Health Reform – Where Are We Now? – American Geriatrics Society

It’s been one-year since President Obama signed the Affordable Care Act into law, which includes important provisions that are helping millions of older Americans and will continue to improve older adult healthcare. The Affordable Care Act addresses many issues that AGS has advocated for and includes provisions that will enhance the geriatrics and primary care workforce; support care coordination; establish training programs for direct-care workers and family caregivers, and provide long-term care services and supports options.

As described in the law, the Administration has established several commissions/panels/advisory boards, which have the potential to impact and shape geriatrics and quality healthcare for older Americans. These include:

National Health Care Workforce Commission

Our nation faces an impending geriatrics workforce crisis as the number of older patients with complex health needs outpaces the number of health care providers with the knowledge and skills to care for them. The Commission has an opportunity to advance fundamental changes to ensure that older adults have access to the high-quality care they need.

Patient Centered Outcomes Research Institute

For geriatrics, breakthroughs in research can lead to the development of policies that will help older Americans, especially those with multiple chronic illnesses, lead healthier and more productive lives. AGS leader Mary Tinetti, MD, was appointed to the Methodology Committee of the Patient Centered Outcomes Research Institute.

The Center for Medicare and Medicaid Innovation

We believe the Center’s work holds great promise for developing and replicating models that will improve the delivery and quality of care to older adults while potentially reducing costs to the Medicare program. AGS leader Chad Boult, MD, MPH, MBA has been named Senior Policy Advisor for the Center.

Federal Coordinated Health Care Office

This office has potential to assure that there are leverage points to coordinate and integrate care and to promote plans that work cost effectively for Medicare and Medicaid eligible beneficiaries.

AGS has commented on a number of provisions to be implemented as part of the Affordable Care Act including:

– Criteria for new Models of Care to be tested

– Incentive Payments for Primary Care Services

– Development of the Physician Compare Website

– Medicare Fraud and Abuse Provisions

– Graduate Medical Education (GME) and Preventive Services Provisions

– Development of guidance concerning Health Risk Assessments (HRAs)

We thank you for your various points of engagement and participation as we worked last year to see that geriatric and aging related provisions would be included and for the help of many of you in the issues that have come up for input this past year and will undoubtedly come our way this year as we work to assure the importance of quality and safe care for our country’s older adults.

Source:

American Geriatrics Society

Muscle Stem Cell Transplant Boosts Diseased Muscle Function And Replenishes Stem Cell Pool

Researchers at the Joslin Diabetes Center have demonstrated for the first time that transplanted muscle stem cells can both improve muscle function in animals with a form of muscular dystrophy and replenish the stem cell population for use in the repair of future muscle injuries.

“I’m very excited about this,” said lead author Amy J. Wagers, Ph.D., Principal Investigator in the Joslin Section on Developmental and Stem Cell Biology, principal faculty member at the Harvard Stem Cell Institute and Assistant Professor of Stem Cell and Regenerative Biology at Harvard University. “This study indicates the presence of renewing muscle stem cells in adult skeletal muscle and demonstrates the potential benefit of stem cell therapy for the treatment of muscle degenerative diseases such as muscular dystrophy.”

The study was designed to test the concept that skeletal muscle precursor cells could function as adult stem cells and that transplantation of these cells could both repair muscle tissue and regenerate the stem cell pool in a model of Duchenne muscular dystrophy, she said. The research is published in the July 11 issue of Cell.

Duchenne muscular dystrophy is the most common form of the disease and is characterized by rapidly progressing muscle degeneration. The disease is caused by a genetic mutation and there is currently no cure.

The data from this new study demonstrate that regenerative muscle stem cells can be distinguished from other cells in the muscle by unique protein markers present on their surfaces. The authors used these markers to select stem cells from normal adult muscle and transferred the cells to diseased muscle of mice carrying a mutation in the same gene affected in human Duchenne muscular dystrophy.

“Once the healthy stem cells were transplanted into the muscles of the mice with muscular dystrophy, they generated cells that incorporated into the diseased muscle and substantially improved the ability of the treated muscles to contract,” said Wagers. “At the same time, the transplantation of the healthy stem cells replenished the formerly diseased stem cell pool, providing a reservoir of healthy stem cells that could be re-activated to repair the muscle again during a second injury.”

