Medivation Alzheimer's drug helps -- if used early

A drug for Alzheimer's disease made by Medivation Inc kept symptoms at bay for 18 months, U.S. researchers said on Wednesday, but people who got the drug after first taking a placebo fared less well, suggesting early treatment is best.The latest results, being presented at the Alzheimer's Association's international meeting in Chicago, found Dimebon was safe and continued to benefit people who took it for a year and a half.

"The most important thing from my point of view is there were no new safety issues that emerged with longer exposure of the patients," said Dr. Jeffrey Cummings of UCLA, who helped with the study.

The results from the 183-patient study conducted in Russia found people continued to improve, with benefits seen in cognition, memory, activities of daily living and behavior.

The study also found that people who were treated with a placebo for a year and then took Dimebon stabilized across five measures of thinking ability, but were unable to catch up to the group who had taken it for the full 18 months.

"People initially treated with the placebo and then crossed over to Dimebon did not show the same level of benefit as those people who took Dimebon for the full 18 months," Cummings said in a statement.

"This emphasizes the benefit of earlier treatment and suggests the possibility that Dimebon may slow the progress of Alzheimer's," he said.

Medivation has provided frequent updates of patients in the study in Russia, where patients in the study took few if any drugs other than Dimebon.

Such a study would not be possible in Western countries, where most Alzheimer's patients take a variety of other drugs.

Some doctors think the true test of whether Dimebon represents an advance over current therapies will come from studies done in the West, where patients have ready access to other drugs that can slow progression of the disease.

These include Eisai Co Ltd's and Pfizer Inc's Aricept, Forest Laboratories Inc's Namenda, Novartis AG's Exelon and Johnson & Johnson's Razadyne.

All affect message-carrying chemicals in the brain called neurotransmitters, but lose their effect over time.

"The one issue with this trial is that no other treatments were allowed," Dr. Scott Turner, incoming director of the Memory Disorders Program at Georgetown University Medical Center in Washington, said in a telephone interview.

"Here it will be tested as an add-on, and the question is will it have any other benefit (when taken) with the current therapies," he said. "I think that is a big if."

Cummings thinks the drug has a shot.

"I think we will continue to see an effect because the signal was strong; but under the circumstances of a global trial, it will likely be not as clearly seen as it was in the Russian trial," he said in a telephone interview.

In late afternoon Nasdaq trading, Medivation shares were down 84 cents or 4.3 percent to $18.93.

Lilly says Alzheimer's antibody drug safe

Eli Lilly and Co's antibody drug for Alzheimer's disease was safe and appeared to be dissolving sticky brain plaques, but a three-month study was too short to show any improvement in memory, company researchers said on Wednesday.The infused therapy, known by the experimental name LY2062430, attempts to remove a brain-damaging protein called beta amyloid via antibodies that attach to individual, free-floating molecules of the protein before they can form clumps known as plaques.

"The safety profile for our antibody seems to be very, very good. We were not able to identify any side effects we could relate to the antibody," Dr. Eric Siemers, medical director of Lilly's Alzheimer's disease research, said in an interview.

That may be significant.

People with Alzheimer's disease have too much beta amyloid plaque in the brain, and the prevailing theory is that removing the plaque may slow disease progression.

Rivals Elan Corp Plc and Wyeth, which are developing a drug with a similar approach, said on Tuesday that 12 people in a larger, longer study treated with their antibody developed vasogenic edema, a condition marked by a build-up of fluid in the brain, although the side effect appeared to be manageable.

Siemers said the Lilly drug may avoid damaging the brain because it does not attack plaque. "It binds to individual amyloid beta molecules," he said.

FINDING THE TOXIN

"One of the big questions is what is really the toxic part of beta amyloid. There is good evidence that it is not the plaque itself," said Siemers, who presented the findings at an Alzheimer's Association conference in Chicago.

Lilly's study involved 52 people with mild-to-moderate Alzheimer's disease and 16 healthy people who received 30-minute infusions of the drug or a placebo for 12 weeks.

