Avid Radiopharmaceuticals is an American company, founded by Dr. Daniel Skovronsky, and based at the University City Science Center research campus in Philadelphia, Pennsylvania. The company has developed a radioactive tracer called florbetapir . Florbetapir can be used to detect beta amyloid plaques in patients with memory problems using positron emission tomography scans, making the company the first to bring to market an FDA-approved method that can directly detect this hallmark pathology of Alzheimer's disease. Venture investors include Alta Partners, Osage University Partners, and Safeguard Scientifics.Eli Lilly and Company announced on November 8, 2010, that they would acquire Avid for $800 million, with $300 million paid out up front and the balance paid later on. Wikipedia.
Hao J.,Eli Lilly and Company |
Xiong H.,Avid Radiopharmaceuticals
Current Topics in Medicinal Chemistry | Year: 2014
Metabotropic glutamate receptor 5 (mGlu5) is a class C G-protein-coupled receptor which possesses a large extracellular N-terminal domain (ATD) connected to the seven-transmembrane (7-TM) domain. In contrast to the glutamate and its close analogs binding at the orthosteric site on the ATD region, allosteric modulators bind at topographically distinct sites in the 7-TM region. Activation of mGlu5 receptors at either the orthosteric or allosteric sites results in enhancement of NMDA receptor function and represents a promising opportunity for the treatment of schizophrenia. Since the disclosure of the first mGlu5 positive allosteric modulators (PAM) in 2003, there have been intense industry-wide efforts to discover and develop safe and efficacious agents capable of selectively enhancing mGlu5 receptor function at the allosteric sites. Over the past decade, tremendous progress has been made, and multiple chemical scaffolds have been identified as mGlu5 PAMs, possibly binding to different allosteric sites on the 7-TM domain. These ligands have helped gain novel insights into the biology of mGlu5 receptor allosteric activation. Here we provide a comprehensive review on the structure-activity relationship (SAR) progress on the mGlu5 PAMs reported in the primary literature and include appropriate and complementary examples from the patent literature. Important in vivo studies of select compounds from individual scaffolds are highlighted, and challenges facing the clinical development of mGlu5 receptor PAMs are discussed. © 2014 Bentham Science Publishers Source
Jennings D.,Institute for Neurodegenerative Disorders |
Siderowf A.,Avid Radiopharmaceuticals |
Stern M.,University of Pennsylvania |
Seibyl J.,Institute for Neurodegenerative Disorders |
And 3 more authors.
Neurology | Year: 2014
Objectives: The purpose of this study is to evaluate the relative risk of abnormal dopamine transporter (DAT) imaging for subjects with and without hyposmia and the feasibility of acquiring a large, community-based, 2-tiered biomarker assessment strategy to detect prodromal Parkinson disease (PD). Methods: In this observational study, individuals without a diagnosis of PD, recruited through 16 movement disorder clinics, underwent tier 1 assessments (olfactory testing, questionnaires). Tier 2 assessments (neurologic examination, DAT imaging, and other biomarker assessments) were completed by 303 subjects. The main outcome of the study is to compare age-expected [123I]b-CIT striatal binding ratio in hyposmic and normosmic subjects. Results: Tier 1 assessments were mailed to 9,398 eligible subjects and returned by 4,999; 669 were hyposmic. Three hundred three subjects (203 hyposmic, 100 normosmic) completed baseline evaluations. DAT deficit was present in 11%of hyposmic subjects compared with 1% of normosmic subjects. Multiple logistic regression demonstrates hyposmia (odds ratio [OR] 12.4; 95% confidence interval [CI] 1.6, 96.1), male sex (OR 5.5; 95% CI 1.7, 17.2), and constipation (OR 4.3; 95% CI 1.6, 11.6) as factors predictive of DAT deficit. Combining multiple factors (hyposmia, male sex, and constipation) increased the percentage of subjects with a DAT deficit to .40%. Conclusion: Subjects with DAT deficit who do not meet criteria for a diagnosis of PD can be identified by olfactory testing. Sequential biomarker assessment may identify those at risk of PD. Selecting hyposmic individuals enriches the population for DAT deficit, and combining hyposmia with other potential risk factors (male sex, constipation) increases the percentage of subjects with a DAT deficit compatible with prodromal PD. © 2014 American Academy of Neurology. Source
Roe C.M.,University of Washington |
Fagan A.M.,University of Washington |
Grant E.A.,University of Washington |
Hassenstab J.,University of Washington |
And 8 more authors.
Neurology | Year: 2013
Objectives: We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ 42, tau, ptau181, tau/Aβ42, ptau 181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years. Methods: Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. "Expanded" models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared. Results: Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p > 0.074), nor did we find differences between the expanded biomarker models (p > 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p < 0.005). Conclusions: Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms. © 2013 American Academy of Neurology. Source
Su Y.,University of Washington |
Arbelaez A.M.,University of Washington |
Benzinger T.L.S.,University of Washington |
Snyder A.Z.,University of Washington |
And 3 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2013
Positron emission tomography (PET) with 15 O-labeled water can provide reliable measurement of cerebral blood flow (CBF). Quantification of CBF requires knowledge of the arterial input function (AIF), which is usually provided by arterial blood sampling. However, arterial sampling is invasive. Moreover, the blood generally is sampled at the wrist, which does not perfectly represent the AIF of the brain, because of the effects of delay and dispersion. We developed and validated a new noninvasive method to obtain the AIF directly by PET imaging of the internal carotid artery in a region of interest (ROI) defined by coregistered high-resolution magnetic resonance angiography. An ROI centered at the petrous portion of the internal carotid artery was defined, and the AIF was estimated simultaneously with whole brain blood flow. The image-derived AIF (IDAIF) method was validated against conventional arterial sampling. The IDAIF generated highly reproducible CBF estimations, generally in good agreement with the conventional technique. © 2013 ISCBFM All rights reserved. Source
Landau S.M.,University of California at Berkeley |
Landau S.M.,Lawrence Berkeley National Laboratory |
Landau S.M.,Avid Radiopharmaceuticals |
Mintun M.A.,Avid Radiopharmaceuticals |
And 7 more authors.
Annals of Neurology | Year: 2012
Objective: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross-sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements. Methods: We examined associations between mean cortical florbetapir uptake, mean 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS-cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients). For a subset of these (76 normal, 81 LMCI) we determined whether florbetapir and FDG-PET were associated with retrospective decline in longitudinal ADAS-cog measurements. Results: Twenty-nine percent of normal subjects, 43% of EMCI patients, 62% of LMCI patients, and 77% of AD patients were categorized as florbetapir positive. Florbetapir was negatively associated with concurrent FDG and ADAS-cog in both MCI groups. In longitudinal analyses, florbetapir-positive subjects in both normal and LMCI groups had greater ongoing ADAS-cog decline than those who were florbetapir negative. However, in normal subjects, florbetapir positivity was associated with greater ADAS-cog decline than FDG, whereas in LMCI, FDG positivity was associated with greater decline than florbetapir. Interpretation: Although both hypometabolism and β-amyloid (Aβ) deposition are detectable in normal subjects and all diagnostic groups, Aβ showed greater associations with cognitive decline in normal participants. In view of the minimal cognitive deterioration overall in this group, this suggests that amyloid deposition has an early and subclinical impact on cognition that precedes metabolic changes. At moderate and later stages of disease (LMCI/AD), hypometabolism becomes more pronounced and more closely linked to ongoing cognitive decline. ANN NEUROL 2012;72:578-586 Copyright © 2012 American Neurological Association. Source