Snuffing Out Alzheimer’s

confusedHot on the heels of Friday’s blog – Sniffing Out Alzheimer’s, British scientists just announced a major breakthrough that could, one day, result in a treatment for Alzheimer’s, Parkinson’s, Huntington’s and other neurodegenerative diseases.

In tests on mice, researchers from the toxicology unit of the Medical Research Council showed brain cell death from prion disease could be prevented.

Professor Roger Morris, from King’s College London, said: “This finding, I suspect, will be judged by history as a turning point in the search for medicines to control and prevent Alzheimer’s disease.”

It is rare to get cautious scientists keen to describe any study as a turning point in history, let alone a study in mice.

miceNot only is it is early science, a lot can go wrong between a drug for mice and a drug for humans and the only published data is for prion disease, not even Alzheimer’s.

So why the excitement?

It is the first time that any form of neurodegeneration has been completely halted, so it is a significant landmark. It shows that the process being targeted has serious potential.

The research team focused on the natural defense mechanisms built into brain cells. When a virus hijacks a brain cell it leads to a build-up of viral proteins. Cells respond by shutting down nearly all protein production in order to halt the virus’s spread.

neurodegenerative diseaseHowever, many neurodegenerative diseases involve the production of faulty or “misfolded” proteins. These activate the same defenses, but with more severe consequences. The misfolded proteins linger and the brain cells shut down protein production for so long that they eventually starve themselves to death.

This process, repeated in neurons throughout the brain, can destroy movement or memory or even kill, depending on the disease.  It  is thought to take place in many forms of neurodegeneration, so safely disrupting it could treat a wide range of diseases.

The researchers used a compound which prevented those defense mechanisms kicking in and in turn halted neurodegeneration.

The study showed mice with prion disease developed severe memory and movement problems. They died within 12 weeks. However, those given the compound showed no sign of brain tissue wasting away.

Lead researcher Professor Giovanna Mallucci says: “They were absolutely fine, it was extraordinary. What’s really exciting is a compound has completely prevented neurodegeneration and that’s a first. This isn’t the compound you would use in people, but it means we can do it and it’s a start.

She said the compound offered a “new pathway that may well give protective drugs” and the next step was for drug companies to develop a medicine for use in humans.

Side effects are an issue. The compound also acted on the pancreas, meaning the mice developed a mild form of diabetes and lost weight. Any human drug would need to act only on the brain.

David Allsop, professor of neuroscience at Lancaster University described the results as “very dramatic and highly encouraging.”

SRxA’s Word on Health agrees.  We look forward to seeing further research and how these findings could apply to diseases such as Alzheimer’s and Parkinson’s.

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Pumped Up about Promising new Parkinson’s Pump

parkinson-disease60Parkinson’s disease, as many of our readers know is a chronic, progressive neurological disease that causes sufferers to lose control of body movements, resulting in tremors, muscle stiffness, loss of balance and a host of other problems. Currently, there is no cure for Parkinson’s disease and treatment options are limited. Therapy is directed at treating the symptoms that are most bothersome and for this reason, there is no standard or “best” treatment for that applies to every patient.

Treatment approaches include medications and surgery (deep brain stimulation) as well as general lifestyle modifications (rest and exercise), physical, occupational and speech therapy.

levodopaAmong the drug-related therapies, levodopa is considered one of the most effective for relieving the symptoms of Parkinson’s disease. It helps reduce tremor, stiffness, and slowness and helps improve muscle control, balance, and walking. Levodopa does not slow the disease process, but it improves muscle movement and delays severe disability. So far, levodopa, which had been used to treat Parkinson’s since the 1970’s, has only been available in pill form.

But a new Cleveland Clinic study finds that using a pump to administer a gel form of levodopa directly into the small intestine is much more effective.

