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Roskamp Institute Articles Better Science. Real Discovery.

February 14, 2012

News:KEY CLINICAL TRIAL OF ALZHEIMER’S DISEASE DRUG BEGINS IN EUROPE DRUG DISCOVERED BY ROSKAMP INSTITUTE RESEARCH

Filed under: Uncategorized — Tags: , , , — Gogce Crynen @ 12:46 pm
Contact: Steve Klindt
Tel: Tel:941-752-2949 x 390
Email: Sklindt@roskampinstitute.net

KEY CLINICAL TRIAL OF ALZHEIMER’S DISEASE DRUG BEGINS IN EUROPE DRUG DISCOVERED BY ROSKAMP INSTITUTE RESEARCH
SARASOTA, FL (Feb. 14) –

A research team today announced the launch of a European large-scale clinical trial of Nilvadipine, an Alzheimer’s disease drug developed at the Roskamp Institute (www.rfdn.org) in Sarasota. More than 500 Alzheimer’s patients in nine European countries will participate in the phase III trial designed to study the effectiveness of the medication.

“We believe that Nilvadipine blocks the production of amyloid proteins linked to Alzheimer’s disease,” said Roskamp Institute President and CEO Michael Mullan, M.D., Ph.D., who along with Associate Director Fiona Crawford, Ph.D., and Daniel Paris Ph.D. led the team that developed the drug. “That means Nilvadipine is aimed at addressing the actual disease, and not just the symptoms.”

A consortium of medical teams from nine European countries is meeting in Ireland this week to plan the US$10 million multicenter study. Phase III studies are usually the last step in the regulatory process before a drug can move into clinical practice. The consortium, called NILVAD for Nilvadipine/Alzheimer’s Disease, will involve participants from Ireland, England, Hungary, Greece, France, Sweden, Germany, Italy and the Netherlands.

The 500 participants, who have mild to moderate cognitive impairments, will begin the double-blind study this fall. Each participant will be followed for 18 months to see if the drug produces a change in cognitive abilities.

“We won’t cure Alzheimer’ disease without clinical trials,” said Crawford, who added that major pharmaceutical companies have not been able to come up with an effective drug. “Currently, there are only eight interventions underway in phase III trial, and it’s a tremendous achievement for a small research institute like ours to be part of the process.”

April 15, 2011

VA Research Day, at James A. Haley Veterans’ Hospital, on April 14th 2011

Filed under: Uncategorized — Tags: , , , — Gogce Crynen @ 9:55 am

Roskamp Institute scientist and Open University PhD students presented posters during VA Research Day, at James A. Haley Veterans’ Hospital, on April 14th 2011. You can find the abstracts of these poster below.

Proteomic-based identification of a CNS biological profile of delayed cognitive impairment in mice exposed to Gulf War agents.

Laila Abdullah,* Alex Bishop,* John Phillips, Scott Ferguson,*†‡ Benoit Mouzon,*†‡*‡ Jon Reed,*† Gogce Crynen,*‡ Myles Mullan,*† Venkat Mathura,* Michael Mullan,*†

Ghania Ait-Ghezala,*†‡ and Fiona Crawford*†‡

*Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243

†James A. Haley VA Hospital, 13000 Bruce B. Downs Blvd, Tampa, FL, 33612

‡The Open University, Walton Hall, Milton Keynes, MK7 6AA

Background: Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment currently available.  It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI.  Aim: In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER.  Method: Wild-type CD1 mice were exposed to 2mg/kg PB and 200 mg/kg of PER via i.p. in DMSO daily for 10 days and the control group received DMSO only.  Following exposure, neurobehavioral profile were examined using the Rotarod test to assess motor deficits, the Open Field test for anxiety-related changes and the Morris Water Maze test to assess spatial memory.  Mice were subsequently euthanized for proteomic and histopathological studies.  Results: Mice exposed to PB and PER over 10 days showed an increase in anxiety-like behavior and delayed cognitive impairment compared to control mice that received vehicle only.  Hence, GW agent exposed mice recapitulate the chronic and delayed emergence of the cognitive impairment associated with GWI.  Comparative proteomic approaches showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent exposed mice compared to controls.  Proteins associated with the endocrine and the immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI.  The presence of astrogliosis in the GW agent exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI.  Conclusion: These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness.  Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways to target for development of novel therapeutics for the treatment of GWI.

Funding:

This work is supported by a Congressionally Directed Medical Research Program award to Dr. Fiona Crawford (Grant#: GW080094).

