A research team led by Mount Sinai School of Medicine has identified the mechanism behind a single gene linked to the causes of both Alzheimer's disease and Type 2 diabetes. The data show that a gene for a protein called SorCS1, which can cause Type 2 diabetes, impacts the accumulation of amyloid-beta (Abeta) in the brain. Abeta plays a key role in the development of Alzheimer's disease. The study is published in the Journal of Neuroscience.
Sam Gandy, MD, PhD, the Mount Sinai Professor in Alzheimer's Disease Research, Professor of Neurology and Psychiatry, and Associate Director of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine, led the study, together with first author Rachel Lane, PhD, a postdoctoral researcher in Gandy's Lab. Lane and Gandy analyzed both the brains of mice genetically engineered to be deficient in SorCS1 as well as cells engineered to express high levels of SorCS1. They found an increased level of Abeta in SorCS1-deficient mice, and low levels of Abeta in the cells overexpressing SorCS1.
"We knew that Type 2 diabetes could increase the risk for Alzheimer's disease, but we were not sure how that risk was caused or whether that diabetes risk would impact Abeta levels in the brain," said Dr. Gandy. "These results elucidate a common mechanism between diabetes and Alzheimer's and will bring us a step closer to identifying effective treatments for both diseases."
The researchers were also interested to find that the SorCS1-deficient mice had decreased levels of the protein Vps35, which was linked to Alzheimer's by Scott Small, MD, Associate Professor of Neurology, Columbia University College of Physicians and Surgeons, who co-authored the new study with Gandy. They propose that depleted SorCS1 may cause Vps35 levels to also decrease, leading to further accumulation of Abeta in mice. Further studies are required to better understand the impact of SorCS1 on Vps35 levels.
SorCS1 deficiency has been linked to Type 2 diabetes by geneticist Alan Attie, PhD, Professor of Biochemistry, University of Wisconsin, who also co-authored the new study. Rudolph E. Tanzi, PhD, Joseph P. and Rose F. Kennedy Professor of Neurology and Director of Genetics and Aging Research Unit at Harvard Medical School also contributed genetic data to the new study. Now that Dr. Gandy and his team have connected the same protein to increased Abeta levels, they can evaluate this protein and the family of proteins of which it is a member as drug targets for the treatment of both diseases.
"Alzheimer's and Type 2 diabetes are reaching epidemic levels, afflicting millions of Americans," said Dr. Gandy. "Their risk factors overlap and include high cholesterol, obesity, vascular disease, and inflammation. Now that we have a better understanding of where the connection between these two diseases originates on a molecular level, the next step is to develop drugs that will help reduce their devastating impact. Such drugs will require much more research, but having this new target helps put us on the right track."
The study was supported by the Cure Alzheimer's Fund, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases.
Source:
Mount Sinai Press Office
The Mount Sinai Hospital / Mount Sinai School of Medicine
пятница, 27 мая 2011 г.
четверг, 26 мая 2011 г.
ExonHit Therapeutics Awarded Two Discovery Grants By The US Federal Government
ExonHit Therapeutics (Paris:ALEHT)(Alternext: ALEHT) announced that the Company was awarded two grants to support two of its Research & Development projects under the Qualifying Therapeutic Discovery Project Program: AclarusDx™ in Alzheimer's disease and the EHT 107 program in oncology.
"We are excited to benefit from these grants as they are a recognition of the potential medical benefit of AclarusDx™ and the EHT 107 program," said Matthew Pando, PhD, Executive Vice President, Therapeutics of ExonHit Therapeutics. "These awards also further highlight the ability of our Genome-Wide SpliceArray™ discovery platform to generate both innovative diagnostic and therapeutic products. These grants will contribute to support the ongoing development of two programs targeting areas of high medical need."
These two grants totaling USD 0.3 million were awarded to ExonHit by the U.S. Secretary of Health and Human Services to support its Alzheimer's disease and oncology research and development projects. Among the determining criteria used by the Secretary in allocating funds were those projects that show potential to result in new therapies to treat areas of unmet medical need.