According to the paper, these cells provide an effective source of immediately available muscle regenerative cells as well as a reserve pool that can maintain muscle regenerative activity in response to future challenges.

“This work demonstrates, in concept, that stem cell therapy could be beneficial for degenerative muscle diseases,” Wagers said.

Wagers also said the study will lead to other studies in the near-term that will identify pathways that regulate these muscle stem cells in order to figure out ways to boost the normal regenerative potential of these cells. These could include drug therapies or genomic approaches, she said. In the long-term, the idea will be to replicate these findings in humans.

“This is still very basic science, but I think we’re going to be able to move forward in a lot of directions. It opens up many exciting avenues,” she said.

The Wagers Lab at Joslin studies both hematopoietic stem cells, which constantly maintain and can fully regenerate the entire blood system, as well as skeletal muscle stem cells, involved in skeletal muscle growth and repair. The work is aimed particularly at defining novel mechanisms that regulate the migration, expansion, and regenerative potential of these two distinct adult stem cells.

This study was funded by in part by a Burroughs Wellcome Fund career award, Seed and Program Grants from the Harvard Stem Cell Institute and grants from Jain Foundation, Beckman Foundation, and the National Institutes of Health.

Others participating in the research were Massimiliano Cerletti, Sara Jurga and Jennifer L. Shadrach of the Joslin Section on Developmental and Stem Cell Biology and the Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute; and Carol A. Witczak, Michael F. Hirshman and Laurie J. Goodyear of the Joslin Section on Metabolism.

About Joslin Diabetes Center

Joslin Diabetes Center is the world’s largest diabetes clinic, diabetes research center and provider of diabetes education. Joslin is dedicated to ensuring people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure for the disease. Founded in 1898 by Elliott P. Joslin, M.D., Joslin is an independent nonprofit institution affiliated with Harvard Medical School

Joslin Diabetes Center
One Joslin Pl.
Boston, MA 02215
United States
joslin

90% Of People Over Age 65 Have Prescription Drug Coverage, Many Enrolled In Medicare Benefit Concerned About Future Coverage, Study Says

More than 90% of U.S. residents ages 65 and older have some form of prescription drug coverage, in part because of enrollment in the Medicare prescription drug benefit, according to a study published Tuesday on the Health Affairs Web site, the Miami Herald reports (Hatcher, Miami Herald, 8/1). For the study, Daniel McFadden, a professor of economics at the University of California-Berkeley, and colleagues surveyed 1,571 seniors. About two million seniors who took at least one medication monthly and would benefit from the Medicare prescription drug benefit had not enrolled, according to the study (Lee, Washington Post, 8/1). The study finds that enrollment rates in the Medicare prescription drug benefit were lowest among healthy seniors, low-income seniors, widows, unmarried female seniors and seniors with low education levels (Miami Herald, 8/1). According to the study, about 40% of low-income seniors without a college education did not have prescription drug coverage. Only 11.3% of seniors with annual incomes of more than $20,000 did not have prescription drug coverage, the study finds. In addition, the study finds that seniors who took fewer medications were less likely to have prescription drug coverage than those who took more treatments. Only 5.2% of seniors who took three or more medications did not have prescription drug coverage, the study finds. The study attributes the results to “constraints or perceptions that make it difficult” for low-income seniors and those with low education levels to “account for future benefits.” The study recommends the elimination the financial penalty for late enrollment in the Medicare prescription drug benefit to attract more seniors to the program and counseling targeted at healthy low-income seniors to inform them of the potential benefits of prescription drug coverage (Freking, Long Island Newsday, 8/1).

Opinions of Rx Drug Benefit
The study also examines opinions of seniors about the Medicare prescription drug benefit. According to the study, 58% of seniors considered the Medicare prescription drug benefit a “major benefit,” and 30% praised the design of the program. However, 77% of seniors said that the Medicare prescription drug benefit should automatically enroll beneficiaries, and 88% consider the “doughnut hole” coverage gap a “significant drawback” of the program, the study finds. The Post also examined the findings of a survey of seniors released last week by the Kaiser Family Foundation (Washington Post, 8/1). The tracking survey found that more than eight in 10 seniors who are enrolled in Medicare drug plans are satisfied with their plans, while nearly two in 10 who have used their plans report experiencing a major problem with them (

Stroke Patients At Greater Risk For Falls

Stroke patients are at high risk for falls and subsequent injuries after leaving the hospital, but prevention programs may reduce this risk, New Zealand researchers reported in Stroke: Journal of the American Heart Association.