Behavioral outcome in a mouse model of single and multiple concussions

Benoit Mouzon*†, Helena Chaytow*, Corbin Bachmeier*, Michael Mullan*†, and Fiona Crawford*†
*Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243

†James A. Haley VA Hospital, 13000 Bruce B. Downs Blvd, Tampa, FL, 33612

Abstract:

Concussion or mild traumatic brain injury(mTBI), is the most common type of TBI. The World Health Organization (WHO) estimated that between 70 and 90% of head injuries that receive treatment are mild. Despite its prevalence, mTBI has only recently become accepted as a major health issue since the intense media attention brought to the public on the high incidence of TBI in military conflicts and on high-profile professional athletes. In the United States, every year, more than 2 million people sustain a TBI, principally as a result of falls (35.2%), motor vehicle accidents (17.3%), violence, sports-related injuries and nearby explosions on the battlefield.  An understanding of the cellular mechanisms succeeding TBI is important as this is a major public health problem in industrialized countries.

The purpose of this study is to develop and characterize a novel mTBI model in rodents that replicates the pathological components or phases of human clinical mTBI. This model has several advantages over currently available rodent models of TBI like controlled cortical impact, weight drop, or the fluid percussion model. One advantage of this model is that the location of the hit on the midline allows the whole brain to be used for analyses.  This new model is also of particular interest to investigate military or sports related concussions, where the soldier/athletes usually receive multiple hits over a relatively short period of their lifetime. Repetitive mTBI is believed to be associated with at least two devastating complications.  An increase in brain vulnerability to a second concussive impact and/or 2) chronic cognitive impairments, such as chronic traumatic encephalopathy (CTE), which are often associated with accelerated neurodegeneration in specific brain regions.  These  data validate our model of mild head injury and demonstrate a temporal window of vulnerability to repetitive head trauma that results in behavioral dysfunction.

APP is Internalized After CD40 Ligation Which Increases Aβ Production

Ghania Ait-Ghezala1,2, Ekta Shah1, Jeremy Frieling1, Helena Chaytow1, Claude-Henry Volmar3,and Michael J. Mullan1,2

1Roskamp Institute, Sarasota, FL 34243.  2James A. Haley Veterans’ Hospital, Tampa, FL 33612.  3Scripps Research Institute, Jupiter, FL 33458.

ABSTRACT

CD40, a member of the tumor necrosis factor receptor superfamily, and its cognate ligand CD40L both have elevated levels in the brains of Alzheimer’s disease (AD) patients compared to controls. We have shown that pharmacological or genetic interruption of CD40/CD40L interaction results in mitigation of AD-like pathology in vivo in transgenic AD mouse models, and in vitro. Previously we showed that CD40L stimulation induces Ab production potentially through the g-secretase. Particularly we report an increase in levels of Ab (1-40) and Ab (1-42). We have also recently shown that CD40 ligation triggers internalization of APP, and that internalization by endocytosis is associated with increased Ab production. To further test whether lipid raft translocation of APP is indeed triggered by CD40 ligation, we have expressed a CD40/CD45 chimera in vitro. We will ultimately use this chimera to measure the impact of ligation on Ab production.

CD40 Ligand Deficiency Improves Rate of Functional Recovery Following Traumatic Brain Injury

Scott Ferguson1,2, Benoit Mouzon1,2, John Phillips1, Gogce Kayihan1,2, Helena Chaytow1, Alex Bishop1, Laila Abdullah1, Myles Mullan1, Venkatarajan Mathura1,2, Michael Mullan1,2, Fiona Crawford1,2

1Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243

2James A. Haley VA Hospital, 13000 Bruce B. Downs Blvd, Tampa, FL, 33612

Abstract

Traumatic brain injury (TBI) has been diagnosed in 178,876 service members from 2000 to the first quarter of 2010. The neurobehavioral sequelae of TBI persist long after the injury, which consists of both a primary insult to the brain as well as secondary injury that occurs in the hours and days immediately thereafter.  In order to find targets for therapeutic intervention we have analyzed the proteomic profile of the response to injury by Apolipoprotein E (APOE) transgenic mice.  Polymorphisms in APOE are known to impact the outcome after TBI, with the APOE4 allele (and concomitant ApoE4 expressed protein) associated with worse outcome than ApoE3 following TBI.

Proteomic analysis of the response to injury by APOE transgenic mice revealed multiple pathways differentially regulated in APOE3 and APOE4 mice following injury, suggesting a potential role of those pathways in modulating the outcome from injury.  One of these pathways involved CD40-related molecules.  CD40 and its ligand, CD154, have been shown to be upregulated in patients following cerebral ischemia (Garlichs et al, 2003). A study by Ishikawa et al (2005) also showed CD40 and CD40 ligand deficient mice have reduced infarct volume in a mouse model of ischemia, and given that ischemic conditions are known to occur in the brain following TBI, we used CD40 ligand (CD40L) knockout mice (Jackson Laboratories) to study the effect of CD40 signaling in a CCI model of severe TBI.

