New Drug Shows Early Promise in Treating Parkinson's Psychosis

Pimavanserin may have fewer side effects than current therapy, study suggests

 

Many people living with Parkinson's disease suffer from hallucinations and delusions, but an experimental drug might offer some relief without debilitating side effects.

The drug -- pimavanserin -- appears to significantly relieve these troubling symptoms, according to the results of a phase 3 trial to test its effectiveness.

Such symptoms affect as many as half of the estimated 7 million to 10 million Parkinson's patients around the world, according to study background information.

Currently, patients are treated with antipsychotic drugs such as clozapine and quetiapine, which worsen Parkinson's motor symptoms, hasten mental decline, increase the risk of stroke and can be life-threatening, authors of the new study said.

Their study was published in the Nov. 1 online issue of The Lancet and funded by Acadia Pharmaceuticals, the makers of pimavanserin.

"There are no first-line approved treatments for psychosis in people with Parkinson's disease," said lead researcher Dr. Clive Ballard, a professor of age-related diseases at King's College, London.

"Existing antipsychotics are either ineffective or not tolerated. Pimavanserin is not yet licensed, but could potentially offer a change in the treatment of these distressing and impactful symptoms," he said.

An expert not involved with the study talked about the need for a medication alternative.

"The Parkinson's disease community has been waiting for a potentially new approach for the treatment of psychosis and hallucinations," said Dr. Michael Okun, national medical director of the National Parkinson Foundation.

"Pimavanserin may offer a relatively safe and reasonably efficacious choice for many patients in the situation where the current therapies are not adequate," Okun added.

The new drug works differently from other antipsychotics, study author Ballard said.

Pimavanserin blocks certain receptors -- called serotonin 5-HT2A receptors -- in the neocortex of the brain. This part of the brain is responsible for sensory perceptions, conscious thought and language, and is associated with hallucinations and delusions, Ballard explained.

For the trial, Ballard's team randomly assigned 199 Parkinson's patients suffering from disease-associated psychosis to daily doses either of pimavanserin or an inactive placebo pill.

After 43 days, patients taking pimavanserin showed a significant improvement on a scale of psychotic symptoms compared to those given a placebo -- 37 percent versus 14 percent.

However, this early study only provided short-term results, another expert pointed out.

Frances Weaver, director of the Center for Management of Complex Chronic Care at Hines VA Hospital, in Illinois, said although the trial was promising, more needs to be known about the long-term picture for this drug.

"The follow-up was only 43 days," she said. "It will be important to examine the long-term effects of this medication as psychosis is an ongoing problem which will likely require the patient to remain on medications for the rest of his life. Questions about long-term tolerability and effectiveness still need to be answered."

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Blood Test for Pancreatic Cancer Shows Promise in Early Trial

But the screen is meant only for people already at high risk for the deadly illness, experts say

 

Pancreatic cancer is one of the most lethal tumor types because it's too often diagnosed in a later, advanced stage. But a new study suggests that a simple blood test might help spot the disease earlier.

The study is described as small and preliminary, and investigators cautioned that the initial findings will need to be confirmed in larger trials.

"Pancreas cancer is the fourth leading cause of cancer death in the United States," said study coauthor Dr. Nita Ahuja, an associate professor of surgery in the department of oncology and urology at the Johns Hopkins University School of Medicine, in Baltimore. "There have been minimal to no improvements in the survival from this disease in the last 40 years. There are over 40,000 people diagnosed every year and about that many deaths."

"One of the main reasons for the lethal nature of this cancer is that most cancers are diagnosed too late once they have spread to other organs," Ahuja said. "Around 8 percent have spread to distant organs such as the liver or lungs, while another 10 percent have locally spread to major blood vessels. However, in the patients where cancer can be detected early and has not spread, a long-term cure is possible with surgical removal of the cancer with the surrounding lymph."

Any means of spotting the cancer early would therefore be crucial, Ahuja added. "We have mammograms to screen for breast cancer and colonoscopies for colon cancer, but we have had nothing to help us screen for pancreatic cancer," she said.

Ahuja said the new study sought to find blood "markers" for pancreatic cancer "in patients who are at increased risk for developing this cancer, such as [those with a] family history or heavy smokers."

Ahuja's team had previously identified mutations in two genes, called BNC1 and ADAMST1, that typically occurred in the presence of pancreatic cancer. Since both mutations are found in 97 percent of early stage pancreatic cancer tissues, the researchers developed tests to search for signs of the mutations in blood samples collected from 42 people already diagnosed with early stage pancreatic cancer.

