SLU Studies Drug for Early Stages of Illness

Researchers at Saint Louis University are studying a drug for patients who show early signs of Alzheimer’s disease as a part of a multi-center trial being held at nearly 70 centers in North America and Europe. The medication is being tested for safety, tolerability and efficacy, with the hope that it may help ward off the debilitating illness.

“By learning more about the early stages of the illness, we may be able to delay or prevent full Alzheimer’s,” said George Grossberg, M.D., director of geriatric psychiatry and principal investigator for the study at Saint Louis University School of Medicine. “With this study, we want to know if a medication can help people who may be having a few senior moments, before those issues develop into daily memory problems that affect their ability to function on a regular basis.”

Approximately 5.3 million adults in the U.S. suffer from Alzheimer’s disease, and the number of cases is expected to double by 2050. The neurodegenerative illness begins with memory loss and progresses to severe cognitive impairment, altered behavior and decreased motor function.

Researchers are studying the earliest phase of the illness, called prodromal Alzheimer’s disease. During this stage, patients may experience memory loss or mild cognitive impairment.

Recent studies suggest that early Alzheimer’s disease can be detected with biomarkers in spinal fluid. Using this information, researchers hope to alter the course of the illness by treating it early. There is no current drug therapy for prodromal Alzheimer’s disease.

Investigators will test an investigational medication, BMS-708163, a drug researchers hope may hinder enzymes that form damaging beta-amyloid plaques, which are linked to Alzheimer’s disease.

World-wide, around 270 patients will be enrolled in the study. All patients will be randomly assigned to receive either the study drug or a placebo.

Researchers are enrolling patients in the study between the ages of 45 and 90 who have symptoms suggestive of early stages of Alzheimer’s disease, such as memory complaints or mild cognitive impairment. Participants will undergo testing of their cerebrospinal fluid to confirm changes suggestive of Alzheimer’s disease.

Study participants may continue taking certain, study-approved prescription medications they are currently taking for Alzheimer’s disease if they have been on a stable dose for at least three months. Participants must be accompanied by a reliable study partner with whom they spend at least 5 hours per week.

For more information about the study, call (314) 977-4900.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

SOURCE: www.slu.edu

Datamonitor — A Phase III trial evaluating Medivation/Pfizer’s Dimebon in Alzheimer’s disease has failed to meet any of its clinical endpoints, despite high hopes of the drug after promising Phase II results. This is a significant setback for Dimebon’s developers, particularly Medivation, but hope for the millions of Alzheimer’s sufferers and their caregivers remains in the pipeline.

CONNECTION fails to validate positive Phase II results

On March 3, Medivation announced that its big hope for Alzheimer’s disease, Dimebon (latrepirdine; Pfizer), failed to achieve clinical benefit over placebo in one of its pivotal Phase III trials. In the trial, dubbed the CONNECTION study by the company, investigators were unable to demonstrate that Dimebon significantly slowed the progression of the disease based on any of the five commonly used endpoints. Speaking in a press conference, Medivation/’s CEO David Hung stated: “The outcome of the trial was unexpected, and is obviously a major disappointment, especially for Alzheimer’s patients and their caregivers.”

The result certainly comes as a surprise to those tracking the progress of the drug. The CONNECTION data stand in stark contrast with positive Phase II results released in 2006, which served to greatly raise expectations of what was purported to be a future blockbuster for Alzheimer’s disease. Indeed, on the strength of these data, Datamonitor had previously forecast Dimebon to achieve annual sales of around $5 billion in the seven major markets by 2018, placing it as one of the biggest-selling drugs at this time.

Early analysis of the CONNECTION data suggests that the placebo response was greater than that previously seen and that Dimebon showed ‘a materially weaker response’. The study results, drawn from 598 participants across the US, Europe and Latin America, contradict those from the preceding Phase II trial, which involved 183 patients in Russia. These Phase II data were so encouraging that they were published in the July 2008 issue of the Lancet.