Neurologist Hubert Fernandez, MD, who led the study, says, “The levodopa pump decreased or improved what we call the ‘bad time’ in Parkinson’s patients by up to four hours per day.” The levodopa can control this ‘bad time’ — the tremors, muscle spasms and other movement disorders that makes it difficult for Parkinson’s patients to function on a daily basis.

parkinsons-gel-drug-pump-190x155This is an amazing finding,” says Fernandez. “We know of no other oral therapy that will improve the bad time in Parkinson’s by an average of four hours daily.”

The levodopa pump is external. It sits in a pouch under the patient’s shirt and provides a steady dose of the drug. The levodopa gel is administered directly into the small intestine, where most of the drug is absorbed. The constant dose makes the body’s movements more controlled and predictable, making it easier for people with the disease to plan and go about their day without worrying that the drug’s effects will wear off.

The biggest advantage of the levodopa is its efficacy,” Dr. Fernandez says. “We’re trying to deliver it on a continuous basis so the patients don’t need to take it every hour.” parkinsons gel pump

69-year-old Bob Van Housen has been living with Parkinson’s disease for over 12 years.  Prior to enrollment in the study he was having to take up to five levodopa pills every three hours to control his symptoms. Even then, his symptoms progressed to the point where it was hard to keep up.  “He was ‘off’ for at least seven hours,” said Van Housen’s wife, Carol. “Seven hours is a long time to not be able to function every day.”

The couple often had to cut their trips together short and limit their social outings outside of the house. Van Housen says that being part of the trial at Cleveland Clinic has been life-changing. “We can predict better how I’m going to feel and how I’m going to act and can plan trips and work around those times when I otherwise would have been problematic.”

The gel pump which is not yet available in the United States is currently under review by the Food and Drug Administration. Let’s hope it doesn’t hit any hurdles along the way, so others with Parkinson’s can avoid the roller-coaster of symptoms and enjoy the type of benefits that Bob has experienced.

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Parkinson’s Disease Therapy May Cause More Harm Than Good

parkinsons 1In a surprise finding, a study by researchers from NorthShore University HealthSystem and the Mayo Clinic provides genetic and clinical evidence that some new Parkinson’s disease therapies may actually accelerate disease progression and increase the risk of becoming physically incapacitated and demented.

Specifically problematic are those therapies that target the expression of alpha-synuclein – a protein whose function in the healthy brain is unknown, but is a major constituent of Lewy bodies, protein clumps that are the pathological hallmark of Parkinson’s disease.

AlphaSynuclein3Since its discovery as a cause of familial Parkinson’s disease nearly 20 years ago, alpha-synuclein has been the focus of intensive efforts by researchers working to definitively characterize the protein’s role in idiopathic Parkinson’s disease and its potential as a target for neuroprotective therapies.

This news is particularly concerning given that a vaccine targeting alpha-synuclein in Parkinson’s patients is currently undergoing clinical testing in Parkinson’s patients and a number of molecules that target the protein for reduction are in advanced stages of preclinical development.  The vaccine candidate, from Austrian biotech AFFiRiS, works by binding to alpha-synuclein and subsequently clearing it from the brain.

parkinsons-diseaseAs of January 2012, The Michael J. Fox Foundation had invested over $47 million in projects targeting alpha-synuclein.

Our research suggests that therapies that seek to suppress alpha-synuclein in Parkinson’s disease may actually accelerate the disease process and increase the risk for developing severe physical disability and dementia,” said lead author Demetrius M. Maraganore, MD. “We believe it is our responsibility to release these data because this type of treatment may have long-term harmful effects.”

For the first time, we observed that, while over-expression of alpha-synuclein increases the risk for developing Parkinson’s disease, conversely, under-expression is associated with worse motor and cognitive outcomes after the disease starts,” adds study author Katerina Markopoulou, MD, PhD, a neurologist at NorthShore.

The researchers followed 1,098 Mayo Clinic patients for nearly 15 years  and sequenced the patients’ DNA to determine the presence of gene variants that regulate how much alpha-synuclein protein is made. They also studied the association of these gene variants with patients’ survival free of severe motor and cognitive disabilities.

Patients who had reduced expression of alpha-synuclein had a 23% greater risk of becoming wheelchair-dependent or developing dementia.