Reporting in the current online edition of the journal Clinical Cancer Research, Ahuja's team said both genetic markers were found in 81 percent of the tested blood samples, but not in samples taken from patients who either did not have pancreatic cancer or had a history of pancreatitis (an inflamed pancreas).

The researchers said the results are much more impressive than, for example, the prostate-specific antigen (PSA) test used to screen for prostate cancer, which has roughly a 20 percent success rate.

Still, an 81 percent accuracy rate is "far from perfect," Ahuja said. The test also had a false-positive rate of 15 percent, meaning that 15 percent of people who get the test initially will be told they might have pancreatic cancer when that is not the case.

And Ahuja stressed that the test is not designed as a screen for the population as a whole -- only for those already deemed to be at high risk for the disease.

"The eventual goal is to develop a cost-effective test to test patients who are at high risk," she said. "The beauty of this test is that it can be repeated every year as you go for your annual physical."

Dr. Smitha Krishnamurthi is an associate professor of medicine in the division of hematology and oncology with University Hospitals Case Medical Center & Case Western Reserve University School of Medicine, in Cleveland. She applauded the research, saying that "if pancreatic cancer could be detected at an early stage, more patients would be cured."

"This study presents an encouraging step in the right direction," Krishnamurthi said. "The authors have developed a blood test that detected the earliest stage of pancreatic cancer and correctly identified most of the healthy individuals tested. However, this was a very small study. The blood test must be studied in many more patients with early stage pancreatic cancer and healthy individuals to really know if it will be an accurate and reliable screening test for pancreatic cancer."

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Study of Twins Shows How Smoking Ages the Face

Siblings who smoked had more wrinkles, creases, droops and jowls

A study comparing the faces of identical twins confirms what many smokers fear -- the habit does prematurely age a person's skin, taking a serious toll on looks even after just five years.

Researchers from Case Western Reserve University in Ohio used the annual Twins Day Festival in Twinsburg, Ohio, to identify 79 pairs of twins in which one sibling smoked and the other didn't.

The twins who were smokers showed many more signs of skin aging, the researchers found. Their faces featured more wrinkles, creases, droops and jowls.

"Smoking harms virtually every organ in the body, including your skin," said Danny McGoldrick, vice president for research at the Campaign for Tobacco-Free Kids. "Whether you are doing it for vanity or your health, one of the most important health decisions of your life is not to start smoking, or to quit if you have."

The research team attended the Twins Day Festival every year between 2007 and 2010, eventually finding 79 pairs of twins to compare. The twins filled out questionnaires regarding their smoking and lifestyle, and professional photographers snapped individual pictures of them both.

A panel of three plastic surgeons then analyzed the twin's facial features, grading the amount of aging they saw in each person's face using a standardized assessment tool. The researchers used questionnaire results to control for other factors that might prematurely age skin, including sun damage, alcohol use and work stress.

Twins who smoke, when compared to their nonsmoking siblings, had worse scores for baggy eyes, baggy cheeks, smile lines and wrinkles along their upper and lower lips.

Researchers also compared the faces of twins who both smoke, but one of the pair had been smoking for at least five years longer than his or her sibling. They found more baggy eyes, baggy cheeks and lower-lip wrinkles in twins who had been smoking longer.

The judges identified the smoking twin as appearing older in photographs 57 percent of the time compared with the nonsmoking twin, and the twin who had smoked for a longer period of time was identified as older about 64 percent of the time.

The premature aging caused by smoking seemed to mainly affect the lower two-thirds of a person's face, the authors said. There were no apparent differences between smokers and nonsmokers when it came to forehead wrinkles or crow's feet, for example.

The study was published in the November issue of the journal Plastic and Reconstructive Surgery.

Smoking can affect a person's skin tone by robbing cells of needed oxygen, said Dr. Cheryl Healton, president and CEO of the anti-tobacco advocacy group Legacy.

"It's widely known that tobacco causes cardiac problems and disrupts oxygenation," Healton said. "Getting good oxygenation really affects a person's complexion."

Smoking also might cause wrinkles, folds and droops by damaging connective fibers like collagen and elastin that help maintain skin elasticity, the researchers added.

"A less taut skin envelope cannot counteract the effects of gravity," they said.

Healton said people should heed the findings as yet another reason to quit smoking immediately. As the study found, even five years can make a difference, she said.

"It's really bad to smoke, and it definitely affects your appearance," she said. "Not smoking is good for your looks."

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