Chemical castration as treatment for Alzheimer's?

[Eunuchist (imported)]

Prostate cancer drug may help Alzheimers patients

Dec 28, 2005 08:56 PM

We live in a day and age where there are a growing number of options for the treatment of the mind-robbing disease known as Alzheimer's.

One of the latest being studied is also approved to treat prostate cancer.

Barbara Morse-Silva reports.

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Maria and Robert Digiuseppe have been married for 52 years. Each memory, each occasion very special to this couple.

"We just had a grandchild after 52 years." and Maria is hoping to hold on to these cherished moments for as long as she can.

You see, a few years ago, she was diagnosed with Alzheimer's.

Robert Digiuseppe says, "It's a tough ordeal."

That's why this couple is willing to try a new treatment that may help slow, even stop the progression of her disease.

It's currently being used to treat prostate cancer.

Dr. Stephen Salloway, Alzheimer's researcher, says, "The way this treatment was discovered is a patient with Alzheimer's disease who developed prostate cancer received this medicine called "Lupr", another name is Lupron, and his family noticed that the Alzheimer's disease seemed to arrest itself."

Earlier clinical trials using Lupron on Alzheimer's patients showed it stabilized the disease, in other words, patients taking it didn't get any worse.

But it was given in injection form.

Now, they're trying another delivery method: a tiny tube loaded with the medicine. It's inserted just under the skin in the abdomen.

Dr. Salloway says, "...and it slowly releases over a period of eight weeks. You get a better delivery of medicine over that eight weeks than giving it by injection. When you give it by injection, your blood level goes up and then it goes down and it's gone. When you give it this way, it's slow release and it's more available to the body to work so it works over a longer period of time."

The Digiuseppes are hoping this treatment works, especially Robert who's taken on a lot of the household chores.

Robert: "Do the laundry, do the cooking."

Maria: "He's taken over."

Robert: "She'll do anything to avoid that."

Maria: "Ahhhh, so you have an ulterior motive."

Robert: "Yes."

The study is ongoing, so it will be some time until complete results are compiled.

http://www.kvoa.com/Global/story.asp?S= ... =menu216_8

[Eunuchist (imported)]

A few more follow-up articles on the story:

Shocking, but potentially promising way to treat Alzheimer's - Lupron

July 22nd 2006

Lupron

For the last several years, the main drug used to treat Alzheimer's disease has been Aricept, but its benefit isn't long-lasting, spanning maybe 18 months to 2 years. Yet surprisingly, a randomized study out just this week has added another clue to the mystery of this tragic disease - a drug called leuprolide (brand name Lupron) commonly used to treat prostate cancer, breast cancer, and endometriosis was found, after 12-48 weeks, to significantly slow the progression of Alzheimer's.

Lupron's mechanism of action is that it blocks LH (luteinizing hormone), which prompts the pituitary gland to produce gonadotropins, hormones that stimulate the ovaries and testes to produce the high levels of estrogen and testosterone necessary for reproduction.

This drug is given as a shot and helps to treat recurrent fibroids or endometriosis and is used as a way to induce temporary menopause in early and late stage breast cancer patients; it also shuts down testosterone production in men with prostate cancer.

The baffling thing about this new, yet inconclusive, Alzheimer's study to some scientists is how this observed benefit could possibly be real, since this is a drug that blocks the "brain protective" hormones estrogen and testosterone. However, if researchers are truly following all of the current, available evidence surrounding hormones' effects on cognition, this study should NOT be a surprise! In fact, a lot of valid scientific evidence points to the contrary, that excessively high levels of reproductive hormones throughout life may be bad for the brain.

The most conclusive data to date, at least in women, comes from (yet again) the WHI (Women's Health Initiative) which surprised everyone when the trials found stroke and memory risks (including dementia) for women on estrogen or estrogen/progestin. While this study may have been a shock, there were other observational data out years before this study that spelled trouble. The Rotterdam study, for example, evaluated the natural estradiol levels of older women to see if there was any association with cognition. Surprisingly, the women with the highest levels had a doubled incidence of vascular dementia and a slightly greater risk of Alzheimer's.