However, even before the CONNECTION data were revealed, some experts interviewed by Datamonitor were skeptical of the outcome of the Russian trial. In its press announcement for the Phase III trial, Medivation conceded that the Russian results may have been limited by the small sample size, the involvement of just one geographical location and the use of only one language to communicate disease severity. Nevertheless, many more remained highly encouraged by the Phase II data and regarded Dimebon as one of the most promising candidates in late-stage development for Alzheimer’s disease. Indeed, >/Pfizer’s decision to in-license the drug at such a high cost is testimony to these high hopes.

Medivation will face a rough patch, though it is not yet over for Dimebon

Medivation has suffered as a result of Dimebon’s failure, with its share price plummeting by 68% to $13.04 from an all-time high of $40.49 only the day before the announcement. With future milestone payments and royalties hanging in the balance and no products currently on the market, Medivation has undoubtedly suffered a major blow. However, although the CONNECTION results are certainly a setback, they do not necessarily spell the end for Dimebon. Datamonitor expects that the company will now pin its hopes on longer-term Alzheimer’s trials already underway as well as Dimebon’s secondary indication in Huntington’s disease, for which it is currently in Phase III development.

Pfizer, which signed a collaboration deal with Medivation in September 2008 and has since co-developed the drug, stands to lose most or all of the return on its large investment. The company’s initial upfront payment to Medivation was $225m, one of the largest of its type in recent years. Still, the CONNECTION setback is mediated somewhat by Pfizer’s existing presence in the Alzheimer’s marketplace, through its market-leading compound Aricept (donepezil) and the extensive portfolio of pipeline candidates which it inherited following the acquisition of Wyeth.

One positive to come out of the failure is that there will not be significant ramifications for other drugs in development for Alzheimer’s disease. Within the current pipeline, Dimebon is unique in its mode of action. The drug is a small molecule mitochondrial permeability transition pore (MPTP) blocker, as well as an NMDA receptor antagonist and cholinesterase inhibitor. Unlike Dimebon, the majority of the other pipeline candidates are targeted towards the hypothesized Alzheimer’s disease etiology. Drug developers’ focus has shifted from neurotransmitter replacements to biological agents that affect beta-amyloid and tau protein, both hallmarks of the disease. The next eagerly awaited compound for which Phase III results will be announced is likely to be bapineuzumab (Johnson & Johnson/Pfizer), a humanized monoclonal antibody for beta-amyloid. However, given the high attrition rate in the pipeline, expectations will be tempered.

As other markets stall, the high risk/high reward of Alzheimer’s is tempting.

There remains an enormous unmet need in the treatment of Alzheimer’s disease. For the millions of elderly people worldwide, there are just four drugs available to them that can only offer a modest symptomatic effect. Even so, these treatments cannot slow or modify the course of this neurodegenerative disease, which is the ultimate goal in Alzheimer’s therapy. However, despite this need, drug developers have struggled to get new agents to market and the pipeline over the past 10 years is littered with late-stage failures. Indeed, excluding reformulations, no new drugs have launched for Alzheimer’s disease since Namenda (memantine; Forest/Merz/Lundbeck) arrived in 2002. Since then, around 20 products have failed Phase III trials.

With this in mind, then, the news about Dimebon may not be such a surprise after all. It is, of course, a big disappointment to those in the Alzheimer’s community, but the future looks bright. As other core therapy markets become less profitable, both major pharmaceutical and biotech firms are increasingly looking to the huge potential of the untapped Alzheimer’s disease market. Investment into Alzheimer’s drug R&D continues to grow exponentially and, ultimately, this is the best news for sufferers: it is only a matter of time before an effective therapy arrives.

SOURCE: www.biospace.com

Today was an important day in the development of clinical trials for investigational drugs to treat mild-to-moderate Alzheimer’s Disease (AD). Pfizer/Medivation announced this morning the failure of their Phase III clinical trial of the investigational drug Dimebon. (For those who missed the news, see the story): Click Here

Although the announcement was not surprising to Curaxis Management or its scientists, it nonetheless is a difficult outcome for those suffering with this disease, and the families that care for and love them. Curaxis Pharma is dedicated to providing meaningful treatments for diseases of aging, including AD, and empathizes with the horrendous plight these families experience and the hope they hold onto for help.