Rotarod testing was used to evaluate neuromotor skills and the Barnes maze was employed to test spatial learning and memory.  Our results showed that CD40L knockout mice showed an improved rate of functional recovery following TBI compared to wild type controls, as well as improved performance on both the Rotarod and Barnes maze tasks overall.

September 13, 2010

News:Scientific team at the Roskamp Institute found evidence to support that processes controlling the growth of cerebral blood vessels are altered in the brains of transgenic mouse models of Alzheimer’s disease

Sarasota, Florida). Scientists at the Roskamp Institute in Sarasota, in collaboration with researchers from the H. Lee Moffitt Cancer Center in Tampa, have found laboratory evidence that the processes controlling the growth of cerebral blood vessels are altered  in the brains of transgenic mouse models of Alzheimer’s disease (AD). Scientists say the discovery will provide a better understanding of the role of cerebrovascular lesions in AD brains and may explain why vascular insults synergistically precipitate the cognitive presentation of AD. In addition, their research may provide new therapeutical approaches which are desperately needed to tackle this devastating disorder. AD is the most common form of dementia among the aging population and is characterized by the intracerebral accumulation of a small protein called b-amyloid, as well as, neurofibrillary tangles that form in the neurons of the affected patients. In addition to neuronal damages, AD brains also present evidence of capillary degeneration and a reduction in brain capillary density which probably contribute to the decreased cerebral blood flow reported in all patients suffering from the disease. The growth of blood vessels (or angiogenesis) is controlled by the balance between several growth factors that can stimulate their growth and other molecules that inhibit their formation. The amount of growth factors that normally stimulate angiogenesis is elevated in AD brains, which could suggest that the growth of cerebrovessels would be stimulated in AD. The growth of tumors is dictated by their vascularization, this is particularly true for brain tumors which are highly vascularized. Therefore, in order to determine whether angiogenesis was possibly altered in AD brains, the researchers implanted brain tumors in transgenic mouse models of AD (that have been genetically engineered to reproduce some of the AD brain pathology) as well as normal mice and measured the growth of the tumors in the animals. “Interestingly, we observed that the growth and vascularization of brain tumors was reduced in transgenic mouse models of AD compared to normal mice, suggesting that the AD brain does not constitute a favorable environment to support the growth of new blood vessels.” said Dr. Daniel Paris of the Roskamp Institute, lead author of the study published in the Journal of Neuroscience (J. Neurosci. 2010;30(34):11251-8). “Our data suggest the growth of new brain capillaries that takes place following a stroke for example, and allows for a restoration of the cerebral blood flow in the damage area, will be inhibited in AD. This may explain why vascular insults such as stroke are known to accelerate the cognitive decline in AD patients. Overall, our work suggests that therapies stimulating brain vascularization may be beneficial in AD patients.”, Dr. Paris added. Epidemiological studies have highlighted that the incidence of cancer is reduced in AD patients whereas the prevalence of AD is reduced in patients with an history of cancer suggesting a biological link between cancer and AD. “As the growth of blood vessels is required for the development of tumors, our work suggesting some impairment in the growth of blood vessels in AD may provide a biological mechanism explaining this intriguing relationship between cancer and AD.”, Dr. Paris said. The Roskamp Institute is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete. For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.RoskampInstitute.com.

September 2, 2010

Event: Journal Club “Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer’s disease compared to cognitively intact control subjects”


Alex Bishop will be presenting the paper on Friday (9/3/2010) at Roskamp Institute.

Title:  “Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer’s disease compared to cognitively intact control subjects”

Biochimica et Biophysica Acta 1801 (2010) 951–959

Journal Club is held every Friday between 4 pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

August 6, 2010

Governor Charlie Crist visits Roskamp Institute

Filed under: news — Tags: , , , — Gogce Crynen @ 1:28 pm

Governor Charlie Crist visited our Institute on Thursday, and was briefed about the most recent scientific breakthroughs that have occurred at the Institute, followed by a full tour of the laboratories.  Impressed with what he saw, Gov. Crist referred to the Institute as “Florida’s best-kept scientific secret.”

Alzheimer’s disease is a growing epidemic in Florida, and the Governor and Senatorial candidate was receptive to concerns raised by Institute scientists regarding future funding opportunities for Alzheimer’s research. There is currently no State funding for Alzheimer’s research in Florida, despite this state being one of the hardest hit by this devastating disease.  When such funds once more become available it is hoped that they will be distributed using a peer-review process (as used for State funding of Cancer research) so that the tax payers receive most “bang for their buck” with the best research programs receiving the funding.