In April 2000, another study conducted by Terry Manolio of the National Heart Lung and Blood Institute, looked at the MRIs of the brains of 2000 women, half of whom were taking estrogen. Again, the estrogen users' brain scans showed slightly more decay than the non-users. Dr. Manolio herself didn't know what to make of this and worried that this would scare women off of their hormone replacement since it was basically a given that the therapy was beneficial! Also, a laboratory study out of Emory that went virtually unnoticed involved sophisticated cognitive tests of older female cynamalgous monkeys who either retained their ovaries or had them removed at a young age.

This study, according to the scientists, actually found a PROTECTIVE effect of ovary removal on spatial-visual memory in the older monkeys. And lastly, a small study out from Urbana-Illinois, reported this Janurary, showed that high levels of fitness counteracted the cognitive decline associated with longterm HRT use. Again using brain MRIs of 54 women, this study found that those who used HRT for 10+ years had decreases in the 4 different areas of gray matter in the brain, but that exercise lessened these decreases. While only the WHI is truly definitive out of all these studies, it seems clear that hormones do not have any preservative effects on thinking and cognitive abilities.

Based on this data, hormonal decline with age should no longer be viewed as a bad thing, but rather a natural protective mechanism. Secondly, attempting to replace hormones is fraught with multiple hazards. Third, the healthiest lifestyles are those which actually lessen the effects of reproductive hormones on the body's organ systems. Obesity, which is a risk factor for heart disease, colon and reproductive cancers, and probably dementia, is a condition involving excessive estrogens and androgens.

Exercise and a diet than keeps weight down have long been known to be beneficial, although the precise mechanisms haven't been clearly pinpointed. Hypothetically, it may be a hormone lowering effect. Taking all of this into account, it seems that scientists should have enough basis to be pooling their efforts into exploring the effects of hormonal manipulation as a way to prevent/treat Alzheimer's, stroke, and other serious brain degenerating diseases.

A word of caution in all this - to espouse the widespread, longterm use of drugs that BLOCK hormones (be it Lupron or whatever else comes along) is just as bad an idea as HRT was!! Both are clearly disrespectful toward the natural intricacies of human biology. Instead, a more accurate interpretation (at least in terms of this latest Alzheimer's research) is that both menopause in women and the natural age related androgen decline in men do not trigger the aging process but are instead inherent natural processes that PROTECT us from diseases. And Alzheimer's, perhaps the scariest of all, might just be one of them. We now know that hormones don't need replacing. And we also have good reason, at least from a hormonal standpoint, to be espousing widespread modalities aimed to lessen the overweight epidemic in this country, considering all of the various other diseases associated with it. Conclusive answers are not yet in, but the puzzle is certainly coming together.

http://bestsyndication.com/Articles/200 ... s_hope.htm

[Eunuchist (imported)]

Several drugs show promise for alzheimer's

Tuesday, October 17, 2006

By Elena Cherney, The Wall Street Journal

Scientists are exploring several promising avenues in drug research that could strengthen the battery of weapons used to slow the scourge of Alzheimer's disease.

A handful of drugs -- some originally approved for other diseases -- are showing some success in clinical trials at slowing the cognitive decline that is the hallmark of Alzheimer's. A few, including a prostate-cancer drug, a diabetes drug and a medicine derived from an old class of anti-inflammatory drugs, are in late-stage trials. Their makers say they expect to seek regulatory approval for the treatment of Alzheimer's within a few years. Other compounds, including cholesterol-lowering statins and antibodies that bolster the immune response against the disease, are also showing promise.

If approved for Alzheimer's, the drugs could be a huge breakthrough because they seek to modify the brain processes that cause Alzheimer's, even though those processes aren't fully understood. In contrast, none of the currently approved medicines attack the underlying mechanisms of the disease, offering only limited relief from some symptoms. The four drugs currently approved for Alzheimer's -- Aricept, Exelon, Razadyne and Namenda -- are a huge business. Alone, sales of Aricept, co-marketed in the U.S. by Pfizer Inc. and Eisai Inc., totaled $1.06 billion in the year ended March 31. But typically, patients gain only modest cognitive improvement for less than 18 months. Then, they start to deteriorate again.