We believe, as we did at the outset, that the data provided on this drug was flawed. Medivation in-licensed Dimebon, which is an antihistamine used in Russia for many years, from a Russian neuroscientist several years ago. Medivation then sponsored a Phase II study in Russia to determine effectiveness. The results of this study were very strong – so good in fact that their data showed results never before seen in any AD trial. Obviously, the scientific community was taken by surprise, and many wondered about the integrity of the Phase II trial and the related data.

Another major issue from Curaxis’ viewpoint was the lack of any consistent explanation of Dimebon’s method of action. Medivation could not really define how Dimebon worked and over time suggested a series of different possible methods of action. This seemed like a red flag to us.

Late last year Pfizer announced the drug Dimebon increased Beta Amyloid in the treated group. This seemed like yet another red flag, as most AD drugs in development seek to lower Beta Amyloid to treat AD.

The bottom line is that the failed Phase III trial of Dimebon, which was conducted at clinical sites in the United States and other countries, completely failed to duplicate the results achieved in the Phase II trial conducted in Russia and by a wide margin. Indeed, the results in the Phase III trial demonstrate absolutely no benefit for the group treated with Dimebon versus the placebo group. The doubts of the skeptics certainly seem validated.

Unfortunately for the families of those afflicted with AD, we do not believe subsequent trials for Dimebon will result in any different outcome. We believed from the beginning that the science was flawed and these results were the only inevitable conclusion.

What does this mean for Curaxis? As we have stated, the race to solve the challenge of AD remains wide open. It is a challenging and complex field with very few answers at this point. We believe that our product candidate, Memryte®, addresses each of the pathways through which the pathology of AD develops. We give some more detailed information in our video presentation and on our website, but suffice it to say that the evidence we have gathered to date is good enough to warrant taking our product into a Phase II trial of Memryte in women with mild-to-moderate AD planned for later this year.

In the field of complex and expensive medical research, there will always be failures. They are a necessary by-product of the ultimate success that we are convinced will come with a treatment for Alzheimer’s. We are on the path to combat this disease and to bringing a new and meaningful treatment to market for those suffering with AD.

Patrick Smith, Chairman and CEO

By LINDA A. JOHNSON (AP) – 5 hours ago

TRENTON, N.J. — A promising Alzheimer’s disease drug Pfizer Inc. and a partner are developing failed to work in a late-stage study, a startling disappointment after the potential blockbuster kept symptoms from worsening for a year in a prior test.

Pfizer and partner Medivation Inc. said Wednesday that the experimental drug, Dimebon, failed to meet its primary and secondary goals — improving thinking ability and overall daily function over six months in patients with mild to moderate Alzheimer’s disease.

Still, the results don’t necessarily spell the end for Dimebon, one of New York-based Pfizer’s key prospects. Medivation and Pfizer, the world’s biggest drugmaker by revenue, are continuing three studies that could prove Dimebon helps patients in combination with other Alzheimer’s drugs or when used for a longer period.

Given strong results of the prior, midstage study, some doctors thought — or at least hoped — Dimebon might be able to stop or reverse the mind-robbing disease, which would be a first.

“It’s a setback, because it was the drug nearest to approval,” said Dr. Ronald Petersen, chairman of the Alzheimer’s Association’s medical and scientific advisory council. He said it could have been on the market in two years, and anything else will take much longer.

The news drove down shares of Medivation and Pfizer.

Still, Petersen said the result is “not a death knell,” as the other Dimebon studies continue.

Dr. Lynn Seely, chief medical officer of San Francisco-based Medivation, said, “The battle did not go well, but the war isn’t over.”

