INVESTIGATIONAL THERAPY FOCUSES ON SLOWING PROGRESSION IN MILD TO MODERATE ALZHEIMER’S
Houston Methodist’s Nantz National Alzheimer Center only Texas site to offer this study
From FMS Global News Desk of Jeanne Hambleton Released: 20-Aug-2014
Source Newsroom: Houston Methodist
Newswise — Patients with mild to moderate Alzheimer’s disease currently have no treatment options to slow brain cell deterioration. Researchers at Houston Methodist’s Nantz National Alzheimer Center are studying an investigational drug that proposes to do just that.
T-817MA focuses on preventing brain cell loss and slowing disease progression, whereas current treatment options including Donepezil (Aricept®), Rivastigmine (Exelon®), and Memantine (Namenda™) merely treat the symptoms of mild to moderate Alzheimer’s. The researchers want to know whether the investigational therapy using T-817MA can prevent brain cell loss, slowing disease progression in a more fundamental way.
Houston Methodist is the only study location in Texas to offer this randomized, double-blind, placebo-controlled study. Approximately two-thirds of study participants will receive active study drug, but neither the patient nor the study personnel will know whether patients received the active study drug or placebo until the patients’ participation in the study is complete. This is a Phase II clinical trial, an early study assessing the efficacy of a drug that has been tested on relatively few research subjects.
“Previous studies in mice have shown this investigational drug may work by protecting brain cells, which would result in improved memory and cognition,” said Joseph C. Masdeu, M.D., Ph.D., principal investigator of this study at Houston Methodist and director of the NNAC.
“As someone who sees the devastating impact this disease has on patients and their families, our goal is to find out if this drug is a viable option for our patients.”
Of the more than five million Americans living with Alzheimer’s disease, almost two-thirds are women. American women are twice as likely to die of Alzheimer’s disease as they are from breast cancer. According to the Alzheimer’s Association, someone develops Alzheimer’s every 67 seconds. In 2013, 15.5 million caregivers provided an estimated 17.7 billion hours of unpaid care valued at more than $220 billion.
People already diagnosed with mild to moderate Alzheimer’s may be eligible for this study if they are women or men aged 55-85; they have taken donepezil (Aricept) treatment for at least six months; live in the community, not in a nursing home or assisted-living facility; and have a study partner who has regular contact with the patient (at least 10 hours per week) and can attend study visits.
This study is sponsored by Toyama Chemical Co., Ltd., and is being conducted by the Alzheimer’s Disease Cooperative Study (ADCS), the largest Alzheimer’s disease therapeutic research consortium in the United States and supported by the National Institute on Aging. Approximately 50 clinical sites nationwide will offer the study to 450 patients with mild to moderate Alzheimer’s disease. Houston Methodist expects to enroll approximately 20 patients. For study questions, call 281.222.9983.
Emmy Award-winning sports commentator, Jim Nantz, partnered with the Houston Methodist Neurological Institute to create the Nantz National Alzheimer Center. Jim and his wife, Courtney, work tirelessly to increase funding for research and generate awareness of dementia and Alzheimer’s disease, as well as the possible effects that concussions and traumatic brain injuries have on these diseases. Courtney and Jim have made a generous lifetime commitment to aggressively support research to find a cure for Alzheimer disease as a lasting tribute to Jim’s father, Jim Nantz, Jr. who battled Alzheimer’s for 13 years
SOME ANTI-INFLAMMATORY DRUGS AFFECT MORE THAN THEIR TARGETS
Discovery of changes to cell membranes has wide repercussions for drug developers
From the FMS Global News Desk of Jeanne Hambleton Citations Cell Reports, Aug-2014; Embargoed: 21-Aug-2014 Source: Johns Hopkins Medicine
Newswise — Researchers have discovered that three commonly used nonsteroidal anti-inflammatory drugs, or NSAIDs, alter the activity of enzymes within cell membranes. Their finding suggests that, if taken at higher-than-approved doses and/or for long periods of time, these prescription-level NSAIDs and other drugs that affect the membrane may produce wide-ranging and unwanted side effects.
More positively, the researchers say, their work provides the basis for a test that drug developers can use to predict and perhaps avoid these side effects in new medicines they make. A summary of the results will be published online in the journal Cell Reports on Aug. 21.
“When drug designers think about possible sources of side effects, they tend to think about which proteins are similar to the protein they are targeting, and they make sure that the former are not affected by the drug,” says Sinisa Urban, Ph.D., an associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator. “But our group has found that drugs that affect the cell membrane can alter the activity of proteins that are totally unrelated to the target.”
Working with Syed Moin, then a postdoctoral fellow in his laboratory, Urban’s project began as an investigation into the role of the cell membrane in the activity of a group of “cellular scissors” embedded within it, known as rhomboid proteases. When rhomboid proteases cut proteins, the split proteins are released from the membrane. From there, half a protein might go on to signal to another cell or both halves might end up being degraded to prevent further functioning. It all depends on the jobs of the specific proteins that are cut, which are known to play roles in everything from malaria to Parkinson’s disease.
Urban says they had already learned that rhomboid proteases have an unusual way of “deciding” which proteins to cut: They look for those whose structures are unstable. Since some proteins are inherently more stable or less stable, rhomboid proteases have certain “protein clients” that are more or less likely to be cut.
Building on the fact that cell membranes provide some support to proteins embedded in them, Urban tried changing the physical properties of this “habitat” to see if alterations would change which proteins rhomboid proteases cut.