Many leading researchers say they believe at least some of the drugs being studied are likely to win approval for Alzheimer's. "I can't promise," says Sam Gandy, director of the Farber Institute for Neurosciences at Thomas Jefferson University. But "there could be compounds in as few as three years."

In the meantime, a growing number of doctors are experimenting with new ways to use existing Alzheimer's drugs. In particular, doctors are giving medications such as Aricept earlier in the course of the illness -- often before patients are even sick enough to be diagnosed with Alzheimer's. Recent studies of patients with so-called mild cognitive impairment, which involves loss of mental function and sometimes progresses to include dementia and full-blown Alzheimer's, have turned up some evidence that the deterioration into Alzheimer's could be delayed by starting treatment.

The need for better treatments has never been more pressing, as the first members of the Baby Boom generation reach their 60s, the age at which the risk of developing Alzheimer's starts to climb. An estimated 4.5 million Americans have the disease, more than double the 1980 number, according to the Alzheimer's Association.

Here is a look at some of the emerging trends in Alzheimer's research:

Existing Alzheimer's Drugs

Wayne Lindley, an 83-year-old North Carolina retiree, started to notice a few years ago that he was having trouble remembering how to perform certain computer functions for his part-time record-keeping job. When Mr. Lindley and his wife, Sarah, consulted an Alzheimer's specialist last year, Mrs. Lindley says, "his opinion was, you don't have Alzheimer's but I'm going to put you on Aricept."

Mr. Lindley is among those people showing early signs of Alzheimer's who are taking approved Alzheimer's drugs before a firm diagnosis. Despite recent evidence that early treatment with Alzheimer's drugs can stave off cognitive decline, Mr. Lindley says he hasn't noticed any improvement: "The other day, I looked at all the pills and wondered, do I still need all these things?" he says. Still, he says he will continue participating in a neuroimaging study at Duke University in which his doctor enrolled him, and he hopes that tests he is undergoing will give his family more information about his prognosis. "I don't want to be in the dark about anything," he says.

Researchers caution that patients with mild cognitive impairment should think carefully before starting on Alzheimer's medication before there is a diagnosis. The drugs can have side effects ranging from mild nausea to stomach bleeding. Some neurologists consider mild cognitive impairment to be early-stage Alzheimer's if it is progressive and not caused by a different health problem, but the condition doesn't necessarily progress to Alzheimer's.

Nevertheless, "over the last year or so, we've seen a dramatic increase in the number of people who don't yet meet the criteria for Alzheimer's and are coming in on medication already," says Gregory Jicha, an assistant professor of neurology at the Alzheimer's Disease Center at the University of Kentucky.

Drugs for Other Conditions

Most researchers say a protein called beta-amyloid is at the root of Alzheimer's. The protein appears to build up into plaques in the brain and progressively kill neurons, or nerve cells, in a process known as the "amyloid cascade." Many of the drugs being studied aim to interrupt this cascade.

Some of the most promising results to date involve Flurizan, which is derived from an anti-inflammatory and is being tested by Myriad Technologies. The drug targets an enzyme, called gamma secretase, that is believed to play a role in the build-up of amyloid. The company is scheduled to finish its final U.S. study in the spring of 2008, and hopes to apply to the Food and Drug Administration that summer, says Executive Vice President Bill Hockett.

Some researchers think that the best approach may turn out to be a cocktail of different compounds. Different drugs may also work better for different patients, depending on gender and genetics. For example, leuprolide, the prostate-cancer drug that is being tested in Alzheimer's patients by Voyager Pharmaceuticals Inc. of Raleigh, N.C., has appeared more effective in women than in men. Leuprolide, approved as Lupron for prostate cancer, targets luteinizing hormone, a pituitary hormone believed to promote the production of beta-amyloid.

