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News Article | June 12, 2017
Site: globenewswire.com

DUBLIN, Ireland, June 12, 2017 (GLOBE NEWSWIRE) -- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapies, announced today the appointment of Wagner Zago, PhD, as Chief Scientific Officer (CSO). Dr. Zago, who has been Prothena’s Head of Research since 2015, will have responsibility for defining and executing the company’s research strategy and advancing the company’s drug discovery pipeline. "Wagner is a prolific and talented scientist whose expertise has been central to Prothena’s ability to build a diverse pipeline of internally discovered first-in-class therapies,” stated Gene Kinney, PhD, President and Chief Executive Officer of Prothena. “His appointment to the position of CSO reflects our deeply held commitment to our scientific roots and the continued discovery of novel therapies based on our expertise in protein misfolding and cell adhesion. Beyond his exceptional and widely respected scientific talent, Wagner brings tremendous leadership and strategic planning capabilities to our management team that will advance our capacity to develop innovative medicines.” Dr. Zago joined Prothena in 2012 when the company was founded after spinning out of Elan Pharmaceuticals, first as Head of Pharmacology and Neuropathology and more recently as Vice President, Head of Research. During his tenure at Prothena, he has led teams that have built a strong discovery pipeline and advanced four programs based on novel mechanisms through discovery and preclinical development into the clinic. Dr. Zago holds several key patents and has published broadly in the areas of protein immunotherapy and central nervous system (CNS) disorders. Before Prothena, he was Principal Scientist at Elan Pharmaceuticals performing research aimed at developing new therapeutics for CNS disorders, including beta amyloid-targeted therapies and supportive research for the development of natalizumab, which was commercialized by Biogen for relapsing multiple sclerosis. While in this position he also served as a Scientist at Janssen Alzheimer Immunotherapy, where he made significant discoveries about vascular changes associated with anti-beta amyloid immunotherapy. Previously, he was a Postdoctoral Researcher at the University of California – San Diego and the Burnham Institute. Dr. Zago received his PhD in Pharmacology at the Universidade de Sao Paulo, Brazil. Prothena Corporation plc is a global, late-stage clinical biotechnology company establishing fully-integrated research, development and commercial capabilities. Fueled by its deep scientific understanding built over decades of research in protein misfolding and cell adhesion — the root causes of many serious or currently untreatable amyloid and inflammatory diseases — Prothena seeks to fundamentally change the course of progressive diseases associated with this biology. The Company’s pipeline of antibody therapeutic candidates targets a number of indications including AL amyloidosis (NEOD001), Parkinson’s disease and other related synucleinopathies (PRX002/RG7935), inflammatory diseases, including psoriasis and psoriatic arthritis (PRX003), and ATTR amyloidosis (PRX004). The Company continues discovery of additional novel therapeutic candidates where its deep scientific understanding of disease pathology can be leveraged. For more information, please visit the Company’s website at www.prothena.com


News Article | June 12, 2017
Site: globenewswire.com

DUBLIN, Ireland, June 12, 2017 (GLOBE NEWSWIRE) -- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapies, announced today the appointment of Wagner Zago, PhD, as Chief Scientific Officer (CSO). Dr. Zago, who has been Prothena’s Head of Research since 2015, will have responsibility for defining and executing the company’s research strategy and advancing the company’s drug discovery pipeline. "Wagner is a prolific and talented scientist whose expertise has been central to Prothena’s ability to build a diverse pipeline of internally discovered first-in-class therapies,” stated Gene Kinney, PhD, President and Chief Executive Officer of Prothena. “His appointment to the position of CSO reflects our deeply held commitment to our scientific roots and the continued discovery of novel therapies based on our expertise in protein misfolding and cell adhesion. Beyond his exceptional and widely respected scientific talent, Wagner brings tremendous leadership and strategic planning capabilities to our management team that will advance our capacity to develop innovative medicines.” Dr. Zago joined Prothena in 2012 when the company was founded after spinning out of Elan Pharmaceuticals, first as Head of Pharmacology and Neuropathology and more recently as Vice President, Head of Research. During his tenure at Prothena, he has led teams that have built a strong discovery pipeline and advanced four programs based on novel mechanisms through discovery and preclinical development into the clinic. Dr. Zago holds several key patents and has published broadly in the areas of protein immunotherapy and central nervous system (CNS) disorders. Before Prothena, he was Principal Scientist at Elan Pharmaceuticals performing research aimed at developing new therapeutics for CNS disorders, including beta amyloid-targeted therapies and supportive research for the development of natalizumab, which was commercialized by Biogen for relapsing multiple sclerosis. While in this position he also served as a Scientist at Janssen Alzheimer Immunotherapy, where he made significant discoveries about vascular changes associated with anti-beta amyloid immunotherapy. Previously, he was a Postdoctoral Researcher at the University of California – San Diego and the Burnham Institute. Dr. Zago received his PhD in Pharmacology at the Universidade de Sao Paulo, Brazil. Prothena Corporation plc is a global, late-stage clinical biotechnology company establishing fully-integrated research, development and commercial capabilities. Fueled by its deep scientific understanding built over decades of research in protein misfolding and cell adhesion — the root causes of many serious or currently untreatable amyloid and inflammatory diseases — Prothena seeks to fundamentally change the course of progressive diseases associated with this biology. The Company’s pipeline of antibody therapeutic candidates targets a number of indications including AL amyloidosis (NEOD001), Parkinson’s disease and other related synucleinopathies (PRX002/RG7935), inflammatory diseases, including psoriasis and psoriatic arthritis (PRX003), and ATTR amyloidosis (PRX004). The Company continues discovery of additional novel therapeutic candidates where its deep scientific understanding of disease pathology can be leveraged. For more information, please visit the Company’s website at www.prothena.com