The visit underscores the growing prominence of the Roskamp Institute within the Sarasota/Manatee community and greater local recognition for the Institute’s nationally and internationally recognized contributions to research progress in Alzheimer’s Disease, Cancer and other disorders. Gov. Crist also discussed the Institute’s research programs that are of critical importance to the military and veterans populations – Traumatic Brain Injury, Post Traumatic Stress Disorder and Gulf War Illness.  He was also interested in the innovative Ph.D. program now flourishing at Roskamp, as well as the Institute’s for-profit spin off, Archer Pharmaceuticals.

Gov. Crist’s visit was the most recent in a series of high-profile visits to the Institute, which have included visits from Senator Bill Nelson and Congressman C. W. Bill Young.  James Humphrey, Roskamp COO was encouraged by the visit, as it was yet another means by which the the Institute can “reach out into the public domain” and raise awareness of the scope of research being conducted in the Sarasota/Manatee area

August 4, 2010

Roskamp Institute in the news

Filed under: news — Tags: — Gogce Crynen @ 10:22 am

Our chief operating officer James Humprey attended Manatee County Commissioners’ “We’re Listening” Session.

For details please visit Bradenton Times web site or Bradenton.com

July 12, 2010

Event: Journal Club “Identification of Caspase-6-Mediated Processing of the Valosin Containing Protein (p97) in Alzheimer’s Disease: A Novel Link to Dysfunction in Ubiquitin Proteasome System-Mediated Protein Degradation”

Chris Mayer will be presenting the paper on Friday (7/16/2010) at Roskamp Institute.

Title: Identification of Caspase-6-Mediated Processing of the Valosin Containing Protein (p97) in Alzheimer’s Disease: A Novel Link to Dysfunction in Ubiquitin Proteasome System-Mediated Protein Degradation

Journal: The Journal of Neuroscience,

April 28, 2010, 30(17):6132-6142

Journal Club is held every Friday between 4 pm-5pm. For change in schedule please check our twitter account or facebook page. Please join us!

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

July 9, 2010

News: South East High wins first place in national final at 32nd Annual Technology Student Association (TSA) Conference

Filed under: news — Tags: , , , — Gogce Crynen @ 1:37 pm

South East High School technology students from the school district won first place for scientific visualization of diabetes at the 32nd Annual Technology Student Association (TSA) Conference held June 28-July 2 in Baltimore, Maryland.

The South East High TSA students worked closely with the scientist from the Roskamp Institute on the project. The

Technology Student Association is the only student organization dedicated exclusively to students enrolled in technology education classes at the K-12 level. TSA is recognized by the U.S. Department of Education, many state agencies, the National Association of Secondary School Principals, the International Technology Association and the National Coalition of Career and Technical Student Organizations. The TSA National Conference draws more than 1,200 participants from as many as 30 states and several European nations annually.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

July 2, 2010

Roskamp Institute Gulf War Illness research program

Dr. Crawford presented the Roskamp Institute Gulf War Illness research program to the Research Advisory Committee on Gulf War veterans illnesses on June 28-29th at the Veterans Administration in Washington, DC. Her presentation included details of genomic and proteomic analyses of laboratory models of exposure to agents that have been implicated in GWI, which is targeted toward identification of plasma biomarkers and molecular targets for therapeutic intervention. Other speakers included Captain Melissa Kaime, M.D., Director of the Congressionally Directed Medical Research Program, Dr. William Goldberg, Scientific Program Manager for the VA Office of Research and Development, and Mr. John Gingrich, Chief of Staff at the Department of Veterans Affairs. The Committee is chaired by Mr. James Binns, a former Principal Deputy Assistant Secretary of Defense for International Security Policy, and a Vietnam veteran. Other committee members include Dr. Floyd Bloom, Professor Emeritus of the Scripps Research Institute, Dr. Kimberly Sullivan of Boston University School of Public Health and Scientific Coordinator for the Committee, and Mr. Anthony Hardie, Executive Assistant of the Wisconsin Department of Veterans Affairs, and a Gulf War and Somalia veteran.

June 21, 2010

Event: Journal Club “The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer’s disease”

Nowell (Jim) Ganey will be presenting the paper on Friday (6/25/2010) at Roskamp Institute.

Title:The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer’s disease.

Journal : Biomaterials.