In a study of 50 women presented this summer in Madrid, women with mild to moderate Alzheimer's disease who took the drug for 48 weeks saw a dramatic slowing of their deterioration, compared with women who didn't get the drug. "The men's study was not as compelling," says Brian Reynolds, Voyager's director of medical information. That could be in part because while luteinizing hormone increases dramatically in women after menopause, its increase is more gradual in men. A Phase III trial will wrap up next fall, Mr. Reynolds says, and the company hopes to have data by early 2008 to prepare an application to the FDA.

Patient responses to a form of the GlaxoSmithKline diabetes drug Avandia suggest that genetics may play a part in determining treatment. In an earlier trial of the drug involving 511 people, patients with a gene that made them more susceptible to Alzheimer's didn't benefit, while those lacking the gene showed improvement. The diabetes drug is believed to play a role in how brain cells metabolize glucose, a process that GlaxoSmithKline researcher Allen Roses believes will eventually prove to be the culprit in Alzheimer's. Dr. Roses says he is "optimistic" that Phase III trials now getting under way will pave the way for approval of the drug for Alzheimer's. Those trials will enroll about 2,800 patients in the U.S. and 32 other countries, according to a Glaxo spokesman.

Cholesterol-lowering statin drugs are also showing some promise. Through the National Institute on Aging, the NIH has funded a recently completed study to test whether the statin Zocor, from Merck & Co., can stall Alzheimer's in patients with normal cholesterol levels. "The idea is that lipid lowering seems to also lower the amount of amyloid in the brain," says Mary Sano, director of the Alzheimer's Disease Research Center at Mount Sinai Hospital in New York. In addition, Pfizer is recruiting patients for a study of Lipitor in Alzheimer's patients.

A note of caution: While these drugs are already on the market for other conditions, doctors and researchers say it would be unwise to prescribe or use any medicines "off-label" for Alzheimer's. The patients who are taking them now are in the controlled environment of a clinical trial with heavy oversight, researchers note, and problems could still crop up, even during the last rounds of testing.

New Drugs

Researchers also tout Alzhemed, a drug being developed by a Canadian company, Neurochem Inc., in a Montreal suburb. In an earlier study, patients with mild Alzheimer's remained stable for 20 months. Some patients who participated in an extended study have been getting the medication for three years and "have stayed the same," says spokeswoman Lise Hebert.

Some researchers are looking at ways to stimulate the immune system to fight the disease. Researchers at Eli Lilly & Co. are in the early stages of trials of an antibody that binds to beta-amyloid and prevents it from building up. That study is still recruiting patients. Lilly investigators are further along in trials of a drug that moderates the activity of an enzyme that appears to promote the production of amyloid, says company researcher Eric Siemers. Also, Wyeth, Madison, N.J., is working with Elan Pharmaceuticals Inc. to develop an injectable protein that would prevent the build-up of beta amyloid.

http://www.post-gazette.com/pg/06290/730724-114.stm

[Eunuchist (imported)]

Novel Approach May Offer New Hope To Women With Alzheimer's Disease, Study Shows

Leuprolide acetate helps women with mild-to-moderate Alzheimer's disease maintain functional capabilities for a longer period of time, according to data presented Monday by Voyager Pharmaceutical Corporation.

The company shared its findings from a Phase II clinical trial in women at a symposium held during the 10th International Conference on Alzheimer's Disease and Related Disorders, presented by the Alzheimer's Association. This report expanded on the Phase II data presented in Geneva, Switzerland in April by Dr. Brian Reynolds, director of medical and scientific information for Voyager.

"Women treated with leuprolide acetate and the current standard of care, acetylcholinesterase inhibitors, better maintained their level of cognitive ability and daily activities for nearly one year," said Dr. Christopher Gregory, vice president of research at Voyager. "These findings mean that, for a sustained period of time, women treated with the drug were able to maintain their memory and their ability to do things like dress themselves."

The findings resulted from a subgroup analysis of VP-AD-103, Voyager's clinical trial testing the efficacy and safety of leuprolide acetate in women with mild-to-moderate Alzheimer's disease. The trial was a 48-week, double-blind, placebo-controlled study observing women age 65 and older.

