Canadian researchers discover gene related to the appearance of aging

  • Author: Health Informer
  • Filed under: Health News
  • Date: Jul 16,2009

Scientists in Atlantic Canada have found a gene that may play a role in skin aging. Researchers were investigating the genetic cause of a rare disorder known as cutis laxa type 2 (CL2), which causes skin on the hands, feet and face to be loose and older looking, as well as growth and developmental delays including effects on the brain. In the process, researchers found some interesting correlations with the synthesis of proline, a chemical associated with skin and joint health.

The findings are published in the current online issue of American Journal of Human Genetics (www.cell.com/AJHG), and are part of the Atlantic Medical Genetic and Genomics Initiative (AMGGI), an ambitious, multi-partner gene-discovery project, managed by Genome Atlantic, and funded by Genome Canada/Genome Atlantic, Capital Health, IWK Health Centre, Dalhousie University, Nova Scotia Research Innovation Trust, Dalhousie Medical Research Fund, Nova Scotia Health Research Foundation and others as listed at www.amggi.ca.

Several Maritime Canadian families with CL2 were identified by clinicians at the IWK Health Centre’s Maritime Medical Genetics service. Through genomic research, scientists were able to identify the gene responsible for CL2 in these patients, citing an interruption of the metabolism of the amino acid, proline. The gene, pyrroline-5-carboxylate reductase 1, carries out the final step of proline synthesis.

Proline is a major component of connective tissue and skin proteins, collagen and elastin. It can be created by the body, and is also found in our diets. Some skin creams, cosmetics and vitamin supplements already include proline, touting its health benefits.

However, proline is not completely understood. Researchers know that it helps make ‘kinks’ in protein chains, critical for correct folding of these proteins. But it seems to play an independent role in protection from cellular stress. Proline made internally in our bodies may have a biological role distinct from that of dietary proline.

“This reinforces our understanding of proline as an integral part of skin health,” says Dr. Mark Samuels, AMGGI co-lead. “It provides the impetus for further work that could help us understand the development of skin, the largest, and one of the most complex organs of the body. It shows that you can’t mess with proline without causing a dramatic effect on many systems, including brain development.”

The gene is one of six novel discoveries made to date through the AMGGI project. Among them, a gene related to sudden cardiac death in Newfoundland and Labrador and one linked to haemoglobin production.

Source: Genome Atlantic


Study to be presented at the 2009 International Conference on Alzheimer’s Disease

Accera, Inc., a biotechnology company delivering breakthrough therapies in central nervous system diseases, announced further evidence for genetic interactions impacting the efficacy of the ketogenic compound AC-1202 (Axona(TM)) in Alzheimer’s disease. New data from the company’s previously completed double-blind, placebo-controlled trial in patients with mild-to-moderate Alzheimer’s disease demonstrates an interaction between two genetic markers that strongly influence the therapeutic response in patients. Dr. Samuel Henderson, Executive Director of Research, will present these results at the 2009 International Conference on Alzheimer’s Disease (ICAD) sponsored by the Alzheimer’s Association.

During this study, patients received daily administration of either AC-1202 or placebo for 90 days, with efficacy assessments performed at Baseline (Day 0), Day 45, Day 90 and after a two week washout from their assigned product on Day 104. In addition, analyses of a number of genotypic markers judged to be relevant to the physiological background of Alzheimer’s disease were also performed.

Previous analysis of the study revealed that patients administered AC-1202 who lacked the epsilon 4 variant of the APOE gene (E4(-)), demonstrated significant improvement from baseline values in the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) and improvement compared to placebo of 4.77 at Day 45 and 3.36 at Day 90 (p <0.05). ADAS-Cog, a neuropsychometric battery of tests that measures short-term memory and cognition, is probably the most widely used cognitive instrument used in clinical trials of anti-dementia drugs within the United States and Europe. Numerous clinical studies have demonstrated that modest improvements in ADAS-cog scores – on the order of 2 to 3 points over the course of a year – have been associated with significant cost reductions in overall managed care expenditures.

To further investigate pharmacogenomic responses of AC-1202 in AD, the effects of APOE4 carriage status and a polymorphism (IDE_7) in the insulin degrading enzyme gene (IDE) on ADAS-Cog scores were evaluated over the study course. In addition to degrading insulin, the Ide protein also degrades amyloid beta peptide and has been implicated in playing a role in Alzheimer’s disease.

