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Dive into the research topics where Natalie Valle Guzman is active.

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Featured researches published by Natalie Valle Guzman.


The Lancet | 2014

Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial

Stéphane Palfi; Jean Marc Gurruchaga; G. Scott Ralph; Helene Lepetit; Sonia Lavisse; Philip C. Buttery; Colin Watts; James Miskin; Michelle Kelleher; Sarah Deeley; Hirokazu Iwamuro; Jean Pascal Lefaucheur; Claire Thiriez; Gilles Fénelon; Cherry Lucas; Pierre Brugières; Inanna Gabriel; Kou Abhay; Xavier Drouot; Naoki Tani; Aurélie Kas; Bijan Ghaleh; Philippe Le Corvoisier; Patrice Dolphin; David P. Breen; Sarah Mason; Natalie Valle Guzman; Nicholas D. Mazarakis; Pippa A. Radcliffe; Richard Harrop

BACKGROUND Parkinsons disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinsons disease. METHODS We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinsons disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×10(7) transducing units [TU]); mid dose (4·0×10(7) TU); and high dose (1×10(8) TU). Inclusion criteria were age 48-65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinsons Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov, NCT00627588 and NCT01856439. FINDINGS 15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on-off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure were reported. A significant improvement in mean UPDRS part III motor scores off medication was recorded in all patients at 6 months (mean score 38 [SD 9] vs 26 [8], n=15, p=0·0001) and 12 months (38 vs 27 [8]; n=15, p=0·0001) compared with baseline. INTERPRETATION ProSavin was safe and well tolerated in patients with advanced Parkinsons disease. Improvement in motor behaviour was observed in all patients. FUNDING Oxford BioMedica.


Movement Disorders | 2014

Tracking motor impairments in the progression of Huntington's disease

Jeffery D. Long; Jane S. Paulsen; Karen Marder; Ying Zhang; Ji In Kim; James A. Mills; Stephen Cross; Patricia Ryan; Eric A. Epping; Stacie Vik; Edmond Chiu; Joy Preston; Anita Goh; Stephanie Antonopoulos; Samantha Loi; Phyllis Chua; Angela Komiti; Lynn A. Raymond; Joji Decolongon; Mannie Fan; Allison Coleman; Christopher Ross; Mark Varvaris; Nadine Yoritomo; William M. Mallonee; Greg Suter; Ali Samii; Alma Macaraeg; Randi Jones; Cathy Wood-Siverio

The Unified Huntingtons Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene‐expanded participants from the Neurobiological Predictors of Huntingtons Disease (PREDICT‐HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntingtons disease research and the planning of clinical trials of efficacy are discussed.


Neuropsychologia | 2015

The role of the amygdala during emotional processing in Huntington's disease : from pre-manifest to late stage disease

Sarah Mason; Jiaxiang Zhang; Faye Begeti; Natalie Valle Guzman; Alpar Alexandru Lazar; James B. Rowe; Roger A. Barker; Adam Hampshire

Background Deficits in emotional processing can be detected in the pre-manifest stage of Huntingtons disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. Methods We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntingtons disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: “the Reading the Mind in the Eyes Test” which has been previously been shown to be amygdala dependent. Results Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, p<0.05). Furthermore, performance on the “Reading the Mind in the Eyes Test” correlated negatively with proximity to disease onset and became progressively worse with each stage of disease. Conclusion Abnormalities in the neural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntingtons disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis. Furthermore, the “Reading the Mind in the Eyes Test” is a surrogate measure of amygdala function that is clinically useful across the entire cross-section of disease stages in HD.


Journal of Neurology | 2013

The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease

Faye Begeti; Adrian Y. K. Tan; Gemma Cummins; Lucy M Collins; Natalie Valle Guzman; Sarah Mason; Roger A. Barker

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington’s disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke’s Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington’s disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington’s disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington’s disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington’s disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington’s disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.


Journal of Parkinson's disease | 2014

Which patients with Parkinson's disease participate in clinical trials?: One centre's experiences with a new cell based therapy trial (TRANSEURO)

Sarah F. Moore; Natalie Valle Guzman; Sarah Mason; Caroline H. Williams-Gray; Roger A. Barker

BACKGROUND There is currently little evidence regarding the selection of patients for clinical trials in Parkinsons Disease (PD), especially those involving experimental therapies delivered using invasive techniques. OBJECTIVE Understanding which patients are recruited will increase awareness of issues regarding parity of access to clinical trials and have an impact on the wider applicability of results, as well as provoking discussion regarding future improvements in the enrolment process. METHODS TRANSEURO is an open label multi-centre surgical transplant trial which seeks to investigate the feasibility and efficacy of grafts of human foetal ventral mesencephalic tissue in patients with PD. The Cambridge based cohort of TRANSEURO participants (n = 26) was compared with a population representative sample of patients with PD eligible for, but not enrolled in, TRANSEURO (n = 33). Measurements were available in both populations for demographics, neuropsychological tests, tests of motor and non-motor function and quality of life. RESULTS Patients enrolled in TRANSEURO were younger and had significantly more years of education with higher scores on the revised Addenbrookes Cognitive Examination. This difference was accounted for by memory, fluency and visuospatial subscores. There were significant differences in the Movement Disorder Society Unified PD Rating Scale scores with better motor function but more motor complications in the enrolled group. Those enrolled were also more likely to be under the care of the principal investigator of the study. CONCLUSIONS In this trial our population was younger and more educated with higher cognitive scores and better motor function than eligible PD patients not enrolled. This raises interesting questions about the parity of access to clinical trials of this nature amongst patients with PD.