The four existing drugs can only temporarily reduce symptoms: memory problems, confusion, aggression and a general decline in ability to function. The newest one, Namenda, was approved in 2003. The leader is heavily advertised Aricept, sold jointly by Pfizer and Japan’s Esai Co. Ltd., with about $3.7 billion in sales last year.

“It is a short-lived, finite benefit, a year, two years, somewhere in that ballpark,” that these drugs reduce symptoms, Petersen said.

Already, about 5.3 million Americans have Alzheimer’s disease and by 2050, up to 16 million may have it, according to the Alzheimer’s Association. The disease strikes nearly a half million new patients a year, mainly as people hit their 70s or 80s.

“The baby boomers are just getting there now, so that’s why it’s so crucial that we find something now,” said Petersen, who heads Alzheimer’s research at the Mayo Clinic.

Dimebon was expected to at least lessen symptoms more than the existing drugs, though its full potential was unclear because its mechanism of action is not entirely understood.

It works differently than the four Alzheimer’s drugs already on the market, which act on particular chemicals in the brain to improve nerve cell function. So Dimebon could have been used along with any one of those to ease symptoms even more.

Either way, Dimebon was seen as a probable blockbuster, given the desirability of any drug that can delay worsening of symptoms — and the need for expensive nursing home care.

Yet in the final-stage study, which included 598 patients with an average age of 74, symptoms didn’t subside in either patients getting Dimebon or those getting dummy pills.

“We believed that this drug would improve the symptoms of Alzheimer’s disease, as well as stabilize the symptoms over time,” said Seely. “We are very surprised by these results and (are) analyzing the data, trying to understand what went wrong.”

Petersen said there are 90 to 100 other drugs in various stages of testing at drug companies and universities around the world, but this failure comes at a bad time, given the disease’s increasing prevalence and the recession-related decline in government and foundation funding for Alzheimer’s research.

One analysts are closely watching is bapenuzemab, a drug in late-stage testing being developed under a partnership of Pfizer and a Johnson & Johnson unit.

Analyst Steve Brozak of WBB Securities said failures of drugs in final patient testing aren’t that rare, but it is “unusual in something that they have such high hopes for.”

“Nobody was going out there and saying, ‘This would be the be-all and end-all,’” he added.

Seely noted experimental drugs sometimes fail in one study but produce good results in others and ultimately are approved, as happened with Namenda.

The two companies are testing Dimebon, known chemically as latrepirdine, in three additional studies involving patients with moderate to severe Alzheimer’s, and in one involving patients with Huntington’s disease. That’s a fatal genetic disorder that causes muscle twitches and eventual deterioration in mental abilities.

Under their 2 1/2-year-old partnership, if Dimebon is approved, Medivation would get hundreds of millions in milestone payments, plus royalties on its sales.

Medivation shares plunged $27.15, or 67 percent, to close at $13.10. Pfizer shares fell 28 cents to $17.32.

SOURCE: The Associated Press

By Elizabeth Allen – Express-News

Rapamycin, which drew attention last summer for extending the lives of mice, now is showing promise in treating mice with the mouse equivalent of Alzheimer’s.

Mice with human genes that developed Alzheimer’s symptoms were able to learn and remember as well as normal mice when fed the drug, according to a University of Texas Health Science Center study published Feb. 23 in the Journal of Biological Chemistry.

The new study, led by physiology Professor Salvatore Oddo, is one of nine offshoots from a study that extended the lives of female mice by 14 percent and of males by 9 percent. Those results, produced by the health science center’s Barshop Institute for Longevity and Aging Studies and two other labs, were published in July in the journal Nature.

The normal mouse life span is up to 24 months. The experiment began when the mice were 6 months old, just beginning to develop the lesions associated with Alzheimer’s, Oddo said.

The 57 mice were drilled four times a day, five days a week, on learning and memory. Researchers used a mouse-sized heated swimming pool with a small platform in part of it, just below the surface where the mice couldn’t see it. They then placed a couple of visual cues around the pool to help the mice orient themselves.