About the Qualifying Therapeutic Discovery Project Program
The Qualifying Therapeutic Discovery Project Program (QTDP) was created by the U.S. Congress as part of the recent health legislation reform (Patient Protection and Affordable Care Act of 2010) and is designed to foster biotechnology growth and innovation. The program also seeks to create and sustain biotechnology jobs in the US. QTDP grants are awarded to companies with fewer than 250 employees for projects related to the treatment or prevention of diseases through the conduct of preclinical or clinical studies.
The project recipients, jointly selected by the Treasury Department and the Department of Health and Human Services (HHS), were required to demonstrate preclinical or clinical research costs incurred in 2009 or 2010 expended on projects fulfilling specific criteria. More precisely, the grant targets therapeutic discovery projects that show a reasonable potential to:
- Result in new therapies to treat areas of unmet medical need or prevent, detect or treat chronic or acute diseases and conditions,
- Reduce the long-term growth of health care costs in the United States, or
- Significantly advance the goal of curing cancer within 30 years.
Source:
ExonHit Therapeutics
"We are excited to benefit from these grants as they are a recognition of the potential medical benefit of AclarusDx™ and the EHT 107 program," said Matthew Pando, PhD, Executive Vice President, Therapeutics of ExonHit Therapeutics. "These awards also further highlight the ability of our Genome-Wide SpliceArray™ discovery platform to generate both innovative diagnostic and therapeutic products. These grants will contribute to support the ongoing development of two programs targeting areas of high medical need."
These two grants totaling USD 0.3 million were awarded to ExonHit by the U.S. Secretary of Health and Human Services to support its Alzheimer's disease and oncology research and development projects. Among the determining criteria used by the Secretary in allocating funds were those projects that show potential to result in new therapies to treat areas of unmet medical need.
About the Qualifying Therapeutic Discovery Project Program
The Qualifying Therapeutic Discovery Project Program (QTDP) was created by the U.S. Congress as part of the recent health legislation reform (Patient Protection and Affordable Care Act of 2010) and is designed to foster biotechnology growth and innovation. The program also seeks to create and sustain biotechnology jobs in the US. QTDP grants are awarded to companies with fewer than 250 employees for projects related to the treatment or prevention of diseases through the conduct of preclinical or clinical studies.
The project recipients, jointly selected by the Treasury Department and the Department of Health and Human Services (HHS), were required to demonstrate preclinical or clinical research costs incurred in 2009 or 2010 expended on projects fulfilling specific criteria. More precisely, the grant targets therapeutic discovery projects that show a reasonable potential to:
- Result in new therapies to treat areas of unmet medical need or prevent, detect or treat chronic or acute diseases and conditions,
- Reduce the long-term growth of health care costs in the United States, or
- Significantly advance the goal of curing cancer within 30 years.
Source:
ExonHit Therapeutics
среда, 25 мая 2011 г.
Simultaneous Study Of Multiple Variables Allowed With Microgrid
Scientists at the U.S. Department of Energy's Brookhaven National Laboratory have developed a method for correlating the results of microscopic imaging techniques in a way that could lead to improved understanding, diagnosis, and possibly treatment of a variety of disease conditions, including Alzheimer's disease. The Laboratory has filed a U.S. provisional patent application for the invention.
The invention is essentially a micron-scale metallic marking grid upon which scientists place their samples -- biological tissues or inorganic samples such as minerals -- prior to imaging with different methods. "When the findings are analyzed, the grid can be used to 'map,' or orient, the images to one another, allowing us to study multiple variables in a single sample and better understand how they relate to one another," said biophysicist Lisa Miller, leader of the team that developed the new method.
For example, many diseases such as Alzheimer's are characterized by changes in both organic materials, such as proteins, as well as changes in the composition or concentration of inorganic trace metals (e.g., iron, copper, and zinc). Scientists have techniques -- infrared spectroscopy and x-ray fluorescence -- for studying each of these independently. But without a way to correlate the findings from the two methods, important information about the relationship between the organic and inorganic components can be missed.
"The x-ray and infrared-sensitive grid allows for the study of both pathological symptoms by precisely overlapping the results of these imaging methods," Miller said. "This ability to correlate images will ultimately lead to a more complete picture of many disease states."