If replicated, the findings, presented Wednesday at the annual meeting of the American Academy of Neurology will have profound implications regarding therapies under development for Parkinson’s disease.

hands_ParkinsonsInterestingly, this is not the first time alpha-synuclein has been challenged. SRxA’s Word on Health has discovered literature from 2008 showing that there are people with Parkinson’s Disease that have no accumulation of alpha-synuclein, and people who have accumulated alph-synuclein who do not have Parkinson’s Disease. In autopsy studies, 30%-55% of elderly subjects with widespread alpha-synuclein pathology were found to have no definite neuropsychiatric symptoms; yet when large amounts of alpha-synuclein had fewer patients were found to have Parkinson’s Disease.  These authors concluded that much of the Parkinson’s Disease research was being done without having any scientific or factual basis.

Looks like  people should have listened!

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Papal Poor Health

frail Pope On February 11, Pope Benedict XVI stunned the Catholic Church and the world when he announced his resignation by saying he no longer had the mental and physical strength to carry on.

At 8pm local time yesterday, he ended his difficult reign, marking the first time in six centuries a pope has resigned instead of ruling for life.

But what do we really know of his health or that of other popes before him?

The Vatican recently confirmed Benedict had a pacemaker for years, indicating a long-standing heart problem. And his older brother told the press that age had taken its toll.

Other observers have noticed the pope’s reduced energy. The press reported that he was ferried to the altar at St. Peter’s for Midnight Mass Christmas Eve on a wheeled platform and then appeared to doze off during the service.

Pope frailVisiting Mexico last year, he awoke at night and couldn’t locate a light switch in his room, then fell and bloodied his head when he hit the bathroom sink.

Beyond these few facts, we know very little about the health problems that led Benedict to announce his retirement. We don’t even really know if his flagging stamina was the true reason behind his resignation.

And while Pope Benedict XVI might be the first Holy Father to voluntarily resign because of old age and deteriorating health, the papacy has a past medical history of poor health.  According to the history books, these ailments range from depression to gout to cancer.

According to church law, as long as a pope is able to conduct Mass, he can continue in his role even if he is suffering, in pain or even bedridden, as was the case with Pope Alexander VII.

Pope Alexander VII’s surgeon and confessor tried to persuade him not to go before the crowd on Easter Sunday of 1667, but he did it anyway. The pope died three days later, according to author Wendy J. Reardon in The Deaths of the Popes.”

Pope_Clement_XII,_portraitMore than a century later, Pope Clement XIV became known as the pope who drooled and had eyes that “darted in their bulging sockets” as he fearfully clung to walls for fear of a Jesuit assassination attempt. He died after correctly predicting his own death in 1774.

In 1958, Pope Pius XII died after enduring recurring bouts of hiccoughs for five years. At one point, his hiccoughs became so intense, that they tore the lining of his stomach. He died of complications from pneumonia at 82 years old.

Pope John Paul II, was sick until he died on April 2, 2005 at 85 years old. He lived with Parkinson ‘s disease for decades, but he died of cardio-respiratory failure, kidney failure and septic shock.

Death has never been an issue that has worried popes,” says papal historian Anura Guruge,  “Popes talk about no purgatory for popes.” Instead they believe if God is ready for a new pope, he will simply call the current one home to heaven where they will immediately be admitted to God’s house and be in the presence of the Holy Father. Not surprising then, that many popes have gone so far as to express enormous amounts of joy on their death beds.

Emeritus Pope Benedict XVI, was one of the oldest popes when he was elected in 2005 at age 78. In 1991 he had a stroke that reportedly temporarily affected his vision. He fell in 1992 and again 2009. He was also thought to have either arthritis or arthrosis, a similarly painful and debilitating joint condition.

Father Virgilio Elizondo, a professor at the University of Notre Dame in Indiana, said he thinks Pope Benedict XVI made a very difficult but wise decision by resigning. He added that the papacy has a history of unpredictability, and the surprise resignation fits right in.

pope John paulI think when you consider the sincerity of the man, when you consider the weight of the universal church, and the greatest variety of issues affecting the church and the rest of the world, I could see how he could come to that decision,” says Elizondo. “What’s really needed is a younger person with more vigor and up-to-date knowledge about what’s happening. I think that’s the rationality behind this pope.

