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Posts Tagged ‘Down syndrome’


Studying Alzheimer’s biomarkers in Down syndrome

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

NIH supports new studies to find Alzheimer’s biomarkers in Down syndrome

Groundbreaking initiative will track dementia onset, progress in Down syndrome volunteers

http://www.nih.gov/news-events/news-releases/nih-supports-new-studies-find-alzheimers-biomarkers-down-syndrome

 

The National Institutes of Health has launched a new initiative to identify biomarkers and track the progression of Alzheimer’s in people with Down syndrome. Many people with Down syndrome have Alzheimer’s-related brain changes in their 30s that can lead to dementia in their 50s and 60s. Little is known about how the disease progresses in this vulnerable group. The NIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiative will support teams of researchers using brain imaging, as well as fluid and tissue biomarkers in research that may one day lead to effective interventions for all people with dementia.

The studies will be funded by the National Institute on Aging (NIA) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of NIH. The institutes are jointly providing an estimated $37 million over five years to two highly collaborative projects, which enlist a number of leading researchers to the effort. To advance Alzheimer’s research worldwide, the teams will make their data and samples freely available to qualified researchers.

“This is the first large-scale Alzheimer’s biomarker endeavor to focus on this high-risk group,” said Laurie Ryan, Ph.D., chief of the Dementias of Aging Branch in NIA’s Division of Neuroscience, which leads NIH research on Alzheimer’s.  “Much like the long-established Alzheimer’s Disease Neuroimaging Initiative, the goal of this initiative is to develop biomarker measures that signal the onset and progression of Alzheimer’s in people with Down syndrome. Hopefully, one day, we will also use these biomarkers to determine the effectiveness of promising treatments.”

The link between Alzheimer’s and Down syndrome is well-known. People with Down syndrome are born with an extra copy of chromosome 21, which contains the amyloid precursor protein gene. This gene plays a role in the production of harmful amyloid plaque, sticky clumps that build up outside neurons in Alzheimer’s disease. Having three copies of this gene is a known risk factor for early-onset Alzheimer’s that can occur in people in their 30s, 40s and 50s. By middle age, most but not all adults with Down syndrome develop signs of Alzheimer’s, and a high percentage go on to develop symptoms of dementia as they age into their 70s.

The initiative establishes funding for two research teams that will pool data and standardize procedures, increase sample size, and collectively analyze data that will be made widely available to the research community. The teams will employ an array of biomarkers to identify and track Alzheimer’s-related changes in the brain and cognition for over 500 Down syndrome volunteers, aged 25 and older. The measures include:

  • Positron emission tomography (PET) scans that track levels of amyloid and glucose (energy used by brain cells); MRI of brain volume and function; and levels of amyloid and tau in cerebrospinal fluid and blood;
  • Blood tests to identify biomarkers in blood, including proteins, lipids and markers of inflammation;
  • Blood tests to collect DNA for genome-wide association studies that identify the genetic factors that may confer risk, or protect against, developing Alzheimer’s;
  • Evaluations of medical conditions and cognitive and memory tests to determine levels of function and monitor any changes;
  • For the first time in people with Down syndrome, PET brain scans that detect levels of tau, the twisted knots of protein within brain cells that are a hallmark Alzheimer’s disease.

Aside from earlier onset, Alzheimer’s in people with Down syndrome is similar to Alzheimer’s in others. The first symptom may be memory loss, although people with Down syndrome initially tend to show behavior changes and problems with walking.

“Over the past 30 years, the average lifespan of people with Down syndrome has doubled to 60 years—a  bittersweet achievement when faced with the possibility of developing Alzheimer’s,” said Melissa Parisi, M.D., Ph.D., chief of the NICHD Intellectual and Developmental Disabilities Branch, which leads NIH’s Down syndrome research. “There is much to learn about Alzheimer’s in Down syndrome, and we’re hopeful that these new projects will provide some answers. One mystery we hope to solve is whether or not the disease progresses at a faster rate in this group.”

