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BOSTON--(BUSINESS WIRE)--Karuna Pharmaceuticals, focused on targeting muscarinic receptors for the treatment of central nervous system (CNS) disorders including schizophrenia and Alzheimer’s Disease and a subsidiary of PureTech Health (LSE: PRTC), today announced that it will present additional data from the KarXT tolerability proof-of-concept study at two upcoming major medical meetings - The Society of Biological Psychiatry's (SOBP) 72nd Annual Scientific Program and Convention and The American Society of Clinical Psychopharmacology (ASCP) Annual Meeting. The additional data will be presented by newly appointed Karuna Chief Medical Officer (CMO) and former Vice President and head of Neuroscience at Takeda, Stephen Brannan, M.D. and Karuna Chief Clinical Advisor and former Chief Medical Officer at Eli Lilly, Alan Breier, M.D. The Society of Biological Psychiatry's 72nd Annual Scientific Program and Convention in San Diego, California The American Society of Clinical Psychopharmacology Annual Meeting in Miami, Florida The presentations build on topline data from the KarXT tolerability proof-of-concept study, which were announced in December 2016 and provide a clear proof-of-concept that the KarXT approach improves the tolerability of xanomeline. In this study, KarXT was shown to reduce the incidence of prespecified cholinergic adverse events by a statistically significant and clinically meaningful extent (46%, p=0.016) compared to xanomeline alone and each individual cholinergic adverse event was reported at a lower rate in the KarXT treatment arm. The cholinergic adverse event rate was also similar to placebo during the lead-in period. No severe or serious adverse events were reported. KarXT combines xanomeline, a novel clinical-stage muscarinic acetylcholine receptor agonist, with trospium chloride, a muscarinic antagonist, and is being developed to selectively target muscarinic receptors in the CNS. Exclusively licensed to Karuna, xanomeline has demonstrated robust efficacy in reducing psychosis in both schizophrenia and Alzheimer’s disease in previous studies; however, it has been associated with side effects that have limited its development. “We’re excited to reveal additional data that support the enhanced tolerability of our proprietary KarXT approach,” said Andrew Miller, Ph.D., Chief Executive Officer of Karuna. “We’re also thrilled to welcome Steve as CMO to lead our clinical development and medical affairs efforts as we prepare to advance KarXT to a Phase 2 clinical trial this year. Steve’s impressive experience in drug development, his expertise in neuropsychiatric research, and his dedication to finding new treatments will be great assets to Karuna as we continue to work towards developing the first truly novel antipsychotic agent for patients with schizophrenia or Alzheimer’s in more than sixty years.” Dr. Brannan will lead the presentations at the ASCP Annual Meeting. In his new position as CMO, Dr. Brannan will oversee clinical development and medical affairs across Karuna’s innovative therapies for the treatment of psychosis and cognitive dysfunction across CNS disorders including schizophrenia and Alzheimer’s Disease. Dr. Brannan has extensive industry experience, having served as the Vice President and Head of Neuroscience at Takeda in addition to senior positions within Novartis, Eli Lilly, Forum Pharmaceuticals, and Cyberonics. He has been active in the development of important central nervous system treatments including Cymbalta, Exelon Patch, Trintellix, and VNS for Treatment Resistant Depression. Prior to working in the pharmaceutical industry, Dr. Brannan was part of the faculty at the University of Texas Health Science Center at San Antonio (UTHSCSA) where he specialized in Mood and Anxiety disorders. Dr. Brannan has over 40 publications and routinely gives invited talks and presentations at industry conferences. Dr. Brannan trained in psychiatry at UTHSCSA and holds a M.D. degree from the University of Texas Southwestern Medical School. “I’m excited to join Karuna and to have the opportunity to have a key role in developing this exciting, novel approach to treating patients with psychosis and cognitive impairment,” said Dr. Brannan. “These disorders impact millions of people who have significant unmet needs for new and better treatments to adequately and safely manage their symptoms.” About Karuna Karuna is a clinical-stage drug development company targeting muscarinic receptors for the treatment of central nervous system (CNS) disorders. Karuna's lead program, KarXT, is a product candidate consisting of xanomeline, a novel muscarinic acetylcholine receptor agonist that has demonstrated efficacy in placebo-controlled human trials in schizophrenia and Alzheimer’s disease, and trospium chloride, an FDA-approved and well-established muscarinic receptor antagonist that has been shown not to enter the CNS. Karuna intends to evaluate KarXT in a Phase 2 trial set to begin in 2017. Karuna’s Board of Directors includes Ben Shapiro, M.D., PureTech Health Non-Executive Director & former Executive Vice President of Research for Merck; Edmund Harrigan, M.D., former Senior Vice President for Worldwide Safety and Regulatory, Head of Worldwide Business Development at Pfizer; and Atul Pande, M.D., PureTech Health Chief Medical Officer & Former Senior Vice President, Head of Neuroscience and Senior Advisor, Pharmaceutical R&D at GlaxoSmithKline. Karuna’s Chief Clinical Advisor is Alan Breier, M.D., the former Chief Medical Officer at Eli Lilly. Karuna, co-founded by PureTech Health, has a worldwide exclusive license for xanomeline and has a patent portfolio more broadly covering selective muscarinic targeting enabled by the KarXT approach. For more information, visit www.karunapharma.com. Forward Looking Statement This press release contains statements that are or may be forward-looking statements, including statements that relate to the company's future prospects, developments and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks and uncertainties that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks and uncertainties described in the risk factors included in the regulatory filings for PureTech Health plc. These forward-looking statements are based on assumptions regarding the present and future business strategies of the company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, neither the company nor any other party intends to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.

