Another preclinical study has generated a promising new Alzheimer's treatment--a synthetic compound developed at the University of Minnesota.

The drug, dubbed psi-GSH, helped prevent Alzheimer's-related neurodegeneration in mice. Researchers with the university's Center for Drug Design gave it over 11 weeks to mice predisposed to develop Alzheimer's, and they documented measurable improvements in memory and cognition. What's more, the treated mice lacked any significant brain plaque, and the drug appeared to reduce the buildup of excessive amounts of amyloid beta protein considered a hallmark of the disease.

By contrast, untreated mice experienced significant cognitive declines, and they faced significant plaque buildup in their brains. How did the drug work? According to the researchers, it appeared to help boost the brain's glyoxalase system so it could halt a process that turns normal brain amyloid protein into the distorted variety that leads to Alzheimer's. Previous research determined that Alzheimer's impairs the brain's ability to wield the glyoxalase system, the scientists explain.

The hope here, is that the results give drug developers a new target for which to develop new anti-Alzheimer's drugs. And while other Alzheimer's drugs have failed as they advanced to human trials, the University of Minnesota team said their drug has merit because it hits a root cause of the disease at a very early stage, enabling the brain itself to fight back.

Lead researcher Robert Vince is careful to note that the finding is far from certain in presenting a definite course of action against Alzheimer's. He notes in a statement that the finding is encouraging, but that the results must be repeated in human studies before any final conclusions can be made. Human trials are a long way off, but the research is likely to continue. Details of the findings, meanwhile, are published in the American Chemical Society journal ACS Chemical Neuroscience.

- here's the release
- read the journal abstract

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Massachusetts General Hospital/Harvard scientists have developed a new drug candidate that appears to successfully reduce and protect against Huntington's disease damage in two mouse studies. Its target: blocking the activity of SIRT2, an enzyme that regulates a number of cellular functions.

Both mouse studies involved twice-daily injections of AK-7, a SIRT2 inhibitor that is brain-permeable. The mouse groups had two different variations of Huntington's disease, one with rapid progression and really bad neurological symptoms, and the other, a genetically similar version to human Huntington's disease that was also fairly aggressive.

Both studies involved injections of AK-7 twice daily at three different dose levels beginning at four weeks and culminating at 14 weeks. Both studies improved motor function in the mice, lessened neurological damage and lengthened life spans. But the mouse study with the genetic variation closer to human Huntington's disease--the 140 CAG Htt knock-in model--helped maintain normal motor activity compared with untreated mice with the condition, all of which faced a rapid decline. These mice also had major improvements in brain function, according to the study.

This is obviously early work here, but the results help narrow the focus for subsequent drug development work and show the potential of SIRT2 inhibitors to treat Huntington's. Existing drugs don't slow Huntington's progression, but the researchers argue that their work shows that stronger SIRT2 inhibitors could lead to drugs that hold back rapid progression of the neurodegenerative disease. They plan on testing stronger SIRT2 inhibitors in future Huntington's mouse trials to further test their theory. The treatment may be a long way from human trials, but the preclinical testing goes forward.

For details, read the journal Cell Reports.

- read the release
- here's the journal summary

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Amgen ($AMGN) has an interesting new weapon in the battle against obesity. The company's scientists successfully used an antibody they discovered to make obese monkeys thinner, and also lower their levels of insulin, glucose and triglycerides.

Bloomberg offers a great summary of the study, which is detailed in the journal Science Translational Medicine. In short, the overweight monkeys lost 10% of their body weight. But according to the story, plans aren't set yet when, or whether, Amgen will start testing the antibody, mimAb1, in humans. As the article notes, however, the results point a possibly new way to treat humans with diabetes and obesity.

More animal studies are needed before they reach that point, however, and there are no guarantees that the results can be repeated in human trials. That said, the Amgen researchers have a new drug with promise if subsequent testing can repeat the initial results, and ultimately prove the compound is safe to use. Their antibody is meant to mimic FGF21, a metabolic hormone in humans that regulates both glucose and lipid metabolism. Previous studies have shown that mice bread to produce FGF21 in abundance remained thinner and lived longer (though their bone density declined), the article explains.