He did that by treating human cells with two chemicals that either made the membranes more flexible or distorted their shape. As suspected, rhomboid proteases started cutting proteins they don’t normally cut, namely amyloid-beta precursor protein (APP) and the signaling protein Delta, while continuing to cut their standard “clients.” This suggests that the enzymes had lost their ability to discriminate between clients and non clients, or that non clients started acting like clients when the cell membrane changed, Urban says.
Aware that many drugs end up in the cell membrane, Urban assessed the effect of certain drugs on rhomboid proteases’ ability to recognize their normal clients.
Recent studies have looked at the ability of certain prescription-only NSAIDs to repair the function of gamma-secretase, another membrane enzyme that has more than 100 different protein clients, the most famous of which is APP. When gamma-secretase cuts APP at the “wrong” site, it generates a short protein piece that clumps in the brain and goes on to cause Alzheimer’s disease.
According to those same studies, some prescription-level NSAIDs, like flurbiprofen, approved for treating serious arthritis, make gamma-secretase less likely to cut APP at the wrong site, but how they do so is unclear.
If the drugs alter gamma-secretase activity by changing its habitat, the researchers thought they might have a similar effect on rhomboid proteases. So Urban treated the cells with flurbiprofen, indomethacin and sulindac at high but similar concentrations to those found in the blood of patients taking them at approved doses. Rhomboid proteases again cut clients they should not, like APP and Delta, just as they had when treated with the membrane-altering chemicals.
When cells were treated with NSAIDS sold over-the-counter, like aspirin, ibuprofen and naproxen, however, the range of clients cut by rhomboid proteases increased only slightly, if at all.
To test the effect of the NSAIDs on cell membranes directly, Urban used an instrument that measures melting temperatures. Because membranes are composed primarily of fat molecules, heat can make them more fluid, like melting butter. In the same way that olive oil is a liquid at room temperature but shortening is a solid, the composition of molecules in the cell membrane can raise or lower the temperature at which it “melts.” A lower melting temperature means a more flexible membrane, and the researchers found that the same prescription-level NSAIDs that lowered the membrane’s melting temperature caused rhomboid proteases to cut nonclient proteins.
“It’s possible that some of the side effects of NSAIDs are caused by their effect on the membrane and its enzymes,” says Urban. “Our results are also a caution to drug developers trying to target new drugs to the membrane or hoping to increase the duration or dosage of already approved drugs. Throwing off the balance of the membrane has consequences.”
One of the benefits of this study is that the researchers’ method can be used to test new drugs for membrane-altering effects. “Now we can use rhomboid proteases as predictors of a drug’s possible effects on the membrane and its enzymes,” says Urban.
DAUGHTERS PROVIDE AS MUCH ELDERLY PARENT CARE AS THEY CAN, SONS DO AS LITTLE AS POSSIBLE
From FMS Global News Desk of Jeanne Hambleton Embargoed: 19-Aug-2014 Source: American Sociological Association (ASA) Citations American Sociological Association Annual Meeting, Aug-2014
Newswise — SAN FRANCISCO — Parents are better off having daughters if they want to be cared for in their old age suggests a new study, which finds that women appear to provide as much elderly parent care as they can, while men contribute as little as possible.
“Whereas the amount of elderly parent care daughters provide is associated with constraints they face, such as employment or childcare, sons’ caregiving is associated only with the presence or absence of other helpers, such as sisters or a parent’s spouse,” said study author Angelina Grigoryeva, a doctoral candidate in sociology at Princeton University.
According to the study, daughters provide an average of 12.3 hours of elderly parent care per month as compared to sons’ 5.6 hours.
“In other words, daughters spend twice as much time, or almost seven more hours each month, providing care to elderly parents than sons,” said Grigoryeva, who will present her research at the 109th Annual Meeting of the American Sociological Association.
The study also indicates that in the division of elderly parent care among siblings in mixed-sex sibling groups, gender is the single most important factor in the amount of assistance each sibling provides.
“Sons reduce their relative caregiving efforts when they have a sister, while daughters increase theirs when they have a brother,” Grigoryeva said.
“This suggests that sons pass on parent caregiving responsibilities to their sisters.”
Grigoryeva’s paper relies on data from the 2004 wave of the University of Michigan Health and Retirement Study, a longitudinal panel study that surveys a nationally representative sample of more than 26,000 Americans over the age of 50 every two years.
In terms of the implications of her findings, Grigoryeva said the gender inequality in elderly parent care is particularly significant due to the consequences of elder care for caregivers.
“Numerous empirical studies report negative mental and physical health consequences, including a higher mortality rate, for people who provide care for elderly family members,” Grigoryeva said.
“In addition, these caregivers often have to balance elder care with employment, potentially resulting in career sacrifices and lower earnings. Providing care for elderly relatives can also impose significant financial burdens on caregivers in the form of direct expenses, as they often pay for goods and services for their care recipients.”
Considering that caregiving for elderly parents is disproportionately the responsibility of daughters, and previous research has shown women suffer from higher negative consequences associated with caregiving than men, the detrimental side-effects of caregiving for elderly parents could have “potentially intensifying effects on a series of gender inequalities pertaining to health and economic well-being,” Grigoryeva said.
Although, “the U.S. has been gradually becoming a more gender egalitarian society since the 1970s, my study shows gender inequality remains acute when it comes to elderly parent care,” Grigoryeva said.
About the American Sociological Association
The American Sociological Association (www.asanet.org), founded in 1905, is a non-profit membership association dedicated to serving sociologists in their work, advancing sociology as a science and profession, and promoting the contributions to and use of sociology by society.