Cai H.,Central South University | Dong L.Q.,UTHSCSA | Liu F.,Central South University
Trends in Pharmacological Sciences | Year: 2016

The increasing epidemic of obesity and its comorbidities has spurred research interest in adipose biology and its regulatory functions. Recent studies have revealed that the mechanistic target of rapamycin (mTOR) signaling pathway has a critical role in the regulation of adipose tissue function, including adipogenesis, lipid metabolism, thermogenesis, and adipokine synthesis and/or secretion. Given the importance of mTOR signaling in controlling energy homeostasis, it is not unexpected that deregulated mTOR signaling is associated with obesity and related metabolic disorders. In this review, we highlight current advances in understanding the roles of the mTOR signaling pathway in adipose tissue. We also provide a more nuanced view of how the mTOR signaling pathway regulates adipose tissue biology and function. Finally, we describe approaches to modulate the activity and tissue-specific function of mTOR that may pave the way towards counteracting obesity and related metabolic diseases. © 2015 Elsevier Ltd. All rights reserved.

Dobie R.A.,UTHSCSA | Dobie R.A.,University of California at Davis | Agrawal Y.,Johns Hopkins University
Audiology and Neurotology | Year: 2011

One can study occupational noise exposure by comparing hearing thresholds of exposed people to control data from national or international standards. ANSI S3.44 (1996) offers Annex C - thresholds for people without occupational noise exposure - as appropriate control data for such comparisons. Annex C is based on the false assumption that people who have had occupational noise exposure are similar in all other important ways to those without such exposures. In fact, people with noisy jobs are more likely than others to be smokers, diabetics, poorly educated, white and exposed to non-occupational noise. Taking these other risk factors into account, the appropriate thresholds for comparison to industrial study populations are closer to those of the unscreened population than to an 'Annex C' population that simply excludes occupationally noise-exposed persons. Copyright © 2010 S. Karger AG, Basel.

News Article | February 15, 2017
Site: www.prweb.com

Amber Hills Dental is set to open its doors on February 6, 2017. The Henderson dental practice aims to provide a comfortable and convenient dental experience for the entire family. Dr. Aimee Villamayor leads the practice as a skilled dentist who carries training and experience throughout a wide range of dental specialties. Patients can take advantage of general and restorative dentistry as well as cosmetic dentistry and orthodontics. Beginning from a first dental visit at six months old to getting dental implants as a senior adult, Amber Hills Dental is uniquely qualified to meet oral health needs through all stages of life. Patient comfort is deeply valued at Amber Hills Dental. They have designed their office environment to include patient amenities, such as Netflix, a beverage bar, children’s play area and video games. The entire practice is centered around taking the stress and anxiety out of dental care. This also includes easy financing options, family block appointments and same day dentistry. Amber Hills will be offering the latest and most preferred dental treatments available, ranging from Invisalign clear orthodontics to implant overdentures. Dr. Villamayor also treats children with a full menu of pediatric dental services, including stainless steel crowns and emergency dental care. “Our team shares a passion to deliver the best possible dental care to the Henderson community. I believe we’ve equipped our practice to do just that. We look forward to welcoming new patients in February,” says Dr. Villamayor of Amber Hills Dental. Dr. Aimee Villamayor received her Bachelor of Science in Biology from the University of San Francisco (USF) and earned her dental degree at New York University College of Dentistry (NYUCD). She is an advocate for continuous learning and completed one year of advanced general dentistry residency at the University of Texas, San Antonio (UTHSCSA). Dr. Villamayor participated in extensive training in dental implants, oral surgeries and dental IV/ oral sedation. Her experience has equipped her to handle dental emergencies and treat medically complex patients. Dr. Villamayor is an active member of the Academy of General Dentistry, American Dental Association and Southern Nevada Dental Association. For more information about the practice or to schedule an appointment at Amber Hills Dental, please visit amberhillsdental.com or call the Henderson office directly at (702) 830-7793.