“People who have had a stroke fall almost twice as often as people who haven’t had a stroke,” said Ngaire Kerse, Ph.D., lead author of the study and associate professor in the Department of General Practice and Primary Healthcare at the School of Population Health in the University of Auckland, New Zealand. “Falls are very common and risk factors for falls are easy to identify. We need to emphasize fall prevention during stroke services when patients resettle at home.”

In a study of 1,104 stroke survivors, 37 percent reported at least one fall during the six months after their stroke. Of the 407 participants who fell, 37 percent sustained an injury that required medical treatment and 8 percent sustained a fracture.

About half of the stroke patients who fell only fell once, but 12 percent fell more than five times. More than three-fourths (77 percent) of the stroke patients fell at home. Of the 93 patients who fell away from home, 42 fell indoors.

“This is much higher than reported previously,” Kerse said. “The incidence of falls in the study is even higher than for older people in long-term residential care.”

Researchers also found:
Older age, a prior fall, previous stroke, prior dependency before stroke, poor cognitive status and low mood such as depression were associated with either a higher risk of falls or injury after stroke.

Women were more likely to sustain injury than men.

Those who fell in the year prior to stroke were 1.6 times more likely to fall after stroke.

Participants who were more dependent were twice as likely to fall after stroke.

Those with higher levels of functioning were 80 percent less likely to sustain injury after stroke.

Those who were depressed were almost 1.5 times as likely to fall as those who weren’t.

Researchers in the Auckland Regional COmmunity Stroke (ARCOS) study followed stroke patients from 2002-03 to determine if any falls had occurred. A trained research nurse interviewed the patients after stroke onset and at one and six months post stroke. The patients were scored based on the Barthel index as independent, intermediate or dependent. The Barthel index measures the ability to get up, walk, transfer from bed or a chair, dress and other general activities of daily living.

Prior to stroke, 30 percent of the participants had fallen, with 37 percent of those who reported a fall in the six months after stroke also reporting they had fallen prior to stroke.

Researchers said participants who had a higher score for overall activity before the stroke were at less risk of injury after the stroke.

“Falls are important for all older people,” Kerse said. “But in people with stroke, falls add to the consequences of stroke. There is an opportunity to offer fall prevention strategies as part of the initial rehabilitation for stroke patients and as part of ongoing rehabilitation in the home.”

Researchers suggest prevention programs include lower leg strengthening and balance retraining as well as exercise programs. Home hazard assessment and modification should include appropriate lighting, removing obstacles and installing transfer rails. These are proven fall prevention strategies. Family members also need to be involved in making modifications and taking action that will help prevent falls.

“We need to increase the awareness among family members on fall prevention,” Kerse said. “More than one-third of patients after stroke will fall and the consequences can be disastrous. Our findings emphasize the need to incorporate fall prevention strategies into stroke services.”

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Co-authors are: Varsha Parag, M.Sc.; Valery L. Feigin, Ph.D.; Craig S. Anderson, Ph.D.; Maree L. Hackett, Ph.D.; and Derrick A. Bennett, Ph.D.

The study was funded by the New Zealand Health Research Council.

For more information on stroke, visit the American Stroke Association Web site: strokeassociation/.

Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.

NR08 – 1062 (Stroke/Kerse)

Source: Bridgette McNeill

American Heart Association

Time For Aged Care To Come Out Of The ‘Policy Inertia Zone’

The Australian Medical Association urged the Government to address the policy inertia that continued to restrict medical services for the care of sick and frail residents of aged care homes.

AMA President, Dr Rosanna Capolingua, warned that GP services to residents in aged care homes were under growing pressure.

She said GPs were continually frustrated by the barriers that prevented constant medical care from being delivered to residents of aged care homes.

