PLEASE NOTE: To reply to any of the postings to this Topic, "Requests Prior to March 2007," please contact:

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Seeking Collaborators—Posted 3 January 2007

ExonHit Therapeutics is a world-leading biotech company in the field of alternative RNA splicing, a process which when deregulated plays a key role in various diseases. We have a special interest in some identified splicing variants differentially implicated in APP processing. We are interested in mapping the expression profile of such splicing variants during aging and Alzheimer disease.

We are seeking collaboration with a laboratory having easy access to brain biopsies of Alzheimer patients and normal, undemented, age-matched control individuals, which would be interested in a collaborative work for publication purpose.

The overall aim of this study is to study and document both the expression profile in various parts of the brain (by Western blot and immunohistochemistry using our available variant-specific antibodies) and the function on APP processing of such splicing variants during aging and Alzheimer disease.—Dr. Laurent Desire, Director Neurology

Seeking Collaborators—Posted 10 March 2006
Although Alzheimer's disease (AD) has now become one of the biggest public health issues in the first world, its definitive diagnosis still depends on the postmortem observation of neurofibrillary tangles (NFTs), which correlate in density and localization with the progression of clinical symptoms. The mechanism of NFT formation in AD is not clear. But since they are composed of aggregates of hyperphosphorylated tau protein, the search for AD-specific tau kinases has been a subject of intense study. Tau kinases may indeed be the molecular integrators of various signaling pathways, and characterization of AD-specific kinase activities may elucidate the mechanisms involved in AD-associated factors such as age, oxidative stress, increased amyloid production, and cell cycle activation. Furthermore, identification of tau kinases involved in AD pathology will yield drug targets for combating this disease.

Recently, our two research groups in the Karolinska Institute, Stockholm (KI) and the Centro de Biologia Molecular "Severo Ochoa," Madrid (CBMSO) have joined forces to determine the role of a novel kinase cascade in AD pathology. This cascade comprises targets still new to AD pharma-industry such as mTOR and p70 S6 kinase (p70S6K) as well as targets already under intense study, such as glycogen synthase kinase (GSK3). The KI group, headed by Jin-Jing Pei, entered the AD field in 1993 via the field of human brain pathology, while Filip Lim (CBMSO) first began AD research in 1995 as an application for his work with gene transfer in the nervous system. The diverse skills and know-how of the two groups are highly complementary in view of the fact that they have now converged toward a common goal of using genetically manipulated animal and cell models to determine the mechanism of tauopathic neurodegeneration in AD. Between Stockholm and Madrid, we have a wide range of resources and techniques including cDNA expression plasmids for numerous protein kinases, lenti- and herpes- viral vectors, neuronal cell lines and primary cultures, brain slice cultures, transgenic mice, stereotaxic injection, behavioral tests, histological and biochemical analyses, access to human brain banks. We are now looking for industrial partners with an interest in identifying targets for pharmacological intervention for AD therapy (full project details and disclosure agreement on request).—Main investigators: Jin-Jing Pei and Filip Lim

Seeking Collaborators.—Posted 6 October 2004
Desperately seeking for SH-SY5Y-APP transgenic cells. Who would like to share these cells with us and collaborate on lipid homeostasis and AD?—Gunter Eckert, Ph.D., Web site: http://www.biozentrum.uni-frankfurt.de/Pharmakologie/ Seeking Collaborators.—Posted 12 April 2004
Perlegen Sciences, a leader in pharmacogenomics, is seeking collaborations with companies and research institutes that have conducted large Alzheimer clinical trials that were subsequently discontinued. Using high-speed technology to sequence entire human genomes, Perlegen researchers are analyzing single-nucleotide polymorphisms (SNPs) in thousands of people to identify which SNPs can be used to optimize treatment with today’s drugs, and which can point researchers to the underlying causes of disease to develop tomorrow’s drugs.

Perlegen is currently collaborating with several of the world’s largest pharmaceutical companies to help identify SNP patterns that affect drug responses and to use that knowledge to deliver safer, more effective drugs to consumers. We have a special interest in drugs that failed in clinical trials but which demonstrated a positive effect in a subset of patients.