The grid is deposited in two thicknesses onto an x-ray transparent material like mylar. It can be made of any metal, but gold is preferred. The "bars" of the grid are only a couple of nanometers thick, whereas the remainder of the metal surface is thicker. The dual thicknesses make the pattern sensitive to both infrared reflectivity and x-ray fluorescence imaging.
In another version of the invention, a single-layered grid is used to correlate light microscopy with x-ray fluorescence imaging.
Once the images are collected, custom software uses the grid patterns to align the images and correlate them with each other.
In addition to helping scientists study disease processes, the method could also be applied in monitoring and/or cleaning up environmental contamination, which is also characterized by the interplay of organic and inorganic factors.
This work was performed at Brookhaven Lab's National Synchrotron Light Source (NSLS), a source of intense infrared, ultraviolet, and x-ray beams used for studying atomic level details of a wide range of materials from biological molecules to semiconductor devices. Click here for more information on this study.
This project was funded by the National Institutes of Health with operational support for the NSLS provided by the Office of Basic Energy Sciences within the U.S. Department of Energy's Office of Science.
One of ten national laboratories overseen and funded primarily by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
Source: Karen McNulty Walsh
DOE/Brookhaven National Laboratory
The invention is essentially a micron-scale metallic marking grid upon which scientists place their samples -- biological tissues or inorganic samples such as minerals -- prior to imaging with different methods. "When the findings are analyzed, the grid can be used to 'map,' or orient, the images to one another, allowing us to study multiple variables in a single sample and better understand how they relate to one another," said biophysicist Lisa Miller, leader of the team that developed the new method.
For example, many diseases such as Alzheimer's are characterized by changes in both organic materials, such as proteins, as well as changes in the composition or concentration of inorganic trace metals (e.g., iron, copper, and zinc). Scientists have techniques -- infrared spectroscopy and x-ray fluorescence -- for studying each of these independently. But without a way to correlate the findings from the two methods, important information about the relationship between the organic and inorganic components can be missed.
"The x-ray and infrared-sensitive grid allows for the study of both pathological symptoms by precisely overlapping the results of these imaging methods," Miller said. "This ability to correlate images will ultimately lead to a more complete picture of many disease states."
The grid is deposited in two thicknesses onto an x-ray transparent material like mylar. It can be made of any metal, but gold is preferred. The "bars" of the grid are only a couple of nanometers thick, whereas the remainder of the metal surface is thicker. The dual thicknesses make the pattern sensitive to both infrared reflectivity and x-ray fluorescence imaging.
In another version of the invention, a single-layered grid is used to correlate light microscopy with x-ray fluorescence imaging.
Once the images are collected, custom software uses the grid patterns to align the images and correlate them with each other.
In addition to helping scientists study disease processes, the method could also be applied in monitoring and/or cleaning up environmental contamination, which is also characterized by the interplay of organic and inorganic factors.
This work was performed at Brookhaven Lab's National Synchrotron Light Source (NSLS), a source of intense infrared, ultraviolet, and x-ray beams used for studying atomic level details of a wide range of materials from biological molecules to semiconductor devices. Click here for more information on this study.
This project was funded by the National Institutes of Health with operational support for the NSLS provided by the Office of Basic Energy Sciences within the U.S. Department of Energy's Office of Science.
One of ten national laboratories overseen and funded primarily by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
Source: Karen McNulty Walsh
DOE/Brookhaven National Laboratory
вторник, 24 мая 2011 г.
Dementia Study Launched Within The Deaf Community
Researchers have launched a unique project to improve early diagnosis and management of dementia among Deaf people who use British Sign Language (BSL).
The research, funded by Alzheimer's Society, will examine how to identify dementia in Deaf people and explore how they might best cope with their condition. The study will also investigate how to provide support services for the Deaf community and develop assessment tools in BSL.
The University of Manchester team, working with colleagues at UCL (University College London), City University London, and the Royal Association for Deaf people, brings together Deaf and hearing researchers from a range of disciplines, including dementia care, social work, old-age psychiatry, psychology, Deaf studies and Sign Language research.