2010 Jul;31(21):5608-18. Epub 2010 Apr 28.

Journal Club is held every Friday between 4 Pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949


June 18, 2010

News:Nomination for Business/Education Partnership Award through the School District of Manatee County’s ePIE program

The Roskamp Institute has been nominated for a Business/Education Partnership Award through the School District of Manatee County‘s ePIE program. Since 1990, this awards program recognizes businesses, organizations, and individuals who have made the commitment to work together to enhance education in the School District of Manatee County. The awards ceremony will be held in August.  Last year 2009  the Roskamp Institute won a Business/Education partnership award for its work with South East High School.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

June 17, 2010

News:Roskamp Institute was recognized by the South East High School Technical Student association for partnering will the in a diabetes project

Filed under: news — Tags: , , , , — Gogce Crynen @ 1:49 pm

On Tuesday June 15th the Roskamp Institute was recognized by the South East High School  Technical Student association for partnering will the in a diabetes project.  At the Victory celebration banquet held at South East High following the TSA teams success in the State TSA finals. The Diabetes project was awarded second place in the medical visualization category.  The project will be used in the National Finals which are being held in Baltimore on June 27th.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

June 14, 2010

Event: Journal Club “NF-jB activity affects learning in aversive tasks: Possible actions via modulation of the stress axis”

Scott Ferguson will be presenting the paper on Friday (6/18/2010) at Roskamp Institute.

Title:NF-κB activity affects learning in aversive tasks: Possible actions via modulation of the stress axis

Journal: Brain, Behavior, and Immunity

doi:10.1016/j.bbi.2010.04.005

Journal Club is held every Friday between 4 Pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

June 11, 2010

News

Filed under: news — Tags: , — Gogce Crynen @ 10:36 am

Bradenton Herald Business section published an article about on going collaboration between Roskamp Institute and Southeast High school students. You can reach it via this link.

June 8, 2010

Event Journal Club:Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice

Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice by Rhein et al.

Alex Bishop will be presenting the paper on Friday (6/11/2010) at Roskamp Institute.

Journal Club is held every Friday between 4 Pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

May 17, 2010

Do You Or Someone You Care For Suffer From Alzheimer’s Disease?

ALZHEIMER’S DISEASE

A research study is being conducted in our area to evaluate an investigational medication for Alzheimer’s disease.

Qualified participants may receive:

– Study related medical care

– Study medication

– Compensation for time and travel

Please call now for more info:    Dr. Andrew Keegan

941-256-8018 ext. 353

The Roskamp Institute Memory Clinic and Clinical Trials Division provide a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

May 11, 2010

NEWS RELEASE:Investigational Immune Intervention Slows Brain Atrophy in Alzheimer’s Patients


Media Contact:

Cheryl Rindfleisch, Roskamp Institute

941-256-8018 x356

crindfleisch@rfdn.org or

Jeffree Itrich  858-622-5827

jitrich@ucsd.edu

May 10, 2010

Investigational Immune Intervention Slows Brain Atrophy in Alzheimer’s Patients

  • 18-Month Phase 2 Study is First to Show Combined Benefits of IGIV on Clinical Outcomes and Brain-Imaging Measures
  • Phase 3 Study Now Enrolling Participants at the Roskamp Institute in Sarasota

An investigational treatment, Immune Globulin Intravenous (IGIV), which utilizes naturally occurring antibodies in human blood has preserved the thinking abilities of a small group of mild-to-moderate Alzheimer’s patients over 18 months and significantly reduced the rate of brain atrophy. The study was conducted at the New York Presbyterian Hospital/Weill Cornell Medical Center and the results were presented at the American Academy of Neurology (AAN) annual meeting in Toronto in mid-April.

An important next step Phase 3 study of IGIV, called The Gammaglobulin Alzheimer’s Partnership (GAP) Study, is now underway throughout North America. Locally the study is being conducted at the Roskamp Institute in Sarasota, Florida. The Phase 3 study is a prospective, 18-month, randomized, double-blind, placebo-controlled, two dose arm of parallel groups in 360 subjects of both genders, aged 50-89 years old with mild-to-moderate Alzheimer’s disease (AD).

“The cognitive and functional outcomes and neuroimaging results from this 18-month Phase 2 study clearly support continued evaluation for Alzheimer’s disease in a larger number of patients,” says Dr. Paul Aisen, director of the Alzheimer’s’ Disease Cooperative Study at UCSD, one of the study’s sponsors. “The important next step is to fully enroll and complete the ongoing Phase 3 study in hope of confirming the Phase 2 findings and fully understand the potential benefit in AD.”

The Phase 2 study used Gammagard Liquid and Gammagard S/D for Alzheimer’s produced by Baxter Healthcare. The same products are being used in the Phase 3 Gap Study.

“IGIV is being evaluated as a possible treatment for AD because of its known antibodies to beta-amyloid, thought to be the major element of amyloid plaques in the brains of people with AD,” says Dr. Andrew Keegan, the study’s principal investigator at the Roskamp Institute.  “IGIV is not approved for treating AD but is approved in the U.S. and other countries for treating immune deficiency and autoimmune disorders,” he added. “It has been around for a long time and has an excellent safety record.”

