BrainBlog

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study of the Oral γ-Secretase Inhibitor BMS-708163 (Avagacestat): Tolerability Profile, Pharmacokinetic Parameters, and Pharmacodynamic Markers Clin Ther. 2012 Feb 28; Tong G, Wang JS, Sverdlov O, Huang SP, Slemmon R, Croop R, Castaneda L, Gu H, Wong O, Li H, Berman RM, Smith C, Albright CF, Dockens RC Abstract BACKGROUND: γ-Secretase inhibitors (GSIs) are being investigated for their potential to modify the progression of Alzheimer disease based on their ability to regulate amyloid-β (Aβ) accumulation. BMS-708163 (avagacestat) is an oral GSI designed for selective inhibition of Aβ synthesis currently in development for the treatment of mild to moderate and predementia AD. In addition to the desired effect on Aβ synthesis, GSIs affect Notch processing, which is thought to mediate some toxic adverse effects reported with this drug class. Avagacestat produced up to 190-fold greater selectivity for Aβ synth...

The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. American Journal of Psychiatry. 2011 Dec;168(12):1266-77. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. Abstract Research on suicide prevention and interventions requires a standard method for assessing both suicidal ideation and behavior to identify those at risk and to track treatment response. The Columbia-Suicide Severity Rating Scale (C-SSRS) was designed to quantify the severity of suicidal ideation and behavior. The authors examined the psychometric properties of the scale. The C-SSRS's validity relative to other measures of suicidal ideation and behavior and the internal consistency of its intensity of ideation subscale were analyzed in three multisite studies: a treatment study of adolescent suicide attempters (N=124); a medication efficacy trial wit...

An interesting read. I always aimed for 6th-grade reading level myself, so it surprised me to read of this finding: Informed Consent Forms Target 11th Grade Readers By Ed Silverman Pharmalot December 12th, 2011 // 9:29 am Read the full blog post

From Bloomberg : Eli Lilly Shares Rise on Alzheimer’s Drug Hopes By Drew Armstrong and Robert Langreth Dec 6, 2011 [snip] "Solanezumab is an antibody designed to clear protein fragments called beta amyloid that clutter the brains of patients with Alzheimer’s disease. Pfizer Inc. (PFE), Johnson & Johnson and Elan are testing bapineuzumab, a similar drug." [snip] Read the article

From Drug Discovery & Development : Positive Study Results for Schizophrenia Drug Drug Discovery & Development December 05, 2011 "EnVivo Pharmaceuticals announced the analysis of a completed Phase 2b clinical trial of EVP-6124, a novel, orally bioavailable nicotinic alpha-7 agonist, in schizophrenia." Read the full report

An interesting posting on the Pharmalot blog today: Russian Trial Rules Are A ‘Serious Blow’ To Pharma By Ed Silverman November 29th, 2011 // 9:56 am Read the blog post

Parliamentary Office of Science and Technology POSTNote October 2011 POSTNote: Clinical Trials (pdf).

New pharmacological strategies for treatment of Alzheimer's disease: focus on disease-modifying drugs British Journal of Clinical Pharmacology. 2011 Oct 28; Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F Abstract Current approved drug treatments for Alzheimer disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine. These drugs provide symptomatic relief but poorly affect the progression of the disease. Drug discovery has been directed, in the last ten years, to develop "disease-modifying drugs" hopefully able to counteract the progression of AD. Because in a chronic, slow progressing pathological process, such as AD, an early start of treatment enhances the chance of success, it is crucial to have biomarkers for early detection of AD-related brain dysfunction, usable before clinical onset. Reliable early biomarkers need therefore to be prospectively tested for predictive accuracy, with specifi...

From EurekaAlert: UCSF-Pfizer partnership yields projects aimed at clinical trials 26 October 2011 Read the full article

The current (October 2011) issue of the Canadian Journal of Psychiatry has free-download access to two review articles dealing with Alzheimer's disease. One deals with drug treatment, whilst the other addresses non-pharmacolgic treatments. An editiorial by Serge Gauthier (also a free download) introduces the issue. Canadian Journal of Psychiatry

A report from Fierce BioTech : Third Rock Ventures Launches SAGE Therapeutics to Address CNS Disorders with Critical Unmet Needs Posted October 18, 2011 [snippet] "Third Rock Ventures, LLC today announced the formation of SAGE Therapeutics. The company was launched with a $35 million Series A financing. SAGE's efforts focus on advancing a broad pipeline of new, critically needed treatments for some of the most disabling central nervous system (CNS) disorders such as schizophrenia, depression, pain and traumatic brain injury (TBI). SAGE Therapeutics is founded on a proprietary Positive and Negative Allosteric Modulator (PANAM) chemistry platform that will enable the rapid development of a novel class of allosteric receptor modulators. Steven Paul, M.D., the former executive vice president for science and technology and president of Lilly Research Laboratories and a former scientific director of the National Institute of Mental Health (NIMH) and Douglas Covey, Ph.D., professor o...