In the population of patients who were both APOE4(-) and lacked the C/C polymorphism in IDE 7, more pronounced improvements in ADAS-cog scores than those previously reported were observed at each assessment time point (Day 45, 90 and 104). At Day 45 the improvement in ADAS-cog score was 4.18 (p=0.0004), while at Day 90 the difference was 4.73 (p=0.001). Of interest, a significant difference in cognitive test scores of 3.27 was observed two weeks after termination of AC-1202 treatment (p=0.034). This finding suggests that daily administration of AC-1202 may produce lasting effects in those patients with this combination of genotypic markers.

The combination of the E4(-); IDE_7(C/C)(-) genotype is prevalent in approximately 40% of the AD population, so the number of potential responder patients is substantial.

“This pharmacogenomic finding provides both insight into the mechanism of ketone-based therapies for Alzheimer’s disease, and also allows for the identification of patients who may respond best to therapy, ” said Dr. Samuel Henderson, Research Director at Accera. “This is the first scientific report of the role of IDE and its interaction with APOE on therapeutic efficacy in Alzheimer’s disease patients.”

The study results will be presented on Wednesday, July 15 under the title, “Evidence of an Interaction Between APOE and IDE in Ketone Body Therapies in Mild to Moderate Alzheimer’s Disease.” The conference is being held in Vienna, Austria at the Messe Wien Exhibition and Congress Center.

Axona is a first-in-class medical food for the clinical dietary management of the metabolic processes associated with mild-to-moderate Alzheimer’s disease. Dispensed by prescription, Axona targets the metabolic deficiencies and imbalances associated with Alzheimer’s disease by providing an alternative energy source for brain cells. With simple administration and once-a-day convenience, Axona is complementary to current Alzheimer’s disease therapies. For more information about Axona, please visit www.about-axona.com or ask your physician.

Alzheimer’s Disease

Alzheimer’s disease, the most common form of dementia, is a progressive and fatal disease for which there is no cure. In the United States, 5.2 million people are living with AD, and it has become the sixth leading cause of death. The disease attacks the brain’s cells, resulting in loss of memory, executive function and language skills.

AD significantly impacts millions of family members and other caregivers – mentally, physically and financially. The national Family Caregiver Alliance estimates that approximately 80 percent of caregivers provide unpaid assistance seven days a week. With the lack of innovative new medications for AD, both patients and caregivers are seeking alternatives to improve quality of life.


Music & Medicine: Unique Collaboration Combines Performing Arts and Science

  • Author: Health Informer
  • Filed under: Health News
  • Date: Jul 15,2009

When Eri Yoshimura begins to play, beautiful music fills the air. Her eyes close, and her body sways in time to the prelude. Her small hands glide over the keyboard gracefully, fluidly, as if they were tiny ballerinas on a miniature stage.

When she’s not performing, though, this University of North Texas (UNT) piano performance doctoral student is part of a collaborative study between the Denton campus and the UNT Health Science Center designed to measure the benefits to a pianist’s hands when using a special modified keyboard. This information can then be used to educate musicians who teach musicians and help prevent pianists — especially those with small hands — from developing pain caused by playing keyboards.

“We’re looking at hand function in piano players,” said Rita Patterson, PhD, professor and director of the Osteopathic Heritage Foundation Physical Medicine Core Research Facility (OHFPMCRF). “We’ve developed hardware and are collecting data on hand position and function while playing piano.”

The study is funded by the Joint Institutional Seed Research Program, an intramural grant designed to foster collaborative, innovative research conducted jointly by UNT and the UNT Health Science Center faculty — in this case Patterson; Shrawan Kumar, PhD, OHFPMCRF professor; and Kris Chesky, PhD, director of UNT’s Texas Center for Music and Medicine.

Yoshimura has studied piano-related pain among pianists in the past. She and Chesky published a paper in September 2006 concluding that 86 percent of college students majoring in piano experienced playing-related pain, with lack of flexibility and small hand span as contributors. This Joint Institutional Seed Research grant will allow PMI researchers to quantitatively measure what happens when a player sits down at a keyboard and begins to play.

One possible answer to alleviating the pain certain players feel while performing is the ergonomically modified Steinway piano that UNT students use in an effort to reduce such problems. The keyboard has narrower keys designed specifically for performers with smaller hands.

“We’re measuring hand size, hand position and how hard they’re hitting the keys,” Patterson said. “Our technology will give us a thorough motion analysis as [the student subject] plays. There are 30 students, and we’re gathering enough data to keep me busy for a long time. We can easily have two more dissertations’ worth of material.”

Patterson said the researchers are using sensors on the players’ hands that measure how far the hands must move to reach some of the chords common in piano pieces. Sensors under the piano keys measure how hard the player strikes the key while playing.