Dr. Norman Relkin, director of the Memory Disorders Program at New York Presbyterian Hospital/Weill Cornell Medical Center and principal investigator of the Phase 2 study reported at the AAN that patients who received IGIV once or twice a month for 18 months had significantly lower rates of ventricular enlargement (6.7% vs 12.7% per year) and less whole brain atrophy (1.6% vs 2.2% per year) than control subjects who initially received the placebo. Relkin’s findings were based on two independent analyses of brain-imaging data from 20 patients who underwent serial MRI scans during the Phase 2 study of IGIV for Alzheimer’s disease (AD).

The brain of a typical AD patient shrinks three to four times faster than a healthy equivalent older adult due to the accelerated brain cell death. Shrinkage of brain tissue causes the fluid-filled ventricles at the brain’s center to enlarge at a faster rate than normal. Changes in the size of the brain and ventricles can be measured accurately by analyzing results from two or more MRI scans at intervals of several months apart. The unprecedented reductions in these measures after IGIV was administered in the Phase 2 study may indicate that IGIV exerts a disease-modifying effect that the current generation of AD treatments do not. Relkin found that rates of brain shrinkage were independent of the subject’s age, gender and brain volume at the beginning of the study but strongly correlated with IGIV dose and the clinical outcomes after 18 months of intervention. The research team also found that patients who responded best to IGIV did not measurably decline over 18 months, plus had an average rate of brain shrinkage and average rate of ventricular enlargement comparable to the rate of normal elderly adults.

“A dose related effect of an Alzheimer’s intervention on brain ventricular enlargement has never been seen before, and it suggests that IGIV may be sparing brain tissue,” says Dr. James Brewer, a neurologist and assistant professor in the neurosciences department at UCSD.

Dr. Diamanto Tsakanikas, a neuropsychologist at Presbyterian Hospital/Weill Cornell Medical Center conducted cognitive testing of the Phase 2 study participants while blinded to whether the patients received IGIV or placebo. Her testing revealed that AD patients who received uninterrupted IGIV for 18 months showed significantly less decline in their overall function and thinking abilities than AD patients who were initially given the placebo.

The pivotal Phase 3 study now underway at the Roskamp Institute is funded by Baxter and National Institutes of Health (NIH) through the Alzheimer’s Disease Cooperative Study (ADCS).

The Phase 2 study was supported by Baxter Healthcare, the Citigroup Foundation and The Clinical Translational Science Center of Weill Cornell Medical College.

For further information on the Phase 3 study go to www.GAPSTUDY.com or http://www.alzheimers.org/clinicaltrials/fullrec.asp?PrimaryKey=282 .

Local Site:

Roskamp Institute

(941) 256-8018

www.rfdn.org

May 6, 2010

Anti-Tumoral Activity of a Short Decapeptide Fragment of the Alzheimer’s Abeta Peptide

By Daniel Paris • Nikunj Patel • Nowell J. Ganey • Vincent Laporte • Amita Quadros • Michael J. Mullan

Int J Pept Res Ther (2010) 16:23–3.  DOI 10.1007/s10989-010-9198-8

Abstract: The inhibition of angiogenesis is regarded as a promising avenue for cancer treatment. Although some antiangiogenic compounds are in the process of development and testing, these often prove ineffective in vivo, therefore the search for new inhibitors is critical. We have recently identified a ten amino acid fragment of the Alzheimer Ab peptide that is anti-angiogenic both in vitro and in vivo. In the present study, we investigated the antitumoral potential of this decapeptide using human MCF-7 breast carcinoma xenografts in nude mice. We observed that this decapeptide was able to suppress MCF-7 tumor growth more potently than the antiestrogen tamoxifen. Inhibition of tumor vascularization as determined by PECAM-1 immunostaining and decreased tumor cell  proliferation as determined by Ki67 immunostaining were observed following treatment with the Ab fragment. In vitro, this peptide had no direct impact on MCF-7 tumor cell proliferation and survival suggesting that the inhibition of tumor growth and tumor cell proliferation observed in vivo is related to the antiangiogenic activity of the peptide. Taken together these data suggest that this short Ab derivative peptide may constitute a new antitumoral agent.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

May 5, 2010

Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 levels in plasma in Alzheimer’s disease

Filed under: cd40 — Tags: , , , , , , — Gogce Crynen @ 9:36 am

By Ait-ghezala G, Abdullah L, Volmar CH, Paris D, Luis CA, Quadros A, Mouzon B, Mullan MA, Keegan AP, Parrish J, Crawford FC, Mathura VS, Mullan MJ.