The goal was to test for safety and to see if tests of blood and spinal fluid could detect changes in protein levels that would suggest it was working.

They found that after giving the antibody, more beta amyloid appeared in patients' blood and spinal fluid. The company sees this as a sign the antibody is clearing out the beta amyloid.

They used a type of brain imaging known as SPECT to measure plaque in the brains of 24 Alzheimer's patients and 13 healthy people.

In people who got the highest dose of the antibody, a type of beta amyloid typically found only in plaque appeared in their blood. "It appears the plaque started to dissolve around the edges," Siemers said.

The study found no evidence that this made any difference at improving memory, but Siemers said researchers did not expect it would in such a short time.

Lilly will move to longer, larger studies next year to see if the treatment can alter mental decline. Siemers acknowledged that the larger studies may turn up side effects not seen in the smaller study.

Meanwhile, he said the company is pressing ahead with a drug using a completely different approach. It targets an enzyme called gamma secretase that is thought to be involved in making beta amyloid.

The aim of that drug is to interfere with the production of beta amyloid before it can build up in the brain.

Myriad Genetics Inc's Flurizan, also called tarenflurbil, targeted gamma secretase and showed promise in mid-stage trials but failed to show any benefit in a large study released last month.

Moms With Alzheimer's May Pass on Risk to Kids

People whose mothers have had Alzheimer's disease may be predisposed to the mind-robbing condition, a new study finds.The link may be a dysfunction in how the brain handles sugar -- something that's probably genetic and starts years before symptoms of Alzheimer's appear, researchers say.

"Overall, these findings show that their brains are not working properly to start with, and the metabolic impairment gets worse over time," explained lead researcher Lisa Mosconi, a research assistant professor of psychiatry at the Center for Brain Health at NYU Langone Medical Center in New York City.

There is evidence that having a parent affected with Alzheimer's disease increases the risk of developing Alzheimer's disease four- to tenfold, Mosconi said. "However, we don't know why or how this happens. Our study shows for the first time that individuals with an Alzheimer's disease [-affected] mother may be at increased risk for developing Alzheimer's disease themselves because their brains are not utilizing glucose in an effective way," she said.

The findings were to be presented Wednesday at the Alzheimer's Association's International Conference on Alzheimer's Disease in Chicago.

For the study, Mosconi's team used PET scans to look at glucose metabolism in the brains of 66 healthy individuals. Some of the participants had a family history of Alzheimer's disease, and some did not.

The researchers found that people with a mother with Alzheimer's had a much faster progressive reduction in the use of glucose in areas of the brain affected by the disease, compared with people who had a father with Alzheimer's or parents without the disease.

"At this point, we can only speculate that genes that are maternally inherited may alter brain metabolism," Mosconi said. "We need to follow subjects for longer time periods to ascertain whether the metabolic reductions are in fact forerunning cognitive deterioration."

Early diagnosis is extremely important, particularly while people are still symptom-free and treatments are most effective, Mosconi said. In addition, maintaining overall good health will help protect brain health, she said.

"This includes checking for blood pressure, cholesterol levels, glucose levels, arteriosclerosis and vascular damage in general, because improving cardiovascular health is particularly important to also promote brain health," Mosconi said. "If an individual finds out that they are at risk for developing Alzheimer's disease and are not taking much care of their health, that's already a good reason to start immediately."

Dr. Sam Gandy, chairman of the Alzheimer's Association's National Medical and Scientific Advisory Council, believes the findings could prove promising for drug research.

"One could collect the children of mothers with Alzheimer's disease, divide them into a placebo group and a drug-test group, and follow them with neuropsych tests and brain scans to see whether the group receiving the drug had delayed onset or prevention," Gandy said.

Greg M. Cole, associate director of the Alzheimer's Disease Research Center at UCLA David Geffen School of Medicine, Los Angeles, said the findings could help in diagnosis.