If you are a clinician, CRO, pharmaceutical or biotech researcher or manager who has participated in such trials for Alzheimer’s, we would like to hear from you. Perlegen is actively looking for Alzheimer’s drug candidates that could benefit from the company’s pharmacogenomics technology. Ideally, these would be drugs for which blood samples were collected for genetic analysis during clinical trials, but for which development later stalled or was discontinued despite showing promise in earlier trials.—Dr. Raquel Izumi, Director of Clinical Development

Desperately seeking donations of unwanted APP transgenic and littermate control animals.—Posted 19 February 2004
No age restrictions, no questions asked, no strings attached. We pay shipping!—Mark A. Smith

Seeking Collaborators—Posted 24 October 2003
We are a chemistry group involved in an AD research program, looking for a collaboration with an academic team with expertise in the in vivo screening of γ-secretase inhibitors in transgenic mice. We have now evidence that some of our new inhibitors are promising γ-secretase inhibitors in vitro (cell-free assay and cell-based assay on cells overexpressing APP, swedish mutation have been positively performed). The next step should be to perform in vivo animal studies on Tg 2576 mice overexpressing APP695NL. We would like to screen only two compounds (the parent drug and its new prototype) in order to validate our concept.

The suggested in vivo study could be the following: After 3 days orally feeding, from the brain of these Tg 2576 mice, a compared analysis of the production of Aβ-40 and Aβ-42 by ELISA method, between the 2 compounds (parent drug and the new analogue) will give us the answer to validate our new chemical concept. If an academic lab is interested to help us to achieve this in vivo study, we can consider common publication. Thank you for your help.—Kraus

Seeking Collaborators—Posted 19 June 2003
A new national project to study the cultural dimensions of Alzheimer's disease is seeking researchers who are employing methods from oral history and/or narrative medicine to interview Alzheimer patients who are World War II veterans. The project is interested both in the content of these interviews and in the therapeutic potential of the interview experience. Please contact Michael Verde.

Seeking Collaborators—Posted 1 April 2003
I am a doctoral student named Danita Ewing studying family nursing at Oregon Health and Science University. I am conducting a study of family caregivers that use the Internet to support their caregiving. The purpose of the study is to learn how using the Internet is or is not benefiting family caregivers in order to design web sites for caregivers which can help meet their needs. Please visit the study website at http://www.familycaregiverinternetstudy.net/ to learn more about the opportunity to participate in this study.—Danita Ewing

Seeking Collaborators—Posted 24 September 2002
Do you have any autopsy-confirmed cases of "plaque-only" or "plaque-dominated" presenile dementia (age of onset before 65) that you would like to see analyzed further? Hans Kluenemann and colleagues at the University of Regensburg Medical School are looking for such cases to complete their study of an extensive pedigree of one of Alois Alzheimer's original patients, and to perform a clinico-pathologic correlation with other families. All contributors will have the option of co-authoring the resulting article.—Hans Kluenemann

Seeking Collaborators—Posted 22 August 2002
I am a Head of Geriatric Service in the oldest municipality at Havana City, Cuba. I am very interested to introduce clinical and psychological testing in old people and demented people, mainly with vascular dementia. I am sure that we can do something together.—Cordially, Dr. Maria Caridad Machado Porro

Seeking Collaborators to help develop novel test battery—Posted 8 July 2002
I have a PhD in neuropsychology and have done research on different types of fluency in Alzheimer's and other geriatric patients. Findings are that two factors underlie the performance in letter based fluency, one intial semiautomatic and one effortful retrieval factor (late). These factors are seen in cognitive decline due to dementia. In category fluency basically one factor is measured, access to semantic memory. I have also used factor analysis to find out what WAIS-Similarities and Rey-AVLT-learning measure and correlated factor scores with white or grey matter atrophy. Today I am developing more efficient tests for use in memory investigations and dementia diagnosis. The method I am using is called the staircase method because it is based on an additive model of stages of processing.

I am working privately with the development of the test battery I mentioned. My affiliation is with Department of Psychology, Stockholm University, Sweden. The patient groups which are of special interest to me are Alzheimer's, frontotemporal dementia, ADHD and semantic dementia. Those people or organizations interested in collabaoration must be interested in the application of modern cognitive science to the neuropsychological diagnostic work. At the moment I do some teaching at KI, Stockholm, but I would like to work abroad, in Netherlands, UK or Canada. My specific contribution would be expertise in multivariate statistics, database managing, test development, clinical testing, mnemonic training and teaching in cognition and differential dementia diagnostics.—Sven-Erik Fernaeus

Response—Posted 27 September 2002

We have been working on some of the issues you mention above. You can see my work at: www.medafile.com, particularly we are working on developing an on-line test. I have also been working on developing a screening test which uses animal naming.

However, you may be more interested in the work at: www.alzheimersscreen.com. They are putting a more standard neuropsychological battery into a computer format.

In any case, your work is definitely related to what we are trying to do. My own interest is implementing Item Response Theory, and I am currently trying to apply data to the analysis of the Mini-mental State Exam, on the web (preliminary version is on medafile.com, with a calculation for the severity of illness based on "time", but the IRT is not running yet). collaboration, or even discussion about our developments.—Wes Ashford