Cytokine. 2008 Nov;44(2):283-7.

A continuous inflammatory state is associated with Alzheimer’s disease (AD) evidenced by an increase in proinflammatory cytokines around beta-amyloid (Abeta) deposits. In addition, functional loss of CD40L is shown to result in diminished Amyloid precursor proton (APP) processing and microglial activation, supporting a prominent role of CD40-CD40L in AD etiology. We therefore hypothesize that a peripheral increase in Abeta may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis. We measured plasma Abeta, sCD40 and sCD40L levels in 73 AD patients and compared to 102 controls matched on general demographics. We demonstrated that Abeta(1-40), levels of sCD40 and sCD40L are increased in AD and declining MMSE scores correlated with increasing sCD40L, which in turn, correlated positively with Abeta(1-42). We then combined sCD40, sCD40L, Abeta and APOE and found that this biomarker panel has high sensitivity and specificity (>90%) as a predictor of clinical AD diagnosis. Given the imminent availability of potentially disease modifying therapies for AD, a great need exists for peripheral diagnostic markers of AD. Thus, we present preliminary evidence for potential usefulness for combination of plasma sCD40, sCD40L along with Abeta(1-40) and APOE epsilon4 in improving the clinical diagnosis of AD.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

April 28, 2010

Roskamp Institute is participating in VA Research Week Activities

Filed under: Uncategorized — Tags: , , — Gogce Crynen @ 4:33 pm

Veterans Affairs is celebrating 85th year in research this week (April 26-30, 2010). One of the events is a poster session where scientists will be presenting their most recent work. We are proud to say that most of our PhD students and research assistants will be in the auditorium of the James A Haley VA Hospital in Tampa, FL to present their posters tomorrow (April 29th 2010). For more information about the VA Research Week please visit this site.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949


April 27, 2010

High serum Abeta and vascular risk factors in first-degree relatives of Alzheimer’s disease patients

By Abdullah L, Luis C, Paris D, Ait-ghezala G, Mouzon B, Allen E, Parrish J, Mullan MA, Ferguson S, Wood M, Crawford F, Mullan M. These findings were published in Molecular Medicine 2009 Mar-Apr;15(3-4):95-100.

Alzheimer’s disease is clinically characterized by progressive cognitive decline accompanied by the presence of amyloid plaques and neurofibrillary tangles in the brain of Alzheimer’s patients. A small protein fragment beta-amyloid (Abeta) with 42 amino acids is shown to deposit earlier in the disease process than the slightly shorter form (40 amino acid fragment).  Both species of this protein fragment are considered toxic to the brain and are shown to have an important role in causing Alzheimer’s disease.  Current research suggests that the disease process in Alzheimer’s begins long before the presence of palpable symptoms and widespread damage in the brain. Therefore, use of beta-amyloid seems promising in identification of individuals at-risk of developing Alzheimer’s disease.  Clinical studies have previously shown that blood and cerebrospinal fluid levels of Abeta may be helpful in diagnosis of Alzheimer’s disease but are influenced by factors such as presence of family history and other risk factors. The main objective of a recent study published by the scientists at the Roskamp Institute was to determine whether elevated blood Abeta levels among the first-degree relatives of patients with Alzheimer’s disease are associated with certain risk factors of cardiovascular disease that are also risk factors Alzheimer’s disease, such as hypertension.  Blood Abeta was measured in disease-free first-degree relatives of patients with Alzheimer-like dementia. Study participants were recruited as part of an ancillary study of the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT subpopulation) which was funded by the National Institutes of Health (UO1AG15477).  Examination of Abeta in this group of individuals showed that Abeta(1-40) fragment was positively associated with age and use of anti-hypertensive medications, but a negative relationship was observed in those individuals who experienced some increase in systolic blood pressure, despite being on anti-hypertensive medication.  On the other hand, the more toxic Abeta(1-42) was associated with statin use (medications used for lowering cholesterol) and with high-density lipoproteins was observed among statin nonusers. These findings suggest that high Abeta in blood samples of family history-enriched individuals may be due to enrichment of vascular risk factors and may reflect presymptomatic stage of Alzheimer’s disease.  As anti-hypertensive medications and statins are considered to be protective against Alzheimer’s disease onset, it remains to be determined whether their association with Abeta reflects mitigation of Abeta-related toxicity in the brain. Longitudinal evaluation of blood Abeta in this cohort will provide a better understanding of the significance of this association in Alzheimer’s disease etiology.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

April 26, 2010

Alzheimer’s Disease Anti-Inflammatory Prevention Trial

The Roskamp Institute Memory Center is actively following a large number of subjects who participated in the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT). Although earlier detection and the development of disease modifying treatment continues to be a primary focus of research and several potential compounds are under clinical trial, more prevention studies are needed.