As part of General Practice Week, the peak medical body is calling for the Federal Government to bring aged care out of the ‘policy inertia zone’ as the medical needs of older Australians became more complex and numerous.

“Successive governments have done little to actively involve medical care in the daily operations of aged care homes – it’s time for the Government to take action,” Dr Capolingua said.

“We need to see policies that will effectively bring medical care to frail and sick residents in a timely and suitable manner.

“Older Australians should continue to have access to a range of quality medical services – as it’s a time in their lives when they need them most.”

The AMA is calling for aged care policies that:

- Introduce dedicated Medicare payments that improve access to GPs and medical specialists for older Australians;

- Enable more GPs to use general practice nurses to assist in the delivery of care in residential and community settings;

- Increase recurrent funding for community and residential aged care to meet the real costs of care;

- Adopt strategies that lead to wage parity between the acute and aged care sectors to encourage skilled nurses back into the sector with the capacity to deliver quality aged care services; and

- Improve clinical management and the delivery of care in the residential aged care sector by introducing computer systems that facilitate medical records and prescribing, and which connect the GP to the residential aged care facility and the pharmacy.

Australian Medical Association

Resistance Training Programs Appear To Improve Some Cognitive Skills In Older Women

One year of once- or twice-weekly resistance training appears to improve attention and conflict resolution skills among older women. Teresa Liu-Ambrose, Ph.D., P.T., of Vancouver Coastal Health Research Institute and University of British Columbia, Vancouver, Canada, and colleagues studied 155 women age 65 to 75. Participants were randomly assigned to participate in resistance training once (54 women) or twice (52 women) weekly, whereas 49 women in a control group participated in twice-weekly balance and tone training.

After one year, women in both resistance training groups significantly improved their scores on tests of selective attention (maintaining mental focus) and conflict resolution. The program simultaneously improved muscular function in the women.

“This has important clinical implications because cognitive impairment is a major health problem that currently lacks a clearly effective pharmaceutical therapy and because resistance training is not widely adopted by seniors,” the authors write. “The doses of resistance training we used in this study fall within those recommended by the 2008 Physical Activity Guidelines for seniors.”

Arch Intern Med. 2010;170[2]:170-178.

Source
Archives of Internal Medicine

OxThera: Pivotal Study Is Being Conducted With Oxabact(TM) For The Treatment Of Primary Hyperoxaluria

OxThera announced that all 42 patients have been enrolled in their pivotal phase II/III study using Oxabact™ for the treatment of Primary Hyperoxaluria. Results from this multicenter study will be presented during Q4 of 2008 and be used to file for licensure in EU, US and the rest of the world.

Primary Hyperoxaluria is a rare genetic disease in which excessive oxalate is produced by the liver and excreted in the urine by the kidneys. High levels of urinary oxalate cause kidney stones and/or calcification of the kidney which could lead to kidney failure and in many cases premature death. OxThera estimates that there are about 2000 patients with Primary Hyperoxaluria in EU and US combined.

Oxabact™ consists of a unique intestinal bacterium, Oxalobacter formigenes, naturally colonizing the intestinal tract of most humans with the purpose to degrade oxalate. Previous studies with Oxabact™ have already shown a significant effect in lowering urinary oxalate which in turn leads to a decreased risk of kidney damage. Oxabact™ has been designated orphan drug status in both EU and the US.

The 28 week pivotal study is a randomized, double-blind, placebo-controlled, multi-center study being conducted at eight Primary Hyperoxaluria referral sites in the Netherlands, France, UK, Germany and US.

“Primary Hyperoxaluria is a very serious disease often leading to early kidney failure and in particular systemic oxalate deposition with all its complications including death with no effective medical therapy currently available. For majority of patients the only real option today is a combined liver-kidney transplantation which is available to a very limited number of patients worldwide. Therefore, the Primary Hyperoxaluria community has great hopes that Oxabact™ will offer a new treatment opportunity. A confirmation of earlier study results with Oxabact™ will reflect scientific breakthrough and a new chapter in the treatment of this rare and severe disease”, says Prof. Bernd Hoppe, University Hospital in Cologne, Germany.