The SIST-M: Predictive Validity of a Brief Structured Clinical Dementia Rating Interview Alzheimer Disease and Associated Disorders. 2011 Oct 6; Okereke OI, Pantoja-Galicia N, Copeland M, Hyman BT, Wanggaard T, Albert MS, Betensky RA, Blacker D Abstract BACKGROUND:: We have previously established the reliability and cross-sectional validity of the SIST-M (Structured Interview and Scoring Tool-Massachusetts Alzheimer's Disease Research Center), a shortened version of an instrument shown to predict progression to Alzheimer disease (AD), even among persons with very mild cognitive impairment (vMCI). OBJECTIVE:: To test the predictive validity of the SIST-M. METHODS:: Participants were 342 community-dwelling, nondemented older adults in a longitudinal study. Baseline Clinical Dementia Rating (CDR) ratings were determined by either (1) clinician interviews or (2) a previously developed computer algorithm based on 60 questions (of a possible 131) extracted from clinician interviews. We ...

The Cochrane Collaboration Supports Free Access to all Data from all Clinical Trials 05 October 2011 Read the full statement

A fine read from the Pharmalot blog: All Trial Data Must Be Disclosed: Rogawski Explains By Ed Silverman October 5th, 2011 - 9:36 am Read the full blog posting

Conference Website From the homepage: "Plan now to attend the ACRM-ASNR 2011 Annual Conference at the Hyatt Regency Atlanta. This annual conference draws rehabilitation researchers and clinicians from 20+ countries with a welcoming ambiance suited to seasoned and early career professionals alike. Attendees enjoy exceptional continuing education programs with productive networking opportunities. "Choose from internationally recognized plenary speakers, and symposia covering methodology and technology; practice, policy and reimbursement; neuroscience and neurorehabilitation; and musculoskeletal, aging, and development. "In addition, there are six pre-conference symposia and an Early Career Course on Wednesday. Paper presentations and poster displays, and an exhibition featuring state-of-the-art equipment and services for the rehabilitation professional. As always, there is the opportunity to meet new friends and greet old ones."

Summer School in Applied Psychometrics From the website: Date: Monday, 12 September to Friday, 16 September Location: Peterhouse College, Cambridge Time: All Day Event "Health-related quality of life (HRQoL) is a popular and rapidly evolving area of psychometric research that builds on a long-standing methodology of self-report questionnaires. Today the assessment, analysis and interpretation of these questionnaires and of Patient-Reported Outcomes (PROs) rely upon a variety of modern psychometric methods that might be beyond the typical methodological/statistical training that researcher of related disciplines receive. This Summer School will cover the fundamentals of psychometric test theory as applied to HRQoL and PROs, with particular emphasis on latent trait/ Item Response Theory (IRT) models and methods, and will include practical sessions and data from real-world applications trials and cohort studies. The Summer School is supported by the ESRC RDI (Researcher D...

Investors ready to craft new biotechs out of Pfizer's discards February 9, 2011 — 8:47am ET By John Carroll FierceBiotech Read the article

From The Guardian : Cuts disastrous for brain science research, academics warn At least 30 neuroscience units to go under cuts proposed by Biotechnology and Biological Sciences Research Council Ian Sample guardian.co.uk Thursday 10 February 2011 21.14 GMT [snip] "The closure of drug company research facilities and "draconian" funding cuts will have a disastrous impact on brain science in Britain, senior academics have warned. "At least 30 neuroscience research groups are expected to fold under cuts proposed by the Biotechnology and Biological Sciences Research Council (BBSRC), adding to jobs already lost after big pharmaceutical companies shut research programmes or moved them abroad." [snip] Read the full article

From the FDA (.pdfs of briefing material is available at the link below): January 20-21, 2011: Peripheral and Central Nervous System Drugs Advisory Committee Meeting Announcement Read the full announcement Agenda "On January 20, 2011, the committee will discuss new drug application (NDA) 202-008, florbetapir F 18 injection, sponsored by Avid Radiopharmaceuticals, Inc. , proposed for use in positron emission tomography (PET) imaging of β-amyloid (beta-amyloid) aggregates in the brain to help rule out Alzheimer's disease. "On January 21, 2011, the committee will discuss NDA 201-277, gadobutrol injection, sponsored by Bayer HealthCare Pharmaceuticals, proposed for use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity (abnormal blood supply and circulation) of the central nervous system. The BBB is an area consisting of specialized ...

From The New York Times : Tests Show Promise for Early Diagnosis of Alzheimer’s By GINA KOLATA The New York Times Published: January 18, 2011 "Researchers report major advances on two vexing questions about Alzheimer’s: How do you know if someone who is demented has it? And how can you screen the general population for risk?" Read the full article. The report includes discussion about this week's forthcoming FDA Advisory Committee discussion about Avid Radiopharmaceuticals product.