"Our best hope is to catch the disease early and treat early," Cole said. "One way of doing this is to identify people with significant genetic risk, but we only know one common risk factor, ApoE4 gene," he said.

Using imaging methods to follow the brain's regional energy use, doctors can detect signs of Alzheimer's in those at risk from ApoE4 many years before developing dementia, Cole said. This study shows similar results in people with a family history who don't have the ApoE4 risk factor, he added.

"This is significant because it broadens the utility of imaging as a tool for detecting the disease early -- not simply in those with a specific form of genetic risk," Cole said. "Now it needs to be paired with clinical trials for new approaches for prevention."

Family History May Add to Alzheimer's Puzzle

The gene most often associated with Alzheimer's disease doesn't provide a complete picture of overall risk, according to researchers who analyzed family histories of the disease.Previous research has shown that people with the E4 variant of the APOE gene have a greater risk of developing Alzheimer's, but this new Duke University Medical Center-led study is one of only a few to examine the role of both APOE and family history together.

"We've learned that APOE genotype does not tell the whole genetic story. Other genes may be acting independently of APOE to influence someone's risk for developing the disease," lead investigator Kathleen A. Welsh-Bohmer, director of Duke's Bryan Alzheimer's Disease Research Center, said in a Duke news release.

The study included more than 5,000 people in Cache County, Utah, who were 65 and older when they were enrolled in the study in 1995. About 3,000 of the participants who provided DNA and details about their family history of Alzheimer's were grouped according to the family history of the disease and whether they had the APOE E4 variant.

"Over an average of seven and a half years of observation, the people who experienced the most significant cognitive decline had a family history of the disease and one or more copies of APOE E4," Kathleen M. Hayden, an assistant professor of geriatric psychiatry, said in the Duke news release.

"For this reason, researchers should focus not only on people at risk because of the APOE gene, but also those who have a family history of Alzheimer's disease. Conversely, studying those who survive to late old age without disease is important to discover genes that may offer protection against the disease."

The study was expected to be presented Tuesday at the Alzheimer's Association's International Conference on Alzheimer's Disease, in Chicago.

"These data provide further evidence that we must explore other genetic avenues to learn more about who is at risk for cognitive decline and dementia," Welsh-Bohmer said.

Advances Made Against Alzheimer's Disease

New reports on very different approaches to treating Alzheimer's disease could one day lead to better therapies for the mind-robbing condition, experts say.A trio of studies that were presented Wednesday at the Alzheimer's Association 2008 International Conference on Alzheimer's Disease in Chicago noted progress made on three different treatment fronts.

The first involves a drug called Dimebon, with positive results being reported from tests in Russia. Dimebon is an antihistamine, and data from the Russian trials indicated that Dimebon might have value in treating Alzheimer's.

This buttressed American research reported earlier this year that showed improvements in Alzheimer's patients given Dimebon in a controlled study. The drug is believed to prevent the death of brain cells.

Researchers at the University of California, Los Angeles, studied 183 people who had mild to moderate Alzheimer's disease. Mental function remained stable in those taking the drug, while it declined in those given a placebo. Mental function also stabilized in people who were first given a placebo after they began taking Dimebon.

Another trial used the body's immune system to prevent the mental deterioration suffered by people with Alzheimer's disease. The immune attack is aimed at the deposits of beta-amyloid protein that accumulate in the brains of patients.

"The idea has been around for almost a decade now," Nixon. "The initial notion was to use the vaccine approach to prevent amyloid deposition, injecting amyloid so the body would attack the deposits. Now we are into phase two, injecting the antibody itself."

Researchers at Eli Lilly & Co. reported on 52 people with mild to moderate Alzheimer's. Some were given weekly injections of a monoclonal antibody that binds to beta amyloid, while others were injected with a placebo.

Detailed measurements showed an increased level of beta amyloid in both blood and cerebrospinal fluid after 12 weeks in those getting the antibody, an indication that the beta amyloid in the brain might be starting to dissolve, the researchers said. New studies of the therapy are planned.

