoids are the most widely used drugs of abuse. In spite of the many reports on their long-term neurotoxic effects, cannabinoids are still considered by many as ‘safe soft drugs,’” and their beneficial effects are often cited to back up claims for their long-term safety. “The clear dissociation between these two modes of action, and the demonstration that cannabinoids induce long-term cognitive deficits, may help to draw the public awareness to the deleterious consequences” of chronic pot use, as well as clarifying the drug’s clinical benefits. Cannabinoids are used or under consideration for use, they noted, to fight pain and inflammation, prevent vomiting and nausea from chemotherapy, stimulate appetite in AIDS and anorexia patients, and to treat muscle spasms associated with multiple sclerosis.

WORLD SCIENCE WEBSITE

[World Science, July 27, 2005]

A commonly used class of drugs could extinguish the trauma associated with horrific memories, according to a news article in this week’s edition of the research journal Nature. The findings could help people with post-traumatic stress disorder—a psychological condition that results from traumas like war or terrorist attacks, researchers said in the journal.

But some mental health experts also worry treatment could be abused, the article noted, perhaps by military commanders who want soldiers to become desensitized to terrible acts.

The drugs are known as beta-blockers, and they are already widely used as treatments for high blood pressure and heart problems. According to the journal, U.S. psychiatrists claim beta-blockers can also interfere with the way the brain stores memories. Administer these drugs at the right time, suggest the psychiatrists, and sufferers of post-traumatic stress disorder could snuff out the periods of panic that blight their lives.

The idea is timely, yet controversial. Data on previous terrorist attacks suggest that the recent bombings in London and Egypt will cause a spike in post-traumatic stress disorder rates. Current treatments, such as counselling, have limited success, so alternatives are welcome, the journal noted.

According to Nature, research in rats has shown that beta-blockers disrupt the process by which the brain puts a memory back into storage after it’s recalled. In so doing, they don’t erase the memory completely, but they can extinguish the fear and panic associated with it. The drugs act by blocking neurotransmitters, chemicals that transmit messages among brain cells. To work, they would have to be administered at the time patients are feeling symptoms of the stress disorder, such as rapid heart rate or troubled breathing.

A group of New York-based psychiatrists including Margaret Altemus of Cornell University has reproduced some of the rat results in humans, and plans to submit their findings for publication in a research journal, Nature reported. In the meantime, they are starting work on a clinical trial of one beta blocker, propanolol.

But other researchers told the journal that they have concerns about the research. Paul McHugh, a psychiatrist at Johns Hopkins University in Baltimore, Maryland, and a member of the U.S. President’s Council on Bioethics, was quoted as saying: “If soldiers did something that ended up with children getting killed, do you want to give them beta-blockers so that they can do it again?”