Lead researcher Professor Alys Young, from the Social Research with Deaf People programme at The University of Manchester, said: "Nobody knows whether Deaf people are more or less likely to experience dementia than hearing people. Our assumptions about what might be valued in care and support are based on hearing people's preferences, not rooted in an understanding of Deaf people's cultural experiences. Information about dementia and related services does not exist in Deaf people's preferred or only language BSL.
"There are no validated assessment tools in British Sign Language for diagnosis of dementia among Deaf people and using assessments designed for English speakers with an interpreter can lead to misunderstandings; some terms do not mean the same thing to people from different cultures."
The researchers will study normal ageing amongst Deaf signing people with the help of several hundred Deaf people who come together annually for a holiday organised by the English Deaf Darby and Joan Club. The team will also work with Deaf people with a diagnosis of dementia and their carers to explore their experiences of living with the illness, their priorities for care and how to improve early identification and support services.
Professor Bencie Woll, at UCL's Deafness, Cognition and Language research centre, where the BSL assessments will be developed, said: "Early identification of dementia brings many potential benefits, including access to medications, more time for people with dementia and their families to make decisions about care and support and the potential for a better quality of life.
"For Deaf people, the current lack of information in BSL and poor awareness in the Deaf community about dementia, combined with no diagnostic tools in BSL, means early identification is unlikely to happen. This research project aims to resolve that problem."
Professor Jane Marshall, at City University London, added: "The benefits of this project will be felt by Deaf people with dementia, their families and the health professionals who support people with this devastating diagnosis. The project should also add to our general understanding of dementia by studying its manifestations in a previously neglected language and cultural group."
Dr Susanne Sorensen, Head of Research at Alzheimer's Society, said:
"This exciting piece of research will, for the first time, look into the experiences of Deaf people with dementia. A person with dementia may have difficulty communicating and this can become a more complicated problem for Deaf people.
"The fact that many Deaf people struggle to get a diagnosis of dementia means that they're unable to access treatment that could help relieve some of their symptoms and enable them to remain independent for longer. One million people will develop dementia in the next 10 years. We must act now."
Source: Manchester University
The research, funded by Alzheimer's Society, will examine how to identify dementia in Deaf people and explore how they might best cope with their condition. The study will also investigate how to provide support services for the Deaf community and develop assessment tools in BSL.
The University of Manchester team, working with colleagues at UCL (University College London), City University London, and the Royal Association for Deaf people, brings together Deaf and hearing researchers from a range of disciplines, including dementia care, social work, old-age psychiatry, psychology, Deaf studies and Sign Language research.
Lead researcher Professor Alys Young, from the Social Research with Deaf People programme at The University of Manchester, said: "Nobody knows whether Deaf people are more or less likely to experience dementia than hearing people. Our assumptions about what might be valued in care and support are based on hearing people's preferences, not rooted in an understanding of Deaf people's cultural experiences. Information about dementia and related services does not exist in Deaf people's preferred or only language BSL.
"There are no validated assessment tools in British Sign Language for diagnosis of dementia among Deaf people and using assessments designed for English speakers with an interpreter can lead to misunderstandings; some terms do not mean the same thing to people from different cultures."
The researchers will study normal ageing amongst Deaf signing people with the help of several hundred Deaf people who come together annually for a holiday organised by the English Deaf Darby and Joan Club. The team will also work with Deaf people with a diagnosis of dementia and their carers to explore their experiences of living with the illness, their priorities for care and how to improve early identification and support services.
Professor Bencie Woll, at UCL's Deafness, Cognition and Language research centre, where the BSL assessments will be developed, said: "Early identification of dementia brings many potential benefits, including access to medications, more time for people with dementia and their families to make decisions about care and support and the potential for a better quality of life.
"For Deaf people, the current lack of information in BSL and poor awareness in the Deaf community about dementia, combined with no diagnostic tools in BSL, means early identification is unlikely to happen. This research project aims to resolve that problem."
Professor Jane Marshall, at City University London, added: "The benefits of this project will be felt by Deaf people with dementia, their families and the health professionals who support people with this devastating diagnosis. The project should also add to our general understanding of dementia by studying its manifestations in a previously neglected language and cultural group."