The subgroup analysis compared two groups of women with mild-to-moderate Alzheimer's disease. The first group consisted of women treated with leuprolide acetate and acetylcholinesterase inhibitors (AChEIs). The second group consisted of women treated with placebo and AChEIs.

Women in the study were assessed on three measures: cognitive ability (measured by an assessment known as ADAS-Cog), clinical impression (a physician and caregiver assessment known as ADCS-CGIC), and ability to perform daily activities (as assessed by the caregiver on a scale known as ADCS-ADL). The treatment group performed significantly better than the placebo group on all three measures.

Nearly 90 percent of the eligible women from the Phase II trial elected to participate in an open-label extension study. Results from that study showed that women continued to benefit from treatment with leuprolide acetate for nearly one more year.

"Our trial result demonstrates that leuprolide acetate may benefit a spectrum of women with mild-to-moderate Alzheimer's disease for a sustained period of time," said Dr. Joseph DeVeaugh-Geiss, Voyager's interim chief medical officer. "These findings are encouraging as we continue to make progress with our trials in Alzheimer's disease."

Voyager is currently enrolling subjects for two Phase III clinical trials investigating the safety and efficacy of VP4896 (leuprolide acetate implant) in the treatment of mild-to-moderate Alzheimer's disease. Enrollment for the first trial is well ahead of schedule. Voyager expects to complete enrollment of all 555 subjects before Dec. 31, 2006.

At ICAD 2006, members of Voyager's team will also be presenting four scientific/clinical posters relating to the Phase I and II clinical trials, preclinical research linking leuprolide acetate to AD pathology and a "Hot Topics" poster that addresses data from both of Voyager's Phase II studies.

About the Phase II Study

The data presented are the results of a subgroup analysis of Voyager's 48-week double blind, placebo-controlled Phase II study. The study assessed the efficacy and safety of leuprolide acetate in stabilizing cognitive and global function in women age 65 and older with mild-to-moderate Alzheimer's disease.

The primary efficacy endpoints of the trial were scores on both the ADAS- Cog (a test of memory and cognition) and the ADCS-CGIC (a global measure of a subject's change in condition) at 48 weeks compared to baseline. There were various secondary efficacy endpoints, including scores on the ADCS-ADL (a measurement of a patient's capacity to perform activities of daily living) at 48 weeks compared to baseline.

In the subgroup analysis, the mean ADAS-Cog score in the group receiving the high dose of leuprolide acetate and an AChEI declined by 0.18 points from baseline at week 48 compared to a mean decline of 3.30 points in the group receiving placebo and an AChEI.

In the ADCS-CGIC analysis, 58 percent of the subgroup receiving the high dose of leuprolide acetate and an AChEI scored no change or better at week 48 in comparison with baseline versus 38 percent of the subgroup receiving placebo and an AChEI.

The mean ADCS-ADL score in the subgroup receiving the high dose of leuprolide acetate and an AChEI declined 0.54 points from baseline at week 48 compared to a mean decline of 6.85 points in the subgroup receiving placebo and an AChEI.

About Voyager Pharmaceutical Corporation

Voyager Pharmaceutical Corporation is a biopharmaceutical company focused on developing drugs for diseases associated with aging and development. Voyager's scientific approach is based on the observation that many diseases of aging may be caused by changes in human reproductive hormone levels that are characteristic of the aging process.

Voyager's most advanced product candidate is VP4896, a proprietary, small, biodegradable implant that is comprised of leuprolide acetate and a polymer. VP4896 decreases the amount of luteinizing hormone (LH) released by the pituitary gland. Based on clinical evidence, Voyager believes that the reduction of LH may decrease or slow the progression of Alzheimer's disease.

The active ingredient in VP4896, leuprolide acetate, has been used safely for over 20 years as a treatment for prostate cancer. Voyager's phase III trial program for VP4896 is investigating the effects of this new AD therapy on the rate of cognitive decline in mild-to-moderate Alzheimer's disease.

http://www.medicalnewstoday.com/medical ... wsid=47484

[Paolo]

"The Week" recently reported that THC -yep, smoking pot - can help with Alzheimer's too. Let's get Grandma stoned...