Schwartz S.,University of Pennsylvania | Defronzo R.A.,UTHSCSA
Current Diabetes Reports | Year: 2014

Patients with hyperglycemia in hospital have increased adverse outcomes compared with patients with normoglycemia, and the pathophysiological causes seem relatively well understood. Thus, a rationale for excellent glycemic control exists. Benefits of control with intensive insulin regimes are highly likely based on multiple published studies. However, hypoglycemia frequency increases and adverse outcomes of hypoglycemia accrue. This has resulted in a 'push' for therapeutic nihilism, accepting higher glycemic levels to avoid hypoglycemia. One would ideally prefer to optimize glycemia, treating hyperglycemia while minimizing or avoiding hypoglycemia. Thus, one would welcome therapies and processes of care to optimize this benefit/ risk ratio. We review the logic and early studies that suggest that incretin therapy use in-hospital can achieve this ideal. We strongly urge randomized prospective controlled studies to test our proposal and we offer a process of care to facilitate this research and their use in our hospitalized patients. © 2014 Springer Science+Business Media New York.

Seillier A.,UTHSCSA | Advani T.,UTHSCSA | Cassano T.,University of Foggia | Hensler J.G.,UTHSCSA | Giuffrida A.,UTHSCSA
International Journal of Neuropsychopharmacology | Year: 2010

The cannabinoid hypothesis of schizophrenia tulates that over-activity of the endocannabinoid system might contribute to the aetiology of schizophrenia. In keeping with this hypothesis, increased expression of CB1 receptors, elevation of the endocannabinoid anandamide (AEA) and cannabinoid-induced cognitive changes have been reported in animal models of schizophrenia and psychotic patients. In this study we measured brain endocannabinoid levels and [35S]GTPS binding stimulated by the CB receptor agonist CP55,940 in rats undergoing withdrawal from subchronic administration of phencyclidine (PCP), a well-established pharmacological model of schizophrenia. We also investigated whether systemic application of the fatty-acid amide hydrolase (FAAH) inhibitor URB597 or CB1 receptor blockade by AM251 affected the following PCP-induced behavioural deficits reminiscent of schizophrenia-like symptoms: (1) working-memory impairment (cognitive deficit), (2) social withdrawal (negative symptom), and (3) hyperactivity in response to d-amphetamine challenge (positive symptoms). PCP-treated rats showed increased endocannabinoid levels in the nucleus accumbens and ventral tegmental area, whereas CB1 receptor expression and CP55,940-stimulated [35S]GTPS binding were unaltered. URB597 reversed the PCP-induced social withdrawal but caused social withdrawal and working-memory deficits in saline-treated rats that were comparable to those observed after PCP treatment. Administration of AM251 ameliorated the working-memory deficit in PCP-treated rats, but impaired working memory in saline-injected controls. Taken together, these results suggest that FAAH inhibition may improve negative symptoms in PCP-treated rats but produce deleterious effects in untreated animals, possibly by disturbing endocannabinoid tone. A similar pattern (beneficial for schizophrenia-related cognitive deficits, but detrimental under normal conditions) accompanies CB1 receptor blockade. © 2009 CINP.

Velligan D.,UTHSCSA | Mintz J.,UTHSCSA | Maples N.,UTHSCSA | Li X.,UTHSCSA | And 3 more authors.
Schizophrenia Bulletin | Year: 2013

Poor adherence to medication leads to symptom exacerbation and interferes with the recovery process for patients with schizophrenia. Following baseline assessment, 142 patients in medication maintenance at a community mental health center were randomized to one of 3 treatments for 9 months: (1) PharmCAT, supports including pill containers, signs, alarms, checklists and the organization of belongings established in weekly home visits from a PharmCAT therapist; (2) Med-eMonitor (MM), an electronic medication monitor that prompts use of medication, cues the taking of medication, warns patients when they are taking the wrong medication or taking it at the wrong time, record complaints, and, through modem hookup, alerts treatment staff of failures to take medication as prescribed; (3) Treatment as Usual (TAU). All patients received the Med-eMonitor device to record medication adherence. The device was programmed for intervention only in the MM group. Data on symptoms, global functioning, and contact with emergency services and police were obtained every 3 months. Repeated measures analyses of variance for mixed models indicated that adherence to medication was significantly better in both active conditions than in TAU (both p<0.0001). Adherence in active treatments ranged from 90-92% compared to 73% in TAU based on electronic monitoring. In-person and electronic interventions significantly improved adherence to medication, but that did not translate to improved clinical outcomes. Implications for treatment and health care costs are discussed. © The Author 2012. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.

