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
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.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 498.81K | Year: 2008
DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with more than 4.5 million Americans currently suffering from the disease. Clinical management of AD is complicated by lack of effective meth ods for early and accurate diagnosis of the disease. Thus, there is a significant unmet need for Alzheimer's disease diagnostic tools. The hypothesis of this project is that positron emission computed tomography (PET) imaging of pathological tau fibrils wo uld provide an excellent biomarker for detection of tau pathology useful for both 1) Staging and monitoring progression of Alzheimer's disease and for 2) Improving early and accurate diagnosis of Alzheimer's and related tauopathies. To test this hypothesis , we will screen for and develop a novel 18F-labeled radiopharmaceutical to specifically and sensitively bind tau fibrils (the chief constituent of neurofibrillary tangles in Alzheimer's). Working with our collaborators, we have recently demonstrated a suc cessful human proof of mechanism clinical trial for an amyloid plaque imaging agent. The tau imaging agent proposed here would provide a valuable complement to this amyloid agent by allowing for imaging of the two primary pathologies in Alzheimer's disease . Furthermore, the expertise we have developed on the amyloid project (which was also funded through SBIR grants) can now be directly applied to developing the tau specific agent. Thus Phase I of this project will now assess the feasibility of developing a tau agent by in vitro and mouse testing of multiple families of small molecules that we have developed. Phase II will test the characteristics of the biomarker proof of mechanism trials in patients under an exploratory IND. Successful accomplishment of th ese studies will yield an innovative radiopharmaceutical product for the evaluation and diagnosis of AD. A widely available imaging test for tau pathology in AD will yield significant scientific, commercial and societal benefits. PUBLIC HEALTH RELEVANCE: A lzheimer's disease (AD) is the most common cause of dementia in the elderly, with more than 4.5 million Americans currently suffering from the disease. Clinical management of AD and related diseases (including fronto-temporal dementia) is complicated by la ck of effective methods for early and accurate diagnosis and monitoring of disease progression. Successful accomplishment of this project will provide a tau specific molecular imaging agent. When used in conjunction with amyloid specific molecular imaging agents (such as the one Avid is already developing, supported by SBIR funding) the tau specific agent would represents a significant advance towards meeting these goals for accurate diagnosis and monitoring of AD and related diseases.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 507.50K | Year: 2008
DESCRIPTION (provided by applicant): Dementia associated with PD (PDD) is common (affecting up to 80% of patients long-term) and highly disabling. Informative biomarkers are urgently needed to understand the pathology of PDD, to improve the early detection of cognitive deficits and to facilitate the development of treatments for PDD. Nuclear imaging technologies have the potential to produce such biomarkers. Numerous studies have used 11C-PIB to measure amyloid burden in Alzheimer's disease (AD) and other d ementing illnesses. However, the experience with amyloid imaging in PD has been limited, in spite of post-mortem evidence for substantial amyloid deposition in patients with PD. One of the impediments to conducting additional studies with 11C-PIB has been the short half life of 11C (H20 min), necessitating an on-site cyclotron and in-house radiochemistry expertise. Since the PET isotope 18F has a 110 minute half life and a well established nationwide distribution network, it has been our long standing corpo rate goal to develop an 18F amyloid imaging agent for amyloid plaques. We have recently developed and validated in human trials such an agent, 18F-AV-45, which is easy to use, can be made cheaply and reliably, and can be distributed on a regional basis. Mo st importantly, the compound shows an excellent ability (as good as or better than 11C-PIB) to image amyloid plaques in Alzheimer's disease. In this STTR grant we propose to conduct the first ever clinical trial of 18F-AV-45 in PD patients. The over-archin g aim of this study is to use 18F-AV-45 imaging of amyloid burden as a biomarker to test the relationship between amyloid burden and cognitive functioning in PD. We will image 25 PD subjects over 2 years with 18F-AV-45 and will compare imaging results with clinical data and CSF biomarkers (tau and a-beta) of amyloid pathology. We hypothesize that 18F-AV-45 binding will be associated with greater degrees of overall cognitive impairment, shorter interval between onset of motor and cognitive impairment, and pa ttern of CSF biomarkers reflecting amyloid pathology. PUBLIC HEALTH RELEVANCE: Successful validation of amyloid imaging as a biomarker for cognitive impairment in Parkinson's disease (PD) would represent a significant milestone in improving the diagnosis a nd treatment of this highly disabling feature of PD, and would represent a significant commercial opportunity for molecular imaging of these patients. However, little information is currently available regarding the amyloid burden, as measured by molecular imaging, in patients with PD or dementia associated with PD (PDD). 18F-AV- 45 is a fluorinated PET isotope that has favorable properties and has been shown to accurately identify amyloid pathology in Alzheimer's patients. In this project, we propose to us e 18F-AV-45 to image amyloid pathology in patients with PD with cognitive impairment for the first time. Avid Radiopharmaceuticals is an experienced leader in developing new commercial PET tracers and is collaborating with world-experts on cognitive impair ment in PD to conduct this clinical trial of amyloid imaging in PD and PDD.
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.