Parisi noted that research into Alzheimer’s in Down syndrome is a key focus of the National Plan to Address Alzheimer’s Disease(link is external), which calls for improved care for specific populations that are unequally burdened by the disease, including people with Down syndrome, and for increased research that may lead to possible Alzheimer’s therapies.

Benjamin Handen, Ph.D., Department of Psychiatry, University of Pittsburgh, heads a team that involves investigators and data from: Banner Alzheimer’s Institute, Phoenix; Cambridge University, England; Alzheimer’s Disease Cooperative Study, San Diego; Laboratory of Neuro Imaging, University of Southern California, Los Angeles. Nicole Schupf, Ph.D., Columbia University Medical Center, New York City, leads a team involving investigators at: University of California, Irvine; Kennedy Krieger Institute/Johns Hopkins University, Baltimore; Massachusetts General Hospital/Harvard University, Boston; and the University of North Texas Health Sciences Center, Fort Worth.

Learn more about this topic at https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-people-down-syndrome.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s website at http://www.nichd.nih.gov.

About the National Institute on Aging: The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. It provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer’s Disease Education and Referral (ADEAR) Center at www.nia.nih.gov/alzheimers.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

 

 

NATIONAL PLAN TO ADDRESS ALZHEIMER’S DISEASE: 2015 UPDATE

pdf-document/national-plan-address-alzheimer%E2%80%99s-disease-2015-update (58 PDF pages)

Introduction

Vision Statement

National Alzheimer’s Project Act

Alzheimer’s Disease and Related Dementias

The Challenges

Framework and Guiding Principles

Goals as Building Blocks for Transformation

2015 Update

 

The Connection between Down Syndrome and Alzheimer’s Disease

Many, but not all, people with Down syndrome develop Alzheimer’s disease when they get older. Alzheimer’s is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks.

Alzheimer’s disease is the most common cause of dementia among older adults. Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—and behavioral abilities to such an extent that it interferes with a person’s daily life and activities.

People with Down syndrome are born with an extra copy of chromosome 21, which carries the APP gene. This gene produces a specific protein called amyloid precursor protein (APP). Too much APP protein leads to a buildup of protein clumps called beta-amyloid plaques in the brain. By age 40, almost all people with Down syndrome have these plaques, along with other protein deposits, called tau tangles, which cause problems with how brain cells function and increase the risk of developing Alzheimer’s dementia.

However, not all people with these brain plaques will develop the symptoms of Alzheimer’s. Estimates suggest that 50 percent or more of people with Down syndrome will develop dementia due to Alzheimer’s disease as they age into their 70s.

Alzheimer’s Disease Symptoms

Many people with Down syndrome begin to show symptoms of Alzheimer’s disease in their 50s or 60s. But, like in all people with Alzheimer’s, changes in the brain that lead to these symptoms are thought to begin at least 10 years earlier. These brain changes include the buildup of plaques and tangles, the loss of connections between nerve cells, the death of nerve cells, and the shrinking of brain tissue (called atrophy).

The risk for Alzheimer’s disease increases with age, so it’s important to watch for certain changes in behavior, such as:

  • increased confusion
  • short-term memory problems (for example, asking the same questions over and over)
  • reduction in or loss of ability to do everyday activities

Other possible symptoms of Alzheimer’s dementia are:

  • seizures that begin in adulthood
  • problems with coordination and walking
  • reduced ability to pay attention
  • behavior and personality changes, such as wandering and being less social
  • decreased fine motor control
  • difficulty finding one’s way around familiar areas

Currently, Alzheimer’s disease has no cure, and no medications have been approved to treat Alzheimer’s in people with Down syndrome.

Down Syndrome and Alzheimer’s Disease Research

Alzheimer’s can last several years, and symptoms usually get worse over time.  Scientists are working hard to understand why some people with Down syndrome develop dementia while others do not. They want to know how Alzheimer’s disease begins and progresses, so they can develop drugs or other treatments that can stop, delay, or even prevent the disease process.