But researchers haven't succeeded in making a drug out of FGF21, because its effects only last an hour or so, according to the story. But mimAb1 could be a much more viable drug because it lasted over a period of weeks after just two injections during the 11-week trial.

Obesity drugs don't get approved very often. According to the Bloomberg story, Vivus' ($VVUS) Qsymia and Arena Pharmaceuticals' ($ARNA) Belviq, both approved this year, were the first to gain the FDA's nod to treat obesity since 1999.

- read the Bloomberg story
- here's the journal abstract

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German and French researchers are collaborating across the border to develop an approach that uses the body's own painkillers to cut inflammatory pain, a form of pain that rarely responds to conventional therapies.

Pain is a big deal for patients, especially inflammatory pain. It's hard to treat and the most effective drugs have some real downsides. The side effects of opioids include nausea, drowsiness and constipation, and the drugs can be addictive, and nonsteroidal anti-inflammatory drugs (NSAIDs) can lead to stomach ulcers and bleeding, and may increase cardiovascular risk. What better way then to treat pain by using the body's own painkillers? Especially as blocking pain right where it starts might prevent the development of chronic pain.

The body tries to handle pain itself, by releasing endogenous opioid peptides including enkephalins and endorphins. However, these effects are curtailed by two naturally occurring enzymes, aminopeptidase N (APN) and neutral endopeptidase (NEP).

The aim of researchers at the Charité-Universitätsmedizin Berlin and the Université Paris Descartes is to stop this breakdown in the inflamed tissue. They found that blocking one, the other, or both of the enzymes in animals using inhibitors reduced or stopped the pain.

"Targeting of endogenous opioid peptides directly in injured tissues might be a promising strategy to treat inflammatory pain without serious side effects," states professor Halina Machelska-Stein of Charité-Universitätsmedizin Berlin.

To find out more, look at the study in The FASEB Journal.

- read the press release
- see the abstract in The FASEB Journal

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U.K. researchers have found a way to make stem cells from blood.--Courtesy of University of Cambridge

U.K. researchers found a less painful way to source samples to make stem cells, using blood rather than biopsies, and their findings could pave the way to treat cardiovascular disease and rebuild patients' hearts and other organs.

The research, led by scientists from the University of Cambridge, used blood cells called late-outgrowth endothelial progenitor cells (L-EPCs) from healthy people and patients with pulmonary arterial hypertension (high blood pressure in the blood vessels in the lungs) to create patient-specific induced pluripotent stem cells (iPSCs). L-EPCs normally repair damaged blood vessel walls, but once they become stem cells, they can be triggered to transform into any other type of cell in the body. The study was published in Stem Cells: Translational Medicine.

Pluripotent stem cell therapies are a buzz topic in biotech research, with their amazing potential to rebuild, repair and replace any type of tissue, from new muscle through new hearing cells to new bone, and could create a range of therapies for disorders such as diabetes, infertility and Alzheimer's disease. Scientists have previously created patient-specific pluripotent cells from patients' own skin cells. While these avoid the controversy linked with embryonic stem cells, and aren't at risk of rejection like donor cells, they still need to be grown from biopsies of skin and other tissues, which are painful and invasive. Using blood is simpler, because it is easy to sample, and blood draws are already taken routinely from patients undergoing treatment. Other advantages of using blood cells is that they can be frozen and turned into iPSCs at a later date, unlike other cells that have to be transformed as soon as they are sourced.

"It's a hell of a lot easier to get a blood sample than a high quality skin sample so that's a big benefit," says Chris Mason of University College London, U.K.

Researchers have raised concerns about iPSCs increasing cancer risk. However, these blood-based cells could be safer than those derived from skin cells, as Amer Ahmed Rana of the University of Cambridge told BBC News. "The fact that these appeared to be fairly stable is very promising," he said.

This is early research, and so it's not yet clear whether treatment with these stem cells would be safe or effective. The next step will be to carry out clinical trials, though there are likely to be a lot of challenges to overcome first. As Mason explained to BBC News, the iPSC concept is still very new, and "we need far more experience to totally reprogram a cell in a way we know to be safe."

- read the piece in BBC News
- see the paper (pdf)
- check out the article

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