Nixon viewed the results with "tempered optimism." One interesting finding was the response to the therapy was greatest in people who did not have a known genetic marker for Alzheimer's risk, he said. "What is the significance of this? Why do carriers not respond?" Nixon asked. The answer might help explain Alzheimer's disease better, he said.

A third study using a broad spectrum of antibodies was reported by a team at Weill Cornell Medical College in New York City. The treatment, originally developed by Baxter International to treat autoimmune conditions, was given to 24 people with mild to moderate Alzheimer's disease in a set of trials extending as long as 18 months. Statistically significant increases in mental function were seen in those getting the treatment, the researchers said. A large-scale, 18-month follow-up trial will be done.

Flu Vaccine Doesn't Protect Seniors From Pneumonia

Flu vaccine may not protect older people from pneumonia once they get the disease, researchers report.Older, frail adults are more susceptible to getting the flu, even if they have been vaccinated, and once getting the flu, they are more susceptible to such complications as pneumonia. It had been thought that flu vaccine would prevent flu -- and pneumonia -- across all groups of seniors, but this benefit appears to be largely confined to younger, healthier seniors.

"In seniors, flu vaccine was not linked to a reduced risk of pneumonia," said lead researcher Michael L. Jackson, a postdoctoral fellow at the Group Health Center for Health Studies in Seattle.

Jackson still recommends that seniors get flu vaccine, however. "There have been good randomized trials that show, at least in healthy seniors, that the vaccine reduces the risk of influenza," he said. "However, earlier studies have overestimated how well the vaccine works in reducing complications of influenza. So, the vaccine may not reduce the risk of complications as much as previously thought," he said.

Among young healthy seniors, the vaccine reduces the risk of flu, Jackson said. "When you look at the total population of seniors, which includes people over 75 and people that have chronic health diseases -- lung disease, heart disease, diabetes, and things like that -- we don't know if the vaccine is effective in the seniors," he said. "People with these chronic diseases are more susceptible to getting the flu, and they are more likely to develop pneumonia if they do get influenza."

The report is published in the Aug. 2 issue of The Lancet.

For the study, Jackson's team collected data on 1,173 people between the ages of 65 and 94 who developed pneumonia They compared these individuals with 2,346 people who did not get pneumonia. Both groups had similar rates of flu vaccination over the three seasons of studies, the researchers say.

The researchers found that vaccinated seniors who got the flu were as likely to develop pneumonia as unvaccinated seniors who got the flu.

Dr. Pascal James Imperato, dean of the master of public health program at the State University of New York Downstate Medical Center in New York City, was not surprised by these results.

"We know that elderly people do not form sufficient antibodies to certain vaccines, the flu vaccine included," Imperato said. "In addition, people in their 70s and 80s and 90s are more prone to pneumonia with or without influenza. A number of these pneumonias may be secondary to other causes aside from influenza."

Even though many of the elderly will not develop sufficient antibodies to the flu vaccine, getting the shot is still worthwhile, Imperato said. "Having many people vaccinated builds up a herd immunity to disease, and you create barriers to transmission," he added.

Dr. Marc Siegel, a clinical associate professor of medicine at New York University School of Medicine in New York City, said the results of this study fly in the face of prevailing wisdom.

Siegel noted that 36,000 people in the United States die each year from the flu. "Over 90 percent of them are elderly," he said. "We give the flu shot primarily to prevent elderly deaths.

The effectiveness of the flu vaccine varies year to year, however, depending on how good a match it is for the circulating strains of influence. "In the best years, the flu vaccine is really only 40 to 60 percent effective," Siegel added.

In addition, Siegel thinks that the flu vaccine protects against other complication including respiratory diseases, which can also be fatal. "There are plenty of flu-related complications that are life-threatening besides pneumonia," he said.

"This study is a reminder that flu vaccines are not a panacea, but they are valuable, because they cut down on the incidence of influenza," Siegel said. "Flu shots definitely cut down on the number of flu-related deaths."