Research in this area includes:

  • Basic studies to improve our understanding of the genetic and biological causes of brain abnormalities that lead to Alzheimer’s
  • Observational research to measure cognitive changes in people over time
  • Studies of biomarkers (biological signs of disease), brain scans, and other tests that may help diagnose Alzheimer’s—even before symptoms appear—and show brain changes as people with Down syndrome age
  • Clinical trials to test treatments for dementia in adults with Down syndrome. Clinical trials are best the way to find out if a treatment is safe and effective in people.

 

Alzheimers Disease Neuroimaging Initiative (ADNI)

A public-private partnership, the purpose of ADNI is to develop a multisite, longitudinal, prospective, naturalistic study of normal cognitive aging, mild cognitive impairment (MCI), and early Alzheimer’s disease as a public domain research resource to facilitate the scientific evaluation of neuroimaging and other biomarkers for the onset and progression of MCI and Alzheimer’s disease.

Dr. Laurie Ryan of the NIA gives a brief overview of ADNI in this video:

https://youtu.be/0rBVe0Fwnik

Dr. Thomas Obisesan of Howard University, an ADNI study participant, and a study companion describe ADNI and what it’s like to be involved in the study

https://youtu.be/rK1yWvvHHl8

Learn more about this topic at https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-people-down-syndrome.

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1:00PM 11/13/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

REAL TIME Coverage of this Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

1:00 p.m. Panel Discussion Genomics in Prenatal and Childhood Disorders

Genomics in Prenatal and Childhood Disorders

     Moderator:

David Sweetser, M.D., Ph.D.
Unit Chief, Division of Medical Genetics; Attending Physician in Pediatric Hematology/Oncology,
Massachusetts General Hospital for Children

Genomics revolutionized medicine and genetic variation in a larger scale

Cases one on Causing Autism – mutations in a gene of synapse formation, clinical trials

Treatment: IGF1

Genetics: embryo – implant only the healthy embryo – newborn comprehensive genetics testing in the medical record integrated – Standard language of GENE-DRUG interaction not only drug-drug interaction

Potential Harms: May or may not happen disease – stigma issues

Explaining to parents the conditions is very difficult for MDs

Panelists:

3. Diana Bianchi, M.D.
Executive Director, Mother Infant Research Institute;
Vice Chair for Research and Academic Affairs,
Department of Pediatrics; Attending Geneticists and Neonatologist;
Natalie V. Zucker Professor, Tufts University School of Medicine

Medical Geneticist – Pediatrics

  • Prenatal screening and diagnosis – chromosomal abnormality – Down Syndrome, testing is more precise 70% fewer procedures to correct defects due to screening prenatally.
  • Prenatal diagnostics — patient is not in front of us, ultrasound examination, options to terminate pregnancies, genetic counseling — changed due to Genomics
  • Prenatal treatment to down syndrome before the birth – Transcriptomic approach, treat the fetus prebirth
  • Standard of care – all pregnant women – must receive from MD the option for screening for down syndrome, it is a test positive or negative
  • NOW – DNA allows to test for  fetal sex, chromosome in maternal circulation fetal and maternal genetics — Mother may have chromosomal variation
  • high false positive – DNA for Down Syndrome, 97% effective Micro duplication only 5%
  • genetics information protection act – sue prospective employer using Genome, life insurance issues
  • most data available is on Down Syndrome, of all parents informed of a fetus with Down Syndrome – 40% continues the pregnancy
  • accuracy in testing, offering choice and treatment are LEADING principles NOT elimination of a disease (i.e. down syndromes)
  • in ten years — GENOME OF EVERY FETUS TO BE SEQUENCE

for reference see Prenatal Treatment of Down’s Syndrome: a Reality?

and ref list by Dr. Bianchi

2. Holmes Morton, M.D. @ClinicSpecChild
Medical Director, Clinic for Special Children

Small population in Lancaster, PA – risk for untreatable disease 52,000 screens 4.2 millions in US are screened Target mutation analysis, diagnosis very effectively. Harrisburg, PA – small scale natural history studies