Jon Heimer, CEO and President of OxThera comments: “After several years of intensive research on Oxalobacter formigenes and Oxabact™, a significant milestone is met with the inclusion of all patients in this pivotal study. A successful outcome will put us in a position to file for licensure and making the product available to treating physicians and patients during 2009 which is very exciting”.

Short facts about OxThera

OxThera is a biotechnology company active in the development of products for the treatment of metabolic disorders resulting from excess levels of oxalate from endogenous and exogenous sources. Currently, OxThera has two products in its pipeline, Oxabact™ for the treatment of primary hyperoxaluria, and Oxazyme™, for the prevention of recurring calcium-oxalate kidney stones due to secondary hyperoxaluria.

Oxalate is a metabolic end product in humans. It is endogenously produced by the liver and also derived by absorption from the diet. The majority of oxalate is eliminated from the body through the kidneys and a small percentage is eliminated through the GI-tract. Oxalate forms a calcium-oxalate salt which is insoluble at physiological pH and its accumulation can result in serious renal conditions. Consistent high levels of urinary oxalate are known as “hyperoxaluria”, which can result in recurrent kidney stones and renal complications. Hyperoxaluria is currently classified as:

- Primary hyperoxaluria types I and II are rare genetic diseases resulting from overproduction of oxalate in the liver (PH I) or in all body cells (PH II); urinary oxalate excretion is usually greater than 100 mg/day (normal level

JCI Online Early Table Of Contents: Oct. 9, 2008

VASCULAR BIOLOGY: A real-time view of blood flow through the pancreas

A team of researchers at Vanderbilt University, Nashville, has developed a new microscopy approach that enabled them to image, in real time, the flow of blood in mouse pancreatic islets of Langerhans.

The pancreatic islets of Langerhans have a central role in regulating the amount of glucose in the blood. Beta cells are found in the center of the islets and produce insulin, which decreases levels of glucose in the blood. They are surrounded by non-beta cells, which produce a number of other hormones, including glucagon, which increases levels of glucose in the blood. The team of researchers, led by David Piston and Alvin Powers, was able to reconstruct the in vivo 3D architecture of mouse islets and observe real-time blood flow. Two main blood-flow patterns were observed: inner-to outer, in which blood first contacted the beta-cells and then the non-beta cells, and top-to-bottom, in which blood moved from one side of the islet to the other regardless of cell type. These data have important implications for our understanding of how blood glucose levels are regulated by the cells in the pancreatic islets of Langerhans. In addition, the authors hope that this approach can be used to study blood flow in the other organs.

TITLE: Real-time, multidimensional in vivo imaging to investigate blood flow in mouse pancreatic islets

AUTHOR CONTACT:
David W. Piston
Vanderbilt University, Nashville, Tennessee, USA.

Alvin C. Powers
Vanderbilt University, Nashville, Tennessee, USA.

View the PDF of this article at: https://www.the-jci/article.php?id=36209

BONE BIOLOGY: The protein NFATc1: a master controller of bone destruction

The most common disease caused by excessive bone destruction is osteoporosis. However, regional bone loss is observed in several inflammatory conditions, including cherubism and rheumatoid arthritis. Laurie Glimcher and colleagues, at Harvard School of Public Health, Boston, have now provided new insight into the molecular control of bone degradation in mice during growth and disease, thereby uncovering a potential new therapeutic target for these diseases.

In the study, mice in which expression of the protein NFATc1 was eliminated at 10 days old developed osteopetrosis (a condition in which the bones are harder and denser than normal). This was associated with a decrease in the number of cells that destroy bone (osteoclasts). Further analysis revealed that NFATc1 regulated expression of numerous genes required for osteoclast generation. Additional experiments showed that elimination of NFATc1 in a mouse model of cherubism prevented bone loss, although it did not lessen the associated inflammation. The authors therefore conclude that NFATc1 is necessary for generating osteoclasts in growing and adult mice and might be a new therapeutic target for bone loss associated with inflammatory conditions such as cherubism.

TITLE: NFATc1 in mice represses osteoprotegrin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism

AUTHOR CONTACT:
Laurie H. Glimcher
Harvard School of Public Health, Boston, Massachusetts, USA.