The Roskamp Institute provides a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

April 23, 2010

Cross Validation of the Montreal Cognitive Assessment in Community Dwelling Older Adults Residing in the Southeastern US

By Cheryl A. Luis, Andrew Keegan, and Michael Mullan

Int J Geriatr Psychiatry. 2009 Feb;24(2):197-201.

Suitable methods of earlier detection of memory changes, before the full onset of a dementia are needed.  Methods such as imaging for abnormal protein accumulation in the brain and lumbar puncture to measure abnormal proteins in cerebral spinal fluid are not likely to be useful for wide-scale use due to costs and the invasive nature of the procedure.  In this study, we examined the utility of a brief cognitive screen (the Montreal Cognitive Assessment; MoCA), compared to a widely used instrument (the Mini-Mental State Exam; MMSE) in detecting older adults living in the community experiencing significant memory decline and the early signs of dementia. One hundred and eighteen individuals, over the age of 70, participated in the project. The MoCA proved to be highly sensitive in identifying participants with memory problems.  The MMSE was ineffective in comparison. Brief screening instruments such as the MoCA provide an objective and cost-effective means of determining the need for further evaluation of memory changes in older adults at risk for dementia.

The Roskamp Institute provides a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

April 22, 2010

Volunteers for early detection of cognitive decline in older adults

Dr. Cheryl Luis of the Roskamp Institute was awarded a New Investigator Research Grant from the Alzheimer’s Association in 2009.  She is studying the potential usefulness of a blood test in combination with a paper and pencil memory test for early detection of cognitive decline in older adults.  Additional research volunteers are needed.  If you or your loved one has been diagnosed with Alzheimer’s disease or Mild Cognitive Impairment and are interested in participating in a brief study, please call (941) 256-8018

The Roskamp Institute provides a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

April 20, 2010

Roskamp Institute hosted a town hall meeting for the Alzheimer’s Association.

Filed under: news — Tags: , , — admin @ 1:05 pm

Sarasota, FL The Roskamp Institute hosted a town hall meeting for the Alzheimer’s Association. Presented was “A Reason to Hope”, an Alzheimer’s Services and Treatment Update. The meeting was well attended by caregivers and local community leaders. Dr. Cheryl Luis, Associate Clinical Director of the Roskamp Institute Memory Center, presented some of her current research to the attendees. Dr. Maria Carrillo, Director of Medical and Scientific Relations, from the National Alzheimer’s Association home office in Chicago, updated the audience about the latest developments in the fight against Alzheimer’s disease. While Gloria Smith, President & CEO of the Alzheimer’s Association – Florida Gulf Coast Chapter, presented the various services and the resources available to victims of the disease and their caregivers. The audience took part in a very encouraging question and answer session with Dr. Carrillo.

After the town hall meeting, Dr. Carrillo toured the Institute’s laboratories and had lunch with the Institutes scientific and clinical staff where they discussed current scientific research and developments in the Alzheimer’s field.

Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.
For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.RoskampInstitute.com.

August 11, 2009

NSAIDS and their effect on Alzheimers disease

Filed under: Uncategorized — Tags: , , — admin @ 12:45 pm

Non-steroidal anti-inflammatory (NSAIDS) drugs such as Naproxen and Celecoxib do not improve cognition in at-risk older adults. These findings from the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT) were published this month in Archives of Neurology.  The Roskamp Institute Memory Clinic in Tampa was one of a handful of centers across the United States that took part in this primary prevention trial funded by the National Institute of Aging. The Tampa site enrolled over 400 subjects, age 70 or older with a reported family history of Alzheimer’s-like dementia.  During the 5-year study period, participants underwent annual cognitive testing and were randomly assigned to one of two treatments (Naproxen 220 mg twice daily, Celecoxib 220 mg twice daily) or a placebo. Although treatment was suspended in 2004, following a report of increased cardiovascular risk in another prevention trial, subjects continued annual follow-up.  Results examining the cognitive data collected up to 6 months after treatment was discontinued suggest that Naproxen may in fact have a small deleterious effect on cognition. However further study is needed to determine if this effect is mitigated or exaggerated over time, or if results were influenced by subjects who may have been in the early stage of a dementia. Drs. Cheryl Luis and Timothy Crowell, specialists in Neuropsychology, supervised the day-to-day aspects of the study in Tampa. Dr. Michael Mullan, director of the Roskamp Institute and principal investigator for the Tampa site served on the writing committee of the manuscript. Go to http://www.ncbi.nlm.nih.gov/pubmed/18474729 for more information.

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