But not everyone agrees.  “This pope’s resigning is essentially overriding God’s will,” said Guruge. “We had suspected that he had more health issues than had been made public. … A pope resigning is really not the right thing to do.”

Pope Benedict XVI was just 73 days away from being the third oldest pope. However, he will remain the fourth oldest pope because his resigned before his 86th birthday. The three older popes were Pope Clement X, who lived to be just over 86 years old; Pope Clement XII, who lived to be 87; and Pope Leo XIII, who before his death at 93 was known as the “eternal pope” because he kept on living! Back then, it might be argued, the job was less demanding because the pope didn’t have to be on television or travel the world or tweet.

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Out Pacing Alzheimer’s

Woman and elderly mother talking to a doctorAlzheimer’s disease is the most common form of degenerative dementia, afflicting about 5.5 million Americans and costing more than $100 billion per year. In terms of U.S. health care expenditure it now ranks as the third costliest disease.

Alzheimer’s disease is not easily managed. It becomes progressively disabling with loss of memory, cognition, worsening behavioral function and a gradual loss of independent functioning. Currently there is no cure.

Kathy SandfordBut this may be all about to change. Last October, during a five-hour surgery at The Ohio State University Wexner Medical Center, Kathy Sanford became the first Alzheimer’s patient in the United States to have a pacemaker implanted in her brain.

Could this be the dramatic shift in the disappointing struggle to find something to slow the damage of this epidemic?  As yet, no one knows if it might work, and if it does, how long the effects might last.  Research is still in its infancy.

Dr. Douglas Scharre, neurologist and director of the division of cognitive neurology, and Dr. Ali Rezai, neurosurgeon and director of the neuroscience program are jointly conducting the study.

Sanford is the first of up to 10 patients who will be enrolled in the FDA-approved study to determine if using a brain pacemaker can improve cognitive and behavioral functioning in people with Alzheimer’s disease.

brain pacemakerThe study employs the use of deep brain stimulation (DBS), the same technology used to successfully treat patients with movement disorders such as Parkinson’s disease.

First, holes are drilled into the patient’s skull so tiny pacemaker wires can be implanted into just the right spot. A battery-powered generator near her collarbone then sends tiny shocks up her neck and into her brain.

It is hoped that zapping the brain with mild jolts of electricity will make the brain work better and stave off the cognitive, behavioral and functional effects of Alzheimer’s disease.

If the early findings that we’re seeing continue to be robust and progressive, then I think that will be very promising and encouraging for us,” says Ali Rezai MD, “But so far we are cautiously optimistic.”

Kathy Sanford says she volunteered for the study to help others avoid the angst she has suffered as Alzheimer’s slowly disrupted her life.  The Ohio woman’s early stage Alzheimer’s was gradually getting worse. She still lived independently, posting reminders to herself, but no longer could work. The usual medicines weren’t helping.
Her father is proud that his daughter is participating in the study. “What’s our choice? To participate in a program or sit here and watch her slowly deteriorate?” asked Joe Jester, 78.  He drives his daughter to follow-up testing, hoping to spot improvement.

cognitive testingSince having the surgery last October Sanford has undertaken a number of problem-solving tests while neurologists adjusted the voltage and frequency and watched her reactions.

She was cheered to see her test scores climb a bit during those adjustments. While she knows there are no guarantees, she says “if we can beat some of this stuff, or at least get a leading edge on it, I’m in for the whole deal.”

Her optimism and hope is shared by her neurologist. “We’re getting tired of not having other things work” said Douglas Scharre MD.  Alzheimer’s doesn’t just steal memories. It eventually robs sufferers of the ability to do the simplest of tasks.

Here’s hoping these brain pacemakers can reconnect some of the circuits and diminish such losses.