View the PDF of this article at: https://www.the-jci/article.php?id=35711

MUSCLE BIOLOGY: Slow, slow, quick, quick, slow: molecular insight into muscle fiber composition

Muscles are made of two different types of fibers: fast-twitch fibers, which contract quickly and powerfully, tire easily, and are suited to physical exercise such as weight lifting and sprinting; and slow-twitch fibers, which can contract for long periods of time, generate less power, and are suited to endurance events. The relative amount of each type of fiber in a muscle can change over time, allowing a muscle to adapt to changing physical demands. New insight into the molecules that control the relative amount of slow- and fast-twitch fibers in the muscles of mice has now been provided by a team of researchers at the University of Heidelberg, Germany, and the University of Texas Southwestern Medical Center, Dallas.

The researchers, led by Norbert Frey and Eric Olson, found that mice lacking the protein calsarcin-2, which is expressed exclusively by fast-twitch muscle, have substantially reduced body weight, reduced amounts of fast-twitch muscle, and increased ability to run long distances. Consistent with the improved performance in distance running, muscles of the calsarcin-2-deficient mice showed a switch toward slow-twitch fibers. Further analysis revealed a molecular mechanism for this change in the fiber-type composition of the muscles: increased activity of the calcineurin/NFAT signaling pathway, which is known to promote the formation of slow-twitch fibers. The authors therefore conclude that calsarcin-2 modulates mouse exercise performance by dampening calcineurin/NFAT signaling and thereby reducing the formation of slow-twitch muscle fibers.

TITLE: Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/NFAT activation

AUTHOR CONTACT:
Norbert Frey
University of Heidelberg, Heidelberg, Germany.

Eric N. Olson
University of Texas Southwestern Medical Center, Dallas, Texas, USA.

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View the PDF of this article at: https://www.the-jci/article.php?id=36277

TRANSPLANTATION: Engineering Tregs to see transplants and stop rejection

Immune cells known as Tregs are regulatory cells that dampen immune responses and prevent the immune system attacking the body’s own tissues. It has been suggested that it might be possible to generate Tregs specifically to dampen immune responses that cause rejection of transplanted organs from donors not genetically identical to the transplant recipient. Mouse Tregs able to suppress rejection of hearts transplanted between genetically disparate donors and recipients have now been generated by Robert Lechler and colleagues, at King’s College London, United Kingdom.

Tregs that directly recognized one of the main targets on the heart transplant of the destructive immune response were obtained from the intended recipient mice. These cells were then engineered so that they also indirectly recognized this target. When infused into the recipient mice, Tregs able to both directly and indirectly recognize the main target of the destructive immune response were better at preventing rejection of heart grafts than Tregs able to only directly recognize this target. The authors therefore suggest that it might be possible to engineer Tregs to be clinically useful in transplantation settings.

TITLE: Conferring indirect allospecificity on CD4+CD25+ Tregs by TCR gene transfer favors transplantation tolerance in mice

AUTHOR CONTACT:
Robert Lechler
King’s College London, London, United Kingdom.

View the PDF of this article at: https://www.the-jci/article.php?id=33185

ONCOLOGY: Of cancer and metabolic disease: a role for the protein S6K1 in distinguishing between the two

Beta-cells in the pancreatic islets of Langerhans are dysfunctional in individuals with diabetes, and the molecules that control their growth and function are therefore potential therapeutic targets. While determining the role of the protein Akt1 in regulating the growth and function of mouse pancreatic beta-cells, Mario Pende and colleagues, at INSERM U845, France, generated data that might have more of an impact on anticancer therapy.

In the study, although mice engineered to overexpress a constitutively active form of Akt1 in their pancreatic beta-cells showed improved beta-cell function (because the cells were enlarged), a substantial number of the mice developed insulinomas (a rare form of pancreatic cancer) later in life and died. Further analysis revealed that the signaling protein S6K1 was required for constitutively activated Akt to cause insulinoma formation but not required for it to increase pancreatic beta-cell size. These data have implications for the development of strategies to modify pancreatic beta-cell size and function while minimizing cancer risks as well as suggesting that S6K1 might be a useful therapeutic target for individuals with some forms of cancer.