Dr Susanne Sorensen, Head of Research at Alzheimer's Society, said:
"This exciting piece of research will, for the first time, look into the experiences of Deaf people with dementia. A person with dementia may have difficulty communicating and this can become a more complicated problem for Deaf people.
"The fact that many Deaf people struggle to get a diagnosis of dementia means that they're unable to access treatment that could help relieve some of their symptoms and enable them to remain independent for longer. One million people will develop dementia in the next 10 years. We must act now."
Source: Manchester University
понедельник, 23 мая 2011 г.
Challenging NICE's Restriction For Alzheimer's Drugs May Be Attempt To Undermine Its Processes, UK
According to an editorial written by a senior health economist in this week's British Medical Journal (BMJ), a legal challenge against *NICE (National Institute for Health and Clinical Excellence) over its decision to limit the use of drugs for Alzheimer's disease could well be an attempt to undermine its processes.
* NICE is the body that decides what treatments are supplied on the National Health Service (NHS) in England and Wales.
NICE faces a judicial review over its refusal to make part of its modeling data for the dementia drug donepezil (Aricept) available to the pharmaceutical industry. NICE insists it is crucial to protect the intellectual property rights of external assessment groups, such as the Southampton University's Health Technology Centre. Alan Maynard, Professor of Health Economics at York University, says that NICE's protection of just this part of the assessment process may be unwise - even though this lack of transparency has never been challenged before.
Maynard says that this conflict may be an attempt by the pharmaceutical industry to improve its profits from a marginally cost effective drug, and could also be part of a more subtle drive to undermine processes of assessing health technology, which are designed to make sure taxpayers receive effective treatment which is good value for money.
Maynard says similar attempts to undermine the process have also taken place in Australia, which has a similar system of assessing the cost-effectiveness of drugs and devices.
Maynard argues that NICE is essential for improving the efficiency of the NHS. He adds that NICE's processes are generally sensible and transparent. He also writes that the constraints under which it works can be improved.
Maynard writes "Surely it would have been better to have compensated Southampton for its loss of property rights in its model of treatment for Alzheimer's disease rather than become entangled in litigation. With the NHS seeking to control expenditure and target the use of drugs to improve the health of the population in a cost effective manner, and industry wanting to maximise its profits, conflict is inevitable. It is essential that the trade off between health and wealth is managed with transparent and good science by all participants - both public and private."
"Transparency in health technology assessments"
Editorial
BMJ Volume 334 pp 594-5
bmj
Edited by:
View drug information on ARICEPT.
* NICE is the body that decides what treatments are supplied on the National Health Service (NHS) in England and Wales.
NICE faces a judicial review over its refusal to make part of its modeling data for the dementia drug donepezil (Aricept) available to the pharmaceutical industry. NICE insists it is crucial to protect the intellectual property rights of external assessment groups, such as the Southampton University's Health Technology Centre. Alan Maynard, Professor of Health Economics at York University, says that NICE's protection of just this part of the assessment process may be unwise - even though this lack of transparency has never been challenged before.
Maynard says that this conflict may be an attempt by the pharmaceutical industry to improve its profits from a marginally cost effective drug, and could also be part of a more subtle drive to undermine processes of assessing health technology, which are designed to make sure taxpayers receive effective treatment which is good value for money.
Maynard says similar attempts to undermine the process have also taken place in Australia, which has a similar system of assessing the cost-effectiveness of drugs and devices.
Maynard argues that NICE is essential for improving the efficiency of the NHS. He adds that NICE's processes are generally sensible and transparent. He also writes that the constraints under which it works can be improved.
Maynard writes "Surely it would have been better to have compensated Southampton for its loss of property rights in its model of treatment for Alzheimer's disease rather than become entangled in litigation. With the NHS seeking to control expenditure and target the use of drugs to improve the health of the population in a cost effective manner, and industry wanting to maximise its profits, conflict is inevitable. It is essential that the trade off between health and wealth is managed with transparent and good science by all participants - both public and private."
