Publications
112 results found
Quinn K, Bouliotis G, Doyle N, et al., 2016, A first-in-human study, in HIV-positive men, of the novel HIV-fusion inhibitor C34-PEG4-Chol, 22nd Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 18-18, ISSN: 1464-2662
Libri V, Yandim C, Athanasopoulos S, et al., 2014, Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study, The Lancet, Vol: 384, Pages: 504-513, ISSN: 0140-6736
BackgroundFriedreich's ataxia is a progressive degenerative disorder caused by deficiency of the frataxin protein. Expanded GAA repeats within intron 1 of the frataxin (FXN) gene lead to its heterochromatinisation and transcriptional silencing. Preclinical studies have shown that the histone deacetylase inhibitor nicotinamide (vitamin B3) can remodel the pathological heterochromatin and upregulate expression of FXN. We aimed to assess the epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia.MethodsIn this exploratory, open-label, dose-escalation study in the UK, male and female patients (aged 18 years or older) with Friedreich's ataxia were given single doses (phase 1) and repeated daily doses of 2–8 g oral nicotinamide for 5 days (phase 2) and 8 weeks (phase 3). Doses were gradually escalated during phases 1 and 2, with individual maximum tolerated doses used in phase 3. The primary outcome was the upregulation of frataxin expression. We also assessed the safety and tolerability of nicotinamide, used chromatin immunoprecipitation to investigate changes in chromatin structure at the FXN gene locus, and assessed the effect of nicotinamide treatment on clinical scales for ataxia. This study is registered with ClinicalTrials.gov, number NCT01589809.FindingsNicotinamide was generally well tolerated; the main adverse event was nausea, which in most cases was mild, dose-related, and resolved spontaneously or after dose reduction, use of antinausea drugs, or both. Phase 1 showed a dose-response relation for proportional change in frataxin protein concentration from baseline to 8 h post-dose, which increased with increasing dose (p=0·0004). Bayesian analysis predicted that 3·8 g would result in a 1·5-times increase and 7·5 g in a doubling of frataxin protein concentration. Phases 2 and 3 showed that daily dosing at 3·5–6 g resulted in a sustained and significant (p<0&m
Libri V, Gibbs JSR, Pinato DJ, et al., 2014, Capsaicin 8% patch for treprostinil subcutaneous infusion site pain in pulmonary hypertension patients, BRITISH JOURNAL OF ANAESTHESIA, Vol: 112, Pages: 337-347, ISSN: 0007-0912
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- Citations: 2
Owen DR, Guo Q, Kalk NJ, et al., 2014, Eratum: Determination of [ 11 C]PBR28 binding potential in vivo: A first human TSPO blocking study (Journal of Cerebral Blood Flow and Metabolism (2014) 34 (1256)), Journal of Cerebral Blood Flow and Metabolism, Vol: 34, ISSN: 0271-678X
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- Citations: 3
Libri V, 2013, Effects of Capsaicin 8% Patches on SC Treprostinil Infusion Site Pain: Experience from a Randomised Double-Blinded Phase IIa Clinical Trial., 8th John Vane Memorial conference on Prostacyclin Science and Pulmonary Vascular Disease
Owen D, Guo Q, Colasanti A, et al., 2013, Determination of [11C]PBR28 binding potential in vivo: A first human TSPO occupancy study.
Libri V, Brown AP, Gambarota G, et al., 2012, A Pilot Randomized, Placebo Controlled, Double Blind Phase I Trial of the Novel SIRT1 Activator SRT2104 in Elderly Volunteers, PLoS ONE, Vol: 7, ISSN: 1932-6203
Background:SRT2104 has been developed as a selective small molecule activator of SIRT1, a NAD+-dependent deacetylaseinvolved in the regulation of energy homeostasis and the modulation of various metabolic pathways, including glucosemetabolism, oxidative stress and lipid metabolism. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. We report the first clinical trial of SRT2104 in elderlyvolunteers.Methods:Oral doses of 0.5 or 2.0 g SRT2104 or matching placebo were administered once daily for 28 days.Pharmacokinetic samples were collected through 24 hours post-dose on days 1 and 28. Multiple pharmacodynamicendpoints were explored with oral glucose tolerance tests (OGTT), serum lipid profiles, magnetic resonance imaging (MRI)for assessment of whole body visceral and subcutaneous fat, maximal aerobic capacity test and muscle 31P magneticresonance spectroscopy (MRS) for estimation of mitochondrial oxidative capacity.Results:SRT2104 was generally safe and well tolerated. Pharmacokinetic exposure increased less than dose-proportionally.Mean Tmax was 2–4 hours with elimination half-life of 15–20 hours. Serum cholesterol, LDL levels and triglyceridesdecreased with treatment. No significant changes in OGTT responses were observed. 31P MRS showed trends for morerapid calculated adenosine diphosphate (ADP) and phosphocreatine (PCr) recoveries after exercise, consistent withincreased mitochondrial oxidative phosphorylation.Conclusions:SRT2104 can be safely administered in elderly individuals and has biological effects in humans that areconsistent with SIRT1 activation. The results of this study support further development of SRT2104 and may be useful indose selection for future clinical trials in patients.