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Keeping harmful protein fibers at bay

Misfolded clothes, are the bane of many a fashion retail worker’s existence; misfolded proteins on the other hand are not just useless,  they can also be toxic. When proteins in the human body get out of alignment they form linear aggregates known as amyloid fibers that can lead to disorders such as Alzheimer’s and Parkinson’s diseases.

So SRxA’s Word on Health was interested to learn that US researchers have discovered a protein machinery that inhibits the formation and helps to dissolve such fibers.

The researchers set out to study whether two small heat shock proteins (HSPs) – proteins that assist other proteins in folding – could affect the generation of amyloid fibres by a misfolded protein of the same organism (Sup35). Using purified proteins, derived from baker’s yeast they showed that Hsp26 and Hsp42 inhibited amyloid formation.

Even cleverer still, they were able to determine exactly which steps of the process were affected. Hsp42 slowed down early structural reorganization of small aggregates before the fibers were formed, whereas Hsp26 inhibited fiber growth.

All of which, we’re sure you’re saying, is great news for baker’s yeast, but you’ve never seen a loaf of bread with Alzheimer’s!

And here’s the problem.   Humans and other animals lack the yeast enzyme – Hsp104 – that rapidly dissolves amyloid.  As such, it was unclear if and how our cells could get rid of amyloid fibres.

Undeterred, the scientists started to experiment further.  They showed that Sup35 fibers can be dissolved by a combination of several yeast HSPs (Hsp40, Hsp70 and Hsp110) in the absence of Hsp104.  And, the effect was even better if the fibers were pretreated with Hsp26 and Hsp42.

What’s more, they obtained similar results when using the equivalent human HSPs to disaggregate the amyloid fibres involved in Parkinson’s disease. Although amyloid disassembly took many days, the researchers propose that such system could work in long-lasting cells such as neurons.

The full results are published here.

While their findings suggest that enhancing the activity of certain HSPs in affected cells and/or introducing yeast Hsp104 could help to dissolve the amyloid in disorders such as Parkinson’s disease, additional research would be needed to assess the efficacy and safety of such treatments before human testing can begin.

Nevertheless it’s a step in the right direction.  Now, if only we could find an answer to misfolded clothes!

Getting Cheery Over Cherries!

Regular readers of SRxA’s Word on Health will be familiar with the many claimed health benefits of fruit. Bananas for HIV prevention, citrus to safeguard us against stroke, berries to prevent Parkinson’s Disease and even exotic cupuaçu for improved reproductive health.

According to many, including TV’s Dr. Oz, the latest superfruit on the block is tart cherries. Extensive research has linked the delicious bright red fruit to a number of benefits, including better sleep, reduced pain from gout and arthritis, reduced post-exercise muscle and joint pain as well as reduced cholesterol, and decreased risk for atherosclerosis and metabolic syndrome.

Dr. Oz, has gone so far as to say that tart cherries are the ultimate antioxidant.

New research from Oregon Health & Science University presented last week at the American College of Sports Medicine Conference confirmed that tart cherries can help to reduce chronic inflammation and can help people with osteoarthritis manage their disease.

In a study of twenty women ages 40 – 70 with inflammatory osteoarthritis, the researchers found that drinking tart cherry juice twice daily for three weeks led to significant reductions in important inflammation markers – especially for those women who had the highest inflammation levels at the start of the study.

With millions of Americans looking for ways to naturally manage pain, it’s promising that tart cherries can help, without the possible side effects often associated with arthritis medications,” said principal study investigator Kerry Kuehl, M.D. “I’m intrigued by the potential for a real food to offer such a powerful anti-inflammatory benefit – especially for active adults.”

Often characterized as “wear and tear” arthritis, osteoarthritis is the most common type of arthritis. Athletes are often at a greater risk for developing the condition, given their excessive joint use that can cause a breakdown in cartilage and lead to pain and injury.

Anthocyanins – the antioxidant compounds in tart cherries – appear to reduce inflammation to levels comparable to some well-known pain medications.