"Transparency in health technology assessments"
Editorial
BMJ Volume 334 pp 594-5
bmj
Edited by:
View drug information on ARICEPT.
воскресенье, 22 мая 2011 г.
Metabolon Extends Biochemical Understanding Of Alzheimers Disease
Metabolon, Inc., leaders in global metabolomics, biomarker discovery and biochemical analysis, announces the publication of "Ablation of the Locus Coeruleus (LC) Increases Oxidative Stress in Tg-2576 Transgenic But Not Wild-type Mice" in the International Journal of Alzheimer Disease. The paper examines the role of the LC on markers of oxidative stress in transgenic mice and was carried out as a collaboration among scientists at Pfizer, Proteostasis Therapeutics, the University of Dundee, Duke University and Metabolon. The paper is co-authored by Orest Hurko, Kurt Boudonck, Cathleen Gonzalez, J. Steve Jacobsen, Peter H. Reinhart, Crowther Daniel, Zoe A. Hughes.
Previous research in this area suggested that differences in inflammatory response observed in humans with Alzheimer disease and mouse models reflect a discrepancy in the state of the LC, the major site of norepinephrine synthesis in the brain. LC degeneration is an early change in human Alzheimer disease, but it is preserved in transgenic mouse models of Alzheimer disease. The authors use a non-targeted metabolomic approach to examine the effects of ablating the LC on oxidative stress and intermediary metabolism. Mice transgenic for beta-amyloid (Tg2576A??) in which the LC had been ablated showed greater concordance with human Alzheimer disease, including increased oxidative stress and altered energy metabolism. The results support the proposal that LC degeneration may contribute to key pathophysiological features of Alzheimer disease, and extend the hypothesis from inflammation to oxidative stress and altered carbohydrate metabolism. Moreover, transgenic mice with an LC ablation may provide a more congruent model for human Alzheimer disease than transgenic mice with intact LC.
Source:
Metabolon, Inc.
Previous research in this area suggested that differences in inflammatory response observed in humans with Alzheimer disease and mouse models reflect a discrepancy in the state of the LC, the major site of norepinephrine synthesis in the brain. LC degeneration is an early change in human Alzheimer disease, but it is preserved in transgenic mouse models of Alzheimer disease. The authors use a non-targeted metabolomic approach to examine the effects of ablating the LC on oxidative stress and intermediary metabolism. Mice transgenic for beta-amyloid (Tg2576A??) in which the LC had been ablated showed greater concordance with human Alzheimer disease, including increased oxidative stress and altered energy metabolism. The results support the proposal that LC degeneration may contribute to key pathophysiological features of Alzheimer disease, and extend the hypothesis from inflammation to oxidative stress and altered carbohydrate metabolism. Moreover, transgenic mice with an LC ablation may provide a more congruent model for human Alzheimer disease than transgenic mice with intact LC.
Source:
Metabolon, Inc.
суббота, 21 мая 2011 г.
Elan And Transition Therapeutics Announce Phase 1 Data Showing ELND005 Achieves Desired Concentrations In Brain Tissue And Cerebrospinal Fluid
Elan Corporation, plc (NYSE: ELN) and Transition Therapeutics Inc. (TSX: TTH, NASDAQ: TTHI) today presented Phase 1 data demonstrating that treatment with ELND005 (scyllo-inositol formerly known as AZD-103), achieves desired concentrations in human brain tissue and cerebrospinal fluid when given orally. Preclinical data also were presented showing that ELND005 administration is associated with preservation of choline acetyltransferase (ChAT), reflecting preservation of nerve cells that are critical to memory function in the brain. ELND005 is an orally-administered drug candidate in Phase 2 trials for the treatment of mild to moderate Alzheimer's disease. These results were presented at the 2009 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD 2009) in Vienna, Austria.