Pinato DJ, Stavraka C, Tanner M, et al., 2012, Clinical, Ethical and Financial Implications of Incidental Imaging Findings: Experience from a Phase I Trial inHealthy Elderly Volunteers, Plos One, Vol: 7
Stavraka1, Mark Tanner2, Audrey Esson1, Eric W. Jacobson3, Martin R. Wilkins1,Vincenzo Libri1*
Lythe KE, Williams SCR, Anderson C, et al., 2012, Frontal and parietal activity after sleep deprivation is dependent on task difficulty and can be predicted by the fMRI response after normal sleep, BEHAVIOURAL BRAIN RESEARCH, Vol: 233, Pages: 62-70, ISSN: 0166-4328
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- Citations: 45
Libri V, 2010, Developing Products for Rare Diseases: Assessing financial and clinical challenges to navigate the way forward, Evolution Summit 2010
Devanand DP, Mikhno A, Pelton GH, et al., 2010, Pittsburgh compound B (11C-PIB) and fluorodeoxyglucose (18 F-FDG) PET in patients with Alzheimer disease, mild cognitive impairment, and healthy controls, J Geriatr Psychiatry Neurol, Vol: 23, Pages: 185-198, ISSN: 0891-9887
Amyloid load in the brain using Pittsburgh compound B ((11)C-PIB) positron emission tomography (PET) and cerebral glucose metabolism using fluorodeoxyglucose ((18)F-FDG) PET were evaluated in patients with mild Alzheimer disease (AD, n = 18), mild cognitive impairment (MCI, n = 24), and controls (CTR, n = 18). ( 11)C-PIB binding potential (BP(ND)) was higher in prefrontal cortex, cingulate, parietal cortex, and precuneus in AD compared to CTR or MCI and in prefrontal cortex for MCI compared to CTR. For (18)F-FDG, regional cerebral metabolic rate for glucose (rCMRGlu) was decreased in precuneus and parietal cortex in AD compared to CTR and MCI, with no MCI-CTR differences. For the AD-CTR comparison, precuneus BP(ND) area under the receiver operating characteristic (ROC) curve (AUC) was 0.938 and parietal cortex rCMRGlu AUC was 0.915; for the combination, AUC was 0.989. ( 11)C-PIB PET BP(ND) clearly distinguished diagnostic groups and combined with (18)F-FDG PET rCMRGlu, this effect was stronger. These PET techniques provide complementary information in strongly distinguishing diagnostic groups in cross-sectional comparisons that need testing in longitudinal studies.
Libri V, 2010, Experimental medicine endpoints in early-phase clinical trials for CNS indications, Forty Years of Advances in Pharmacology, Editors: Nistico, Rotiroti, De Sarro, Pages: 152-165
Devanand DP, Mikhno A, Pelton GH, et al., 2009, Comparison of Pittsburgh compound B (11C-PIB) and fluorodeoxyglucose (18F-FDG) PET in patients with Alzheimer's disease, mild cognitive impairment, and healthy controls
Thompson PW, Ye L, Morgenstern JL, et al., 2009, Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer’s disease pathologies, Journal of Neurochemistry, Vol: 109, Pages: 623-630
Pan M, Chuah LYM, Chen A, et al., 2008, The neurocognitive effects of donepezil on visual short-term memory capacity following 24 Hours of sleep deprivation, Pages: T507-T508
Pan M, Chuah LYM, Chong D, et al., 2008, The neurocognitive benefits of donepezil on episodic memory in young, healthy individuals following 24 Hours of sleep deprivation, Pages: T506-T507
Mikhno A, Devanand DP, Pelton GH, et al., 2008, Voxel-based analysis of C11 Pittsburgh compound B for diagnosing Alzheimer's disease
Devanand DP, Mikhno A, Pelton GH, et al., 2008, PET amyloid imaging with Pittsburgh Compound B in Alzheimer's disease
Lai RY, Gregory S, Hall D, et al., 2008, A novel potent histamine H3 receptor antagonist produces discrete changes in brain activity during learning and episodic memory: Implications for cognitive enhancement, Pages: T503-T504
Ye L, Velasco A, Fraser G, et al., 2008, In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in post-mortem human brain, Journal of Neurochemistry, Vol: 105, Pages: 1428-1437
Jones N, Messenger MJ, ONeill MJ, et al., 2008, AMPA receptor potentiation can prevent ethanol-induced intoxication, Neuropsychopharmacology, Vol: 33
Mikhno A, Devanand DP, Parsey R, et al., 2008, The use of voxel-based analysis of [11C]PIB scans for the diagnosis of Alzheimer’s disease, Journal of Nuclear Medicine, Vol: 49, Pages: 1262-1269
Lockhart A, Lamb JR, Osredkar T, et al., 2007, PIB is a non-specific imaging marker of amyloid-beta (Aβ) peptide-related cerebral amyloidosis, BRAIN, Vol: 130, Pages: 2607-2615, ISSN: 0006-8950
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- Citations: 250
Lockhart A, Lamb JR, Osredkar T, et al., 2007, Senile plaque type and ApoE genotype affect PIB retention in Alzheimer’s disease, Brain, Vol: 130, Pages: 2607-2615
Jones N, ONeill MJ, Tricklebank M, et al., 2005, Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat brain using pharmacological magnetic resonance imaging, Psychopharmacol., Vol: 180, Pages: 743-751
Skljarevski V, Nitu A, Libri V, et al., 2004, Blink reflex - a review article, J Clin Neurophysiol., Vol: 36, Pages: 244-251
Giffin NJ, Kowacs F, Libri V, et al., 2003, Effect of the adenosine A<sub>1</sub> receptor agonist GR79236 on trigeminal nociception with blink reflex recordings in healthy human subjects, CEPHALALGIA, Vol: 23, Pages: 287-292, ISSN: 0333-1024
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- Citations: 42
Giffin NJ, Kowacs F, Libri V, et al., 2002, Effects of Adenosine A1 receptor agonist GR79236 on trigeminal nociception with blink reflex recordings in healthy human subjects, Cephalalgia, Vol: 21, Pages: 267-272
McCarthy LC, Hosford D, et al, et al., 2001, Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine, Genomics, Vol: 78, Pages: 135-149
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