Since mice don’t like water, even warm water, they swam around looking for a way out until they bumped into the platform. After the mice climbed up on it, researchers left them there a few seconds to look around and see the visual cues before plucking them out and warming them on a heating pad.

“We try to keep the stress as low as possible, because that may alter the results,” Oddo said.

After four or five days of drills, normal mice swam straight to the platform. The mice with the Alzheimer’s-like brains that were given rapamycin did as well as the normal mice, Oddo said, reversing the Alzheimer’s-like effects.

The normal mice that were given rapamycin, however, did no better than the normal mice that had none, Oddo said.

After that, “we sacrifice the mice and we take their brains out,” Oddo said. Brains of the transgenic mice that ate rapamycin had fewer and smaller lesions than the transgenic mice that had none.

What that may mean for humans will require further research.

“A mouse is a mouse, of course,” Oddo said. “How much you can extrapolate that to humans depends on who you talk to.”

Alzheimer’s advocates also warned that the results are preliminary.

Whenever a new study hits the news, relatives of Alzheimer’s patients start calling, said Ginny Funk, spokeswoman for the regional chapter of the Alzheimer’s Association.

“We know that truly the only thing that is going to stop this dreadful disease is research,” Funk said, “but we also have to explain to families that it can also take a long time.”

Oddo has launched his next study, raising 80 mice to the age of 15 months, when the Alzheimer’s-like symptoms would be more advanced, and researchers will try to understand exactly how the rapamycin helps the mouse brain.

Rapamycin, which was originally discovered in soil from Easter Island, is used as an immune-suppression drug to help people’s bodies accept organ transplants. The original Barshop Institute longevity study, led by molecular medicine Professor Dave Sharp and pharmacology Professor Randy Strong, was listed as a runner-up for “breakthrough of the year” by Science Magazine and garnered the health science center a $5.2 million federal stimulus grant to fund a cascade of follow-up studies on rapamycin.

SOURCE: mysanantonio.com

Researchers Link Elevated Level of Protein to Memory Loss, Decreased Gray Matter

(CBS) Researchers have found that elevated levels of a damaged protein in the brain may be an early marker for Alzheimer’s disease in healthy adults.

Phosphorylated tau231 (P-tau231) is a damaged tau protein found in patients with Alzheimer’s disease. The study, conducted by researchers at NYU School of Medicine and published in this month’s Neurobiology of Aging, shows that the presence of the protein can predict future memory decline as well as a loss of brain gray matter in the medial temporal lobe – a key memory center in the brain.

Other studies have shown that in Alzheimer’s disease, tangles of damaged tau proteins gather in the medial temporal lobe.

“Our findings suggest that P-tau231 has the potential to be an important diagnostic tool in the pre-symptomatic stages of Alzheimer’s disease,” said lead author Dr. Lidia Glodzik, an assistant research professor at the Department of Psychiatry at the Center for Brain Health and Center of Excellence on Brain Aging at NYU School of Medicine.

Researchers followed 57 healthy older adults and looked at memory performance and gray matter using MRI scans. Two years later, 20 of the subjects had worsened memory and more atrophy in the medial temporal lobe, as well as higher baseline levels of P-tau231.

“Indentifying people at risk for Alzheimer’s disease is the necessary first step in developing preventive therapies,” said co-author Mony de Leon, a professor at the Department of Psychiatry and director of the Center for Brain Health at the Center of Excellence on Brain Aging at NYU School of Medicine and Research Scientist at the Nathan S. Kline Institute for Psychiatric Research. “This study shows that Alzheimer’s disease pathology may be recognized in the normal stages of cognition. This observation may be of value in future studies investigating mechanisms that cause or accelerate dementia.”

SOURCE: CBS News

A study initiated by the University of Michigan Health System revealed that lack of adequate vision coverage of older adults may render them at increased vulnerability of Alzheimer’s disease – the most common form of dementia.

The study appears online ahead of print in the American Journal of Epidemiology.