TITLE: Constitutively active Akt1 expression in mouse pancreas requires S6 kinase 1 for insulinoma formation

AUTHOR CONTACT:
Mario Pende
INSERM U845, Paris, France.

View the PDF of this article at: https://www.the-jci/article.php?id=35237

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Source: Karen Honey

Journal of Clinical Investigation

View drug information on Glucagon.

Brain Development Goes Off Track As Vulnerable Individuals Develop Schizophrenia

Two new research studies published in Biological Psychiatry point to progressive abnormalities in brain development that emerge as vulnerable individuals develop schizophrenia.

The first of these papers studied individuals with a deletion of a small section of chromosome 22. This genetic deletion often results in the development of abnormalities in the structure of the heart and of the face, a condition called velocardiofacial syndrome (VCFS; also known as 22q11.2 deletion syndrome). Up to 32% of people with VCFS develop psychotic disorders including schizophrenia, which occurs in 1% of the general population.

Using magnetic resonance imaging (MRI), Dr. Wendy Kates and her colleagues showed that during adolescence, progressive deficits in the volume of the temporal cortex gray matter were predictive of developing psychosis.

“Our findings suggest that in VCFS, brain changes during mid-adolescence, particularly in the temporal lobe, predict early signs of psychosis,” said Dr. Kates. “This suggests that it may be possible, eventually, to develop a screening tool that would identify those VCFS-affected youth who are at the highest risk for schizophrenia.”

In another paper, Dr. Andrew McIntosh and colleagues report a similar pattern among adolescents and young adults who were followed over a 10 year period. All of the young people were well at the beginning of the study, but some were at high genetic risk of developing schizophrenia due to having family members with schizophrenia.

“The participants were examined repeatedly by a psychiatrist and with structural brain scans to see if there were changes in brain structure in people who later became unwell,” explained Dr. McIntosh. “At the end of the study, we found that there were accelerated reductions in the volume of particular brain structures in the people at high risk, and additional reductions in the volume of the frontal lobes in those people who later developed schizophrenia.”

These two studies highlight the existence of progressive changes in brain structure related to the emergence of symptoms among individuals at risk for developing schizophrenia.

“These studies cannot define the specific changes at the cellular level and thus, we are limited in our capacity to make precise predictions based on these MRI data,” commented Dr. John Krystal, Editor of Biological Psychiatry. “However, the findings suggest that schizophrenia is not simply a ‘scar’ but rather an ongoing brain process that might need to reach an as yet unclear stage where symptoms emerge. That being the case, there is hope that someday one might develop treatments that block this ‘disease process’ as we have been able to do for some other heritable brain diseases.”

Source: Elsevier, AlphaGalileo Foundation.

Scientists Demonstrate Feasibility Of Preventing Malaria Parasite From Becoming Sexually Mature

Discovery could help to control the spread of drug resistance

Researchers have demonstrated the possibility of preventing the human malaria parasite, Plasmodium falciparum, which is responsible for more than a million malaria deaths a year, from becoming sexually mature.

The discovery could have implications for controlling the spread of drug resistance, which is a major public health problem and which hinders the control of malaria.

The life cycle of Plasmodium falciparum is complex, and it is not yet known what triggers the production of parasite gametes or sex cells. These sexual forms of the parasite do not contribute to malaria symptoms, but are essential for transmission of malaria between humans via the bite of a mosquito.

A team based at the London School of Hygiene & Tropical Medicine, working with a colleague from the Wellcome Trust Sanger Institute in Cambridge, identified a parasite enzyme that is instrumental in triggering the emergence of mature gametes within the mosquito. Their findings are published today in the journal PLoS Biology.

Dr. David A Baker, a Reader in Parasite Molecular Biology at the London School of Hygiene & Tropical Medicine and senior author of the study, comments: ‘The enzyme we have discovered, a protein kinasea, is essential for the development of malaria parasite gametes. Working with genetically modified parasites, in combination with inhibitors of this enzyme, we have demonstrated that it is feasible to block the sexual stage of the life cycle of the malaria parasite.

He adds: ‘This has exciting implications in terms of improving how we go about tackling malaria. If a drug can be developed that targets this stage of the life cycle, and combined with a curative drug, it would be an important new approach for controlling malaria transmission and the spread of drug resistance’.

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