Carrier testing offered in 70s. Discourages  from marriage, culture reaction is different. Working in the community, clinical practice using exon sequencing, combine population genetics and molecular biology.Translate Genomics to Clinical, small number of risk factors

History of genetics in population important to establish treatment

Upon birth, affected newborns get matching bone marrow transplant, thus, bypass stem cells – Gene therapy is another thing

1. Benjamin Solomon, Ph.D., M.D.
Chief, Division of Medical Genomics,
Inova Translational Medicine Institute

Longer term, statistical model in asthma research,  rigorous process on patient consent, life insurance, mutation that parents also have. Consequences: actionable findings are communicated
135 Genes – sequencing for some conditions
100,000 deliveries 10% ENTER THE STUDY, CASE BY CASE BASIS O PARTICIPATE, WHO SHOULD BE TESTED

Questions from the Podium

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

@HarvardPMConf

#PMConf

@SachsAssociates

@MGH

@MassGeneral

@TuftsMedicalCtr

@MedscapePeds

@ClinicSpecChild

@InovaHealth

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Tufts Health Plan to Cover Sequenom’s MaterniT21, Pathwork’s Tissue of Origin Tests

Reporter: Aviva Lev-Ari, PhD, RN

http://www.genomeweb.com/mdx/tufts-health-plan-cover-sequenoms-maternit21-pathworks-tissue-origin-tests

NEW YORK (GenomeWeb News) – Tufts Health Plan will begin covering Sequenom’s MaterniT21 Plus trisomy 21 test and Pathwork Diagnostics‘ Tissue of Origin test starting Oct. 1.

In an update to providers posted on its website, the health plan said that it may authorize coverage of the MaterniT21 test for patients who are plan members if they are at least 35 years old when they give birth; have a fetal aneuploidy screening test result including maternal serum screening and/or ultrasound evaluation that indicates the possibility of trisomy 21; or the plan member has a family history or prior pregnancy involving aneuploidy.

In a research note Oppenheimer analyst David Ferreiro said that Tufts Health Plan has approximately 1 million lives under coverage and a network of 90 hospitals and 25,000 healthcare providers.

“We view this decision as an incremental positive for [Sequenom] and as validation of the value proposition MaterniT21 presents to payors,” he said. “The adoption rate is encouraging and could positively impact payor decisions, further entrenching,” the company.

Two weeks ago, Sequenom said that in the second quarter revenues from its Sequenom Center for Molecular Medicine diagnostic services rose five-fold to $8.1 million driven by the MaterniT21 Plus test, which was launched in the fall. The test also detects for T18 and T13.

As adoption of the test continues to ramp at an increasing rate, the San Diego-based company increased its internal goal of billed MaterniT21 Plus tests for 2012 to 50,000 from an earlier goal of 40,000.

The company has stopped announcing coverage decisions by individual plans following an incident in the spring in which Coventry Health Care National Networkterminated a coverage decision for MaterniT21 Plus one week after Sequenom said that Coventy would cover the test. Sequenom said at the time that Coventry’s decision was without cause and was not a judgment on the company, Sequenom CMM, or its products.

In a statement today to GenomeWeb Daily News, a Sequenom spokesperson declined to disclose the terms of the contract with Tufts Health Plan. She said that Sequenom CMM has more than 26 million live under contract, and “we operate as an out-of-network laboratory where we are not yet contracted and bill payors accordingly.”

Tufts Health Plan also said that it will begin coverage of Pathwork Diagnostics’ Pathwork Tissue of Origin test, beginning on Oct. 1. The test is for the identification of challenging tumors, including poorly differentiated, undifferentiated, and metastatic cancers.

The plan said it may authorize coverage of the test if it is ordered by an oncologist and the plan member is diagnosed with metastatic cancer; the clinical evaluation has not identified the primary site of the cancer; the pathology report is submitted to Tufts Health Plan for review; and the pathology examination is unable to conclusively identify the primary site, or has identified two or more possible primary sites.

Use of the test to confirm a diagnosis will not be covered by the health plan.

 

 

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