Alzheimer's Research Holds Promise

When it comes to Alzheimer's disease, there hasn't been much to celebrate in recent years. Efforts to develop a vaccine against the brain disorder have stalled, and no drugs have been able to reverse the slow death of neurons that robs people of their memories and thoughts. For the first time in many years, however, researchers in the field are genuinely excited about the potential for effective drug treatments and helpful new risk factors.Scientists gathered this week at the Alzheimer's Association's International Conference on Alzheimer's Disease in Chicago, presenting a slew of promising results from drug trials, a new understanding of how the neurological disease works and insights into the way social and lifestyle factors may affect its progression. "On the one hand, Alzheimer's disease is a complex pathologic process, and that is daunting," says Dr. Ronald Petersen, chair of the Alzheimer's Association's medical and scientific advisory council and director of the Mayo Clinic Alzheimer's Disease Research Center. "But now we are beginning to segregate out different therapeutic targets and develop drugs that have an impact on each target, so in combination they may handle the disease better than any single approach."

The potential success of the combination strategy was borne out in some of the conference's most exciting papers. Researchers from Mount Sinai School of Medicine reported, for example, that compared with other Alzheimer's patients, those who had diabetes and took insulin plus another anti-diabetes medication to control blood sugar had 80% fewer amyloid plaques - the sticky brain-clogging masses that, together with protein tangles, are the hallmarks of Alzheimer's disease. Although the mechanism wasn't entirely clear, researchers think the drugs may work by normalizing the brain's communication network of insulin receptors, which goes awry in the Alzheimer's brain, while clearing away the damaging plaques.

In a separate trial, an experimental drug called rember, developed by a Singapore-based company, also showed some promise in a safety study. Among 321 patients, rember appeared to stall advancement of the disease, degrading the protein tangles that build up in Alzheimer's brains. Potentially, a combination of drug therapies - designed to prevent both plaques and tangles - may prove effective in slowing the progression of the disease.

But future approaches won't stop with drug treatments. Petersen notes that researchers are also forging ahead with innovative screening tests to identify Alzheimer's patients sooner - before too much deterioration occurs in the brain. Better screens could also potentially identify patients by the specific type of brain buildup - plaques vs. tangles - that is causing them the most severe problems. That kind of triage early on could help doctors target the right patients with the most effective therapies.

Alzheimer's doctors also reported new discoveries about certain lifestyle factors that may accelerate or slow the dementia that often precedes Alzheimer's. Swedish psychologists studied rates of the disease in a sample of 1,449 people over a period of 21 years. They found, as previous research has suggested, that single people have up to twice the risk of developing Alzheimer's as their married counterparts. But what was unexpected was the finding that the reason for a person's singlehood impacts his or her risk. Compared with other singletons, people who were single as a result of divorce or widowing had a three times and six times greater risk, respectively. "This was quite unexpected," says Krister Hakansson, who led the study and is a lecturer in psychology and a Ph.D. candidate at Vaxjo University and the Karolinska Institute. "We established the association, but when it comes to explaining it, we can only speculate at this state."

One reason for the higher risk could be that those who had the cognitive protection and social benefits of a relationship but lost them may be worse off than those who never enjoyed those benefits at all; or perhaps the emotional toll of losing a close partner damages cognitive functions in a way that puts these people at greater risk for dementia and Alzheimer's down the line. Either way, says Hakansson, the results suggest that "if you are looking for interventions to prevent Alzheimer's, one way may be to identify people who have been divorced or widowed, and who haven't adapted or gotten back into the social circle, and give them support with the aim of giving them new structure and social networks in their lives."

As more discoveries are made, researchers hope they'll develop a better understanding of who is most at risk of Alzheimer's disease, how each patient's case is unique, and how best to treat specific patients with the drug and lifestyle changes that will be most effective for them. Taken together, these approaches could one day make the long goodbye of Alzheimer's a thing of the past.