“We’re working on synching these systems properly,” Patterson said. “This will make the data easier to analyze.”

Yoshimura has played on the modified keyboard in the past — her first concert on the new piano, also the first at UNT, was a performance in 2006 of the complete 24 Preludes by French composer Claude Debussy.

“We are the first school to offer this [modified keyboard] to students,” Chesky said. “It’s a major departure from the norm and hugely significant because many people pursuing piano at the college level are Asian females. But this population has smaller hands than the average male, for whom standard pianos were designed.

“It’s like someone who is used to driving a 1987 Impala suddenly getting into a Ferrari. They just have much more flexibility and ease of playing. It’s really quite remarkable.”

Yoshimura, who came to UNT from Osaka, Japan, 10 years ago to pursue a second bachelor’s degree in music, a master’s degree and now a doctoral degree, said traditionally-sized keyboards do cause her pain.

“I have very small hands. When I span a chord or octave, I have to stretch my hands a lot, so I feel the tension in my arms,” Yoshimura said. “There are many pieces with big chords, so the repertoire I can play is limited.”

“Musicians are like athletes: they’re highly motivated, and they won’t tell you when they’re in pain,” Patterson said. “They just keep playing. Dr. Chesky has found that the repetitive use of certain muscles, hunching over, playing 24/7, causes musculoskeletal problems. We’ve partnered to look at this. Hopefully we’ll have a long history together.”

This dual-campus project has since grown, though, to include a third. George Kondraske, PhD, professor of electrical and biomedical engineering at the University of Texas at Arlington and founding director of UTA’s Human Performance Institute, is joining the investigation.

Patterson said she had heard of Chesky’s work with musicians, studies for which Kondraske had fashioned hardware.

“Dr. Kondraske modified what Dr. Chesky had to fit our needs,” she said. “Because we both have history with him, we’re rolling him into this project, and he will be included in any proposals for additional funding.”

Patterson said despite the distance between the three campuses, the study has proved to be a productive partnership.

“If you have competent people on each end, it works,” she said. “We’ve been to the Denton campus a couple of times to see the data collection. And e-mail’s great.”

The team hopes to continue this pilot program with more grants.

“We’ll probably have enough data with this initial study to publish, but it’s absolutely crucial that we expand this study and apply for federal funding,” she said.

Source: University of North Texas Health Science Center


A new Mayo Clinic study found that the clinical criteria for mild cognitive impairment is better at predicting who will develop Alzheimer’s disease than a single memory test. This is one more piece of information to aid in the identification and early treatment of individuals most likely to develop Alzheimer’s disease. This study will be presented at the Alzheimer’s Association International Conference on Alzheimer’s Disease on July 14 in Vienna.

Alzheimer’s disease is a degenerative disorder of the brain in which nerve cells die over time, resulting in a steady loss of memory and other thinking abilities. An estimated 5.3 million Americans are living with Alzheimer’s disease, and it is the sixth-leading cause of death in the U.S. Mild cognitive impairment is a transitional state between normal aging and the earliest features of Alzheimer’s disease.

“The goal of this research is to try to predict who is going to develop Alzheimer’s disease in the future,” says Ronald Petersen, M.D., Ph.D., a neurologist at Mayo Clinic and the lead author of this study. “Ideally, we’d like to identify individuals before any damage is done in the brain. The sooner we intervene on this process with medications or other therapies, the greater impact we can have on lessening the number of people who will ultimately develop Alzheimer’s disease.”

Dr. Petersen and his team studied 1,261 individuals aged 70-89 years who were cognitively normal or had only slight memory impairment at the onset of the study. The individuals were followed for up to 10 years. Scores on a memory test and the clinical criteria for mild cognitive impairment (including a memory test as well as other assessments of cognitive function) were studied as possible predictors for eventual development of Alzheimer’s disease. The team found that the clinical criteria for mild cognitive impairment was better able to predict who was going to develop Alzheimer’s disease in the future.

“As the baby boomers age into the period of risk for Alzheimer’s disease, we’re talking about a significant number of individuals who may become cognitively impaired in the very near future,” says Dr. Petersen. “Consequently, we need information like this about the best methods of early prediction so that we can develop therapies to prevent or treat the condition and avoid being overwhelmed by the burden of these individuals on the health care system.”

Other members of the Mayo Clinic research team included David Knopman, M.D.; Bradley Boeve, M.D.; Ruth Cha; V. Shane Pankratz, Ph.D.; Yonas Geda, M.D.; Rosebud Roberts, M.B.Ch.B.; and Clifford Jack, M.D.


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