Akopian A.N.,UTHSCSA
Current Pharmaceutical Biotechnology | Year: 2011

TRPV1 and TRPA1 have traditionally been considered to function independently from each other as homomers, but their extensive co-expression in sensory neurons and recent evidence suggest that these channels can functionally interact and may form a complex as part of their normal function. Although TRPA1 and TRPV1 do not absolutely require interaction to maintain function in expression systems or even sensory neurons, their heteromerization may still result in dramatic effects on channel biophysical properties, pharmacology, signaling, regulation, and ultimately function. Understanding the regulation and functional significance of TRPA1-TRPV1 interaction is of tremendous clinical importance since first, both channels are the potential molecular targets for numerous therapeutic drugs; and second, TRPA1-TRPV1 co-expression is far more specific for nociceptive sensory neurons than expression patterns of TRPA1 or TRPV1 considered separately. © 2011 Bentham Science Publishers Ltd.

Mann M.,UTHSCSA | Cortez V.,UTHSCSA | Vadlamudi R.K.,UTHSCSA
Cancers | Year: 2011

Estrogen receptor (ERα) signaling plays a key role in hormonal cancer progression. ERα is a ligand-dependent transcription factor that modulates gene transcription via recruitment to the target gene chromatin. Emerging evidence suggests that ERα signaling has the potential to contribute to epigenetic changes. Estrogen stimulation is shown to induce several histone modifications at the ERα target gene promoters including acetylation, phosphorylation and methylation via dynamic interactions with histone modifying enzymes. Deregulation of enzymes involved in the ERα-mediated epigenetic pathway could play a vital role in ERα driven neoplastic processes. Unlike genetic alterations, epigenetic changes are reversible, and hence offer novel therapeutic opportunities to reverse ERα driven epigenetic changes. In this review, we summarize current knowledge on mechanisms by which ERα signaling potentiates epigenetic changes in cancer cells via histone modifications. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

DeFronzo R.A.,UTHSCSA | Stonehouse A.H.,Amylin Pharmaceuticals Inc. | Han J.,Amylin Pharmaceuticals Inc. | Wintle M.E.,Amylin Pharmaceuticals Inc.
Diabetic Medicine | Year: 2010

Aims: Baseline glycated haemoglobin (HbA1c) concentrations vary between clinical trials of glucose-lowering agents and this may affect interpretation of clinical efficacy. The objective of this study is to quantify the relationship between baseline HbA1c and reduction of HbA 1c in clinical trials. Methods: PubMed literature searches from 1991 to 2007. Randomized controlled studies with placebo-controlled or comparator arms [≥ 9 patients in the intent-to-treat (ITT) population] ranging in duration from 23 to 52 weeks, in which baseline and change in glycated haemoglobin (HbA1c) were reported. The relationship between baseline HbA1c and change in HbA1c was analysed by a weighted least-squared regression model accounting for ITT population and variance of HbA1c change. Fourteen per cent of independently abstracted studies met the selection criteria. Results: Meta-analysis from 59 clinical trials (8479 patients) produced weighted R2 of 0.35 (P < 0.0001) for the association of baseline HbA1c and absolute change in HbA 1c. Subanalysis of eight metformin clinical trials demonstrated a stronger association [weighted R2 of 0.67 (P = 0.0130)]. Exclusion of metformin clinical trials from the overall meta-analysis (n = 51) yielded a weighted R2 of 0.31 (P < 0.0001). Subanalyses of clinical trials of glucose-lowering therapies predominantly targeting fasting (n = 37) or postprandial (n = 22) blood glucose produced weighted R2 values of 0.27 (P < 0.001) and 0.42 (P < 0.005), respectively. Conclusions: These data demonstrate a positive relationship between baseline HbA1c and the magnitude of HbA1c change across 10 categories of glucose-lowering therapies, irrespective of class or mode of action. These observations should be considered when assessing clinical efficacy of diabetes therapies derived from clinical trials. © 2010 The Authors.

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