In a poster entitled, "Oral Amyloid Anti-aggregating Agent ELND005 is Measurable in CSF and Brain of Healthy Adult Men," the researchers describe results of a Phase 1 study in which eight healthy adults each received 2,000 mg of ELND005 twice a day for 10 days. Concentrations of ELND005 in cerebrospinal fluid were measured directly, while brain tissue concentrations were measured non-invasively using a novel magnetic resonance spectroscopy technique and were determined to be within the range associated with efficacy in previous animal studies that employed a transgenic animal model of Alzheimer's Disease. ELND005 was well tolerated by these study participants with no severe, serious, or treatment-limiting adverse events observed.
"Achieving a clinically beneficial concentration of drug in brain tissue and cerebrospinal fluid has presented a significant hurdle to other drugs investigated to treat Alzheimer's Disease, so this is an important proof of concept for us," said Elan president Carlos V. Paya, MD, PhD. "We look forward to completing and reporting results from our ongoing Phase 2 study of ELND005 in patients with mild to moderate Alzheimer's disease, which completed enrollment in October 2008."
In a second poster, entitled "Quantification of Cholinergic Degradation and Adult Neurogenesis in TgCRND8 Mice Following Treatment with Scyllo-Inositol (ELND005)," Dr. JoAnne McLaurin and colleagues from the University of Toronto analyzed levels of the enzyme Choline Acetyltransferase (ChAT) in an animal model of Alzheimer's disease. As in humans, these Alzheimer's animal models exhibit damage to nerve cells in a region of the brain called the "basal forebrain" that use the neurotransmitter acetylcholine to transmit nerve impulses critical to memory functions to other nerve cells in a brain region important for memory function called the hippocampus. Animals treated with ELND005 exhibited significantly more ChAT levels compared to untreated animals.
"There is evidence that amyloid plaque formation drives the decline in memory and cognition associated with Alzheimer's disease," said JoAnne McLaurin, PhD, professor at the University of Toronto's Centre for Research in Neurodegenerative Diseases. "Although more research is necessary, the findings presented today suggest that ELND005 may have the ability to prevent the loss of ChAT that results from damage to cholinergic neurons in the brain, thereby potentially protecting against cognitive decline in individuals with Alzheimer's disease."
"We have conducted a robust preclinical and Phase 1 research program of ELND005 that has demonstrated that the drug is able to cross the blood-brain barrier, which should allow it to target the disaggregation of amyloid beta in the brain," said Dr. Tony Cruz, chairman and chief executive officer of Transition.
In 2006, Elan and Transition entered into an exclusive, worldwide collaboration agreement for the joint development and commercialization of ELND005 for the treatment of Alzheimer's disease and other indications.
About ELND005 (AZD-103)
ELND005 is an orally-administered therapeutic agent that has received fast track designation from the U.S. Food and Drug Administration (FDA) for treatment of mild to moderate Alzheimer's disease. Fast track designation can facilitate development and may expedite regulatory review of drugs that the FDA recognizes as potentially addressing an unmet medical need for serious or life-threatening conditions.
ELND005 is currently in a Phase 2 clinical study, which completed enrollment in October 2008. The study is a randomized, double-blind, placebo-controlled, dose-ranging, safety and efficacy study in approximately 340 patients with mild to moderate Alzheimer's disease. The planned treatment period for each patient is approximately 18 months.
About Alzheimer's Disease
Alzheimer's disease, a leading cause of dementia, is a progressive brain disorder that gradually destroys a person's memory and ability to learn, reason, make judgments, communicate and carry out daily activities. Alzheimer's disease may result from the build-up of toxic beta-amyloid peptides in the brain. As Alzheimer's disease progresses, individuals may also experience changes in personality and behavior, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations. It is currently estimated that more than 5 million Americans have Alzheimer's disease and more than 24 million people worldwide over the age of 60 have some form of dementia (Source: Alzheimer's Association and Alzheimer's Disease International).
About Elan
Elan Corporation, plc is a neuroscience-based biotechnology company committed to making a difference in the lives of patients and their families by dedicating itself to bringing innovations in science to fill significant unmet medical needs that continue to exist around the world. Elan shares trade on the New York, London and Dublin Stock Exchanges. For additional information about the company, please visit elan.