npj Parkinson's disease | 2017

Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson’s disease

Rashmi Lakshminarayana; Duolao Wang; David J. Burn; K. Ray Chaudhuri; Clare Galtrey; Natalie Valle Guzman; Bruce Hellman; Ben James; Suvankar Pal; Jon Stamford; Malcolm Steiger; Rw Stott; James Teo; Roger A. Barker; Emma Yu Wang; Bastiaan R. Bloem; Martijn van der Eijk; Lynn Rochester; Adrian Williams

The progressive nature of Parkinson’s disease, its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge. Clinicians have limited face-to-face consultation time with Parkinson’s disease patients, making it difficult to comprehensively address non-adherence. Here we share the results from a multi-centre (seven centres) randomised controlled trial conducted in England and Scotland to assess the impact of using a smartphone-based Parkinson’s tracker app to promote patient self-management, enhance treatment adherence and quality of clinical consultation. Eligible Parkinson’s disease patients were randomised using a 1:1 ratio according to a computer-generated random sequence, stratified by centre and using blocks of variable size, to intervention Parkinson’s Tracker App or control (Treatment as Usual). Primary outcome was the self-reported score of adherence to treatment (Morisky medication adherence scale −8) at 16 weeks. Secondary outcomes were Quality of Life (Parkinson’s disease questionnaire −39), quality of consultation for Parkinson’s disease patients (Patient-centred questionnaire for Parkinson’s disease), impact on non-motor symptoms (Non-motor symptoms questionnaire), depression and anxiety (Hospital anxiety and depression scale) and beliefs about medication (Beliefs about Medication Questionnaire) at 16 weeks. Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate. 158 patients completed the study (Parkinson’s tracker app = 68 and TAU = 90). At 16 weeks Parkinson’s tracker app significantly improved adherence, compared to treatment as usual (mean difference: 0.39, 95%CI 0.04–0.74; p = 0.0304) with no confounding effects of gender, number of comorbidities and age. Among secondary outcomes, Parkinson’s tracker app significantly improved patients’ perception of quality of consultation (0.15, 95% CI 0.03 to 0.27; p = 0.0110). The change in non-motor symptoms was −0.82 (95% CI −1.75 to 0.10; p = 0.0822). 72% of participants in the Parkinson’s tracker app group continued to use and engage with the application throughout the 16-week trial period. The Parkinson’s tracker app can be an effective and novel way of enhancing self-reported medication adherence and quality of clinical consultation by supporting self-management in Parkinson’s disease in patients owning smartphones. Further work is recommended to determine whether the benefits of the intervention are maintained beyond the 16 week study period.Digital healthcare: App helps patients stick to planA smartphone-based application improves treatment adherence of patients with Parkinson’s disease (PD). Rashmi Lakshminarayana, from uMotif Ltd, and researchers from the UK and The Netherlands describe the results of a 16 week trial of a Parkinson’s tracker app (PTA) that randomised 215 patients from seven different health centres. Patients using the app reported significantly better adherence to their medication plan compared with control patients who continued their treatment as usual. Interestingly, using the PTA also improved the patients’ perception of the quality of their clinical care, possibly as a result of feeling more involved and in control of their care. These findings suggest that by sending medication reminders and tracking symptoms, the app can help patients with Parkinson’s self-manage their increasingly complex treatment regimen as the disease progresses.


npj Parkinson's disease | 2017

Author Correction: Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson’s disease

Rashmi Lakshminarayana; Duolao Wang; David J. Burn; K. Ray Chaudhuri; Clare Galtrey; Natalie Valle Guzman; Bruce Hellman; Ben James; Suvankar Pal; Jon Stamford; Malcolm Steiger; Rw Stott; James Teo; Roger A. Barker; Emma Yu Wang; Bastiaan R. Bloem; Martijn van der Eijk; Lynn Rochester; Adrian Williams

In the original version of this article the copyright notice was missing from Tables 1 and 3. This has now been added alongside the three relevant references inserted as refs. 21–23. The correction has been published and is appended to both the HTML and PDF versions of this paper. The errors have been fixed in the paper.

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Sarah Mason

University of Cambridge

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Adrian Williams

University Hospitals Birmingham NHS Foundation Trust

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Duolao Wang

Liverpool School of Tropical Medicine

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Emma Yu Wang

Queen Mary University of London

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Faye Begeti

University of Cambridge

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James Teo

University of Cambridge

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Rashmi Lakshminarayana

Centre for Economic Performance

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