Scientists scanned people’s brains to depict that hypertension add to a kind of scarring which later results in the development of Alzheimer’s disease and other dementias. Those scars can start building up in middle age, decades before memory problems will appear.

The study, which used Medicare data, reflected that those suffering with inadequate vision who visited an ophthalmologist at least once for an examination were 64 per cent less prone to develop dementia.

“Visual problems can have serious consequences and are very common among the elderly, but many of them are not seeking treatment”, says lead author Mary A. M. Rogers, Ph. D.

To reach the conclusion, Rogers and her colleague Kenneth M. Langa, M. D., Ph. D., professor of internal medicine at U-M Medical School, is reported to have analyzed information from the nationally representative Health and Retir.

SOURCE: topnews.us

AAP

Australian scientists have isolated a cause of poor memory in otherwise healthy older men. It relates to elevated levels of a particular sex hormone.

Luteinising hormone (LH), which is produced by the pituitary gland, controls the release of testosterone and men with higher levels of it were shown to perform poorer on memory tests.

The finding has implications for the search for a treatment for Alzheimer’s disease, says lead researcher Zoe Hyde.

While previous studies had found elevated LH levels in men with Alzheimer’s disease, her research was the first to find the effect also in healthy men.

“We know that testosterone acts on the brain in a number of ways but LH was thought to have no direct effect,” says Ms Hyde, from the Western Australian Centre for Health and Ageing.

“This study provides new insight into how hormones affect the brain and reveals a potential target for Alzheimer’s disease drug therapies.

“However, more work is required before we can fully understand the role that LH plays in the brain.”

The memory curbing effects of LH was independent of an older man’s testosterone levels.

LH also controls the release of oestrogen in women.

Ms Hyde’s research was conducted as part of the major Health in Men Study, which has followed a group of 12,000 men aged 65 and over since 1996.

It is the largest study of ageing men in Australia, funded by the National Health and Medical Research Council of Australia (NHMRC).

The research is published in this month’s issue of the Journal of Alzheimer’s Disease.

SOURCE: AAP (Australian Associated Press)

Curaxis Pharmaceutical Corp. is committed to providing the latest information on Alzheimer’s Disease. In an effort to help inform and educate, we’ve produced a five-minute video detailing the disease and our encouraging research that we believe may result in a significant treatment for AD.

The video includes a general overview of current state of the disease; how it affects our society as well its development and the relationship between the HPG Axis and the human growth cycle. This explains the platform for our science and how our research may offer hope to the millions of lives affected by AD.

We hope that you find this video insightful and useful. Please share it with friends and loved ones who are affected by the disease so that they may gain a better understanding of our unique approach.

We remind you to check back often for Alzheimer’s Research updates from the Curaxis Team!

Note: The video requires Flash in order to view. Please check to see that your Flash player is up to date for best results.

VANCOUVER, British Columbia, Feb. 10 (UPI) — Canadian researchers say their findings challenge the idea marijuana tempers Alzheimer’s disease.

Researchers at the University of British Columbia in Vancouver found the treated mice had just as much plaque formation and the same density of neurons as the control group. However, the group given higher doses actually had fewer brain cells.

“As scientists, we begin every study hoping to be able to confirm beneficial effects of potential therapies, and we hoped to confirm this for the use of medical marijuana in treating Alzheimer’s disease, but we didn’t see any benefit at all,” study leader Dr. Weihong Song said Monday in statement. “Instead, our study pointed to some detrimental effects.”

Song and colleagues used mice carrying human genetic mutations that cause Alzheimer’s disease, considered to be a good model for the disease in humans. Over a period of several weeks, some of the Alzheimer’s-afflicted mice were given varying doses of HU210 — the synthetic and much more potent form of compounds in marijuana known as cannabinoids thought to fight the formation of plaques in the brains of Alzheimer’s victims. Their memory was then tested.

“Our study shows that HU210 has no biological or behavioral effect on the established Alzheimer’s disease model,” Song said.

The study was published in Current Alzheimer’s Research.

SOURCE: www.upi.com