Source
Transition
In a poster entitled, "Oral Amyloid Anti-aggregating Agent ELND005 is Measurable in CSF and Brain of Healthy Adult Men," the researchers describe results of a Phase 1 study in which eight healthy adults each received 2,000 mg of ELND005 twice a day for 10 days. Concentrations of ELND005 in cerebrospinal fluid were measured directly, while brain tissue concentrations were measured non-invasively using a novel magnetic resonance spectroscopy technique and were determined to be within the range associated with efficacy in previous animal studies that employed a transgenic animal model of Alzheimer's Disease. ELND005 was well tolerated by these study participants with no severe, serious, or treatment-limiting adverse events observed.
"Achieving a clinically beneficial concentration of drug in brain tissue and cerebrospinal fluid has presented a significant hurdle to other drugs investigated to treat Alzheimer's Disease, so this is an important proof of concept for us," said Elan president Carlos V. Paya, MD, PhD. "We look forward to completing and reporting results from our ongoing Phase 2 study of ELND005 in patients with mild to moderate Alzheimer's disease, which completed enrollment in October 2008."
In a second poster, entitled "Quantification of Cholinergic Degradation and Adult Neurogenesis in TgCRND8 Mice Following Treatment with Scyllo-Inositol (ELND005)," Dr. JoAnne McLaurin and colleagues from the University of Toronto analyzed levels of the enzyme Choline Acetyltransferase (ChAT) in an animal model of Alzheimer's disease. As in humans, these Alzheimer's animal models exhibit damage to nerve cells in a region of the brain called the "basal forebrain" that use the neurotransmitter acetylcholine to transmit nerve impulses critical to memory functions to other nerve cells in a brain region important for memory function called the hippocampus. Animals treated with ELND005 exhibited significantly more ChAT levels compared to untreated animals.
"There is evidence that amyloid plaque formation drives the decline in memory and cognition associated with Alzheimer's disease," said JoAnne McLaurin, PhD, professor at the University of Toronto's Centre for Research in Neurodegenerative Diseases. "Although more research is necessary, the findings presented today suggest that ELND005 may have the ability to prevent the loss of ChAT that results from damage to cholinergic neurons in the brain, thereby potentially protecting against cognitive decline in individuals with Alzheimer's disease."
"We have conducted a robust preclinical and Phase 1 research program of ELND005 that has demonstrated that the drug is able to cross the blood-brain barrier, which should allow it to target the disaggregation of amyloid beta in the brain," said Dr. Tony Cruz, chairman and chief executive officer of Transition.
In 2006, Elan and Transition entered into an exclusive, worldwide collaboration agreement for the joint development and commercialization of ELND005 for the treatment of Alzheimer's disease and other indications.
About ELND005 (AZD-103)
ELND005 is an orally-administered therapeutic agent that has received fast track designation from the U.S. Food and Drug Administration (FDA) for treatment of mild to moderate Alzheimer's disease. Fast track designation can facilitate development and may expedite regulatory review of drugs that the FDA recognizes as potentially addressing an unmet medical need for serious or life-threatening conditions.
ELND005 is currently in a Phase 2 clinical study, which completed enrollment in October 2008. The study is a randomized, double-blind, placebo-controlled, dose-ranging, safety and efficacy study in approximately 340 patients with mild to moderate Alzheimer's disease. The planned treatment period for each patient is approximately 18 months.
About Alzheimer's Disease
Alzheimer's disease, a leading cause of dementia, is a progressive brain disorder that gradually destroys a person's memory and ability to learn, reason, make judgments, communicate and carry out daily activities. Alzheimer's disease may result from the build-up of toxic beta-amyloid peptides in the brain. As Alzheimer's disease progresses, individuals may also experience changes in personality and behavior, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations. It is currently estimated that more than 5 million Americans have Alzheimer's disease and more than 24 million people worldwide over the age of 60 have some form of dementia (Source: Alzheimer's Association and Alzheimer's Disease International).
About Elan
Elan Corporation, plc is a neuroscience-based biotechnology company committed to making a difference in the lives of patients and their families by dedicating itself to bringing innovations in science to fill significant unmet medical needs that continue to exist around the world. Elan shares trade on the New York, London and Dublin Stock Exchanges. For additional information about the company, please visit elan.
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