Previous research on tart cherries and osteoarthritis found that a daily dose of tart cherries helped reduce osteoarthritis pain by more than 20%.

Leslie Bonci, Director of Sports Nutrition at the University of Pennsylvania Medical Center for Sports Medicine, has incorporated tart cherries into the training menu of her professional athletes. She claims they are a natural and easy way to manage pain and also taste great.

Never heard of tart cherries, or concerned that they have such a short season?  The great news is that they are available year-round in dried, frozen, powder and juice forms too.

The Doctor Will See You All Now!

Overcrowded waiting room and endless wait times may soon  be a thing of the past. At least for patients with Parkinson’s disease.

According to a  study published in the online issue of Neurology, group appointments may be feasible for patients with Parkinson’s disease. Group visits  allow patients more time with their doctor, provide more opportunity for disease management education and allow patients and their caregivers to share their experiences and learn from one another

The study compared patients who received normal care from their physician with patients who had underwent group visits. The “normal care” group had 30-minute appointments with their physicians every three to six months. Group visits lasted 90 minutes and were held every three months and included introductions, updates from patients, and an educational session on a topic chosen by the participants. Time was allotted for questions from patients or caregivers, and individual 10-minute appointments with the physician were scheduled for before or after the group visit for individual concerns.

Of the 30 study participants, 90% completed the 12 month study, along with 93% of the 27 participating caregivers. At the end of the study, there was no difference between those receiving normal care and those participating in the group visits in how they rated their overall quality of life.

Participants were also asked whether they preferred the group visits or usual care. Of those receiving group visits two thirds said they preferred them. Among the normal care group, opinions were roughly divided.

While both support groups and traditional visits have clear benefits, a survey of people with Parkinson’s showed that they desire more information for them and their caregivers about their disease,” said study author E. Ray Dorsey, MD, MBA, of Johns Hopkins University School of Medicine.

Group visits can give physicians the opportunity to observe their patients for a longer period of time and appreciate disease characteristics such as fluctuations in their symptoms and daytime sleepiness that may not readily be appreciated during a routine 20- to 30-minute office visit.  However, they may also pose logistical issues, such as scheduling difficulties and the need for a large room. Additionally, there is a potential risk that the lack of a one-on-one examination could lead physicians to miss subtle problems and also some concerns about patient confidentiality.

Perhaps what is needed is a hybrid model – where patients alternate between group and individual appointments.

Have you experienced a group appointment?  Would you be willing to have a group appointment? Please share your thoughts with us.

Sweet Protection Against Parkinson’s Disease

New research shows men and women who regularly eat berries may have a lower risk of developing Parkinson’s disease.  Men may further lower their risk by regularly eating apples, oranges and other sources rich in dietary flavonoids.

The study which was supported by the National Institutes of Health involved 49,281 men and 80,336 women. Researchers gave participants questionnaires and used a database to calculate intake amount of flavonoids. They then analyzed the association between flavonoid intakes and risk of developing Parkinson’s disease. They also analyzed consumption of five major sources of foods rich in flavonoids: tea, berries, apples, red wine and oranges or orange juice. The participants were followed for 20 to 22 years.

During that time, 805 people developed Parkinson’s disease. In men, the top 20% who consumed the most flavonoids were about 40% less likely to develop Parkinson’s disease than the bottom 20% of male participants who consumed the least amount of flavonoids.

In women, there was no relationship between overall flavonoid consumption and developing Parkinson’s disease. However, when sub-classes of flavonoids were examined, regular consumption of anthocyanins, which are mainly obtained from berries, were found to be associated with a lower risk of Parkinson’s disease in both men and women.

This is the first study in humans to examine the association between flavonoids and risk of developing Parkinson’s disease,” said study author Xiang Gao, MD, PhD, with the Harvard School of Public Health in Boston.

Fruit consumption has also been related to health benefits in a whole range of conditions including cancer, stroke, heart disease, diverticulosis, hypertension, cataracts, diabetes, asthma, and bronchitis.

Do you have any fruity stories to share?  SRxA’s Word on Health would love to hear from you.