News Article | June 12, 2017
Site: globenewswire.com

DUBLIN, Ireland, June 12, 2017 (GLOBE NEWSWIRE) -- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapies, announced today the appointment of Wagner Zago, PhD, as Chief Scientific Officer (CSO). Dr. Zago, who has been Prothena’s Head of Research since 2015, will have responsibility for defining and executing the company’s research strategy and advancing the company’s drug discovery pipeline. "Wagner is a prolific and talented scientist whose expertise has been central to Prothena’s ability to build a diverse pipeline of internally discovered first-in-class therapies,” stated Gene Kinney, PhD, President and Chief Executive Officer of Prothena. “His appointment to the position of CSO reflects our deeply held commitment to our scientific roots and the continued discovery of novel therapies based on our expertise in protein misfolding and cell adhesion. Beyond his exceptional and widely respected scientific talent, Wagner brings tremendous leadership and strategic planning capabilities to our management team that will advance our capacity to develop innovative medicines.” Dr. Zago joined Prothena in 2012 when the company was founded after spinning out of Elan Pharmaceuticals, first as Head of Pharmacology and Neuropathology and more recently as Vice President, Head of Research. During his tenure at Prothena, he has led teams that have built a strong discovery pipeline and advanced four programs based on novel mechanisms through discovery and preclinical development into the clinic. Dr. Zago holds several key patents and has published broadly in the areas of protein immunotherapy and central nervous system (CNS) disorders. Before Prothena, he was Principal Scientist at Elan Pharmaceuticals performing research aimed at developing new therapeutics for CNS disorders, including beta amyloid-targeted therapies and supportive research for the development of natalizumab, which was commercialized by Biogen for relapsing multiple sclerosis. While in this position he also served as a Scientist at Janssen Alzheimer Immunotherapy, where he made significant discoveries about vascular changes associated with anti-beta amyloid immunotherapy. Previously, he was a Postdoctoral Researcher at the University of California – San Diego and the Burnham Institute. Dr. Zago received his PhD in Pharmacology at the Universidade de Sao Paulo, Brazil. Prothena Corporation plc is a global, late-stage clinical biotechnology company establishing fully-integrated research, development and commercial capabilities. Fueled by its deep scientific understanding built over decades of research in protein misfolding and cell adhesion — the root causes of many serious or currently untreatable amyloid and inflammatory diseases — Prothena seeks to fundamentally change the course of progressive diseases associated with this biology. The Company’s pipeline of antibody therapeutic candidates targets a number of indications including AL amyloidosis (NEOD001), Parkinson’s disease and other related synucleinopathies (PRX002/RG7935), inflammatory diseases, including psoriasis and psoriatic arthritis (PRX003), and ATTR amyloidosis (PRX004). The Company continues discovery of additional novel therapeutic candidates where its deep scientific understanding of disease pathology can be leveraged. For more information, please visit the Company’s website at www.prothena.com


News Article | June 12, 2017
Site: globenewswire.com

DUBLIN, Ireland, June 12, 2017 (GLOBE NEWSWIRE) -- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapies, announced today the appointment of Wagner Zago, PhD, as Chief Scientific Officer (CSO). Dr. Zago, who has been Prothena’s Head of Research since 2015, will have responsibility for defining and executing the company’s research strategy and advancing the company’s drug discovery pipeline. "Wagner is a prolific and talented scientist whose expertise has been central to Prothena’s ability to build a diverse pipeline of internally discovered first-in-class therapies,” stated Gene Kinney, PhD, President and Chief Executive Officer of Prothena. “His appointment to the position of CSO reflects our deeply held commitment to our scientific roots and the continued discovery of novel therapies based on our expertise in protein misfolding and cell adhesion. Beyond his exceptional and widely respected scientific talent, Wagner brings tremendous leadership and strategic planning capabilities to our management team that will advance our capacity to develop innovative medicines.” Dr. Zago joined Prothena in 2012 when the company was founded after spinning out of Elan Pharmaceuticals, first as Head of Pharmacology and Neuropathology and more recently as Vice President, Head of Research. During his tenure at Prothena, he has led teams that have built a strong discovery pipeline and advanced four programs based on novel mechanisms through discovery and preclinical development into the clinic. Dr. Zago holds several key patents and has published broadly in the areas of protein immunotherapy and central nervous system (CNS) disorders. Before Prothena, he was Principal Scientist at Elan Pharmaceuticals performing research aimed at developing new therapeutics for CNS disorders, including beta amyloid-targeted therapies and supportive research for the development of natalizumab, which was commercialized by Biogen for relapsing multiple sclerosis. While in this position he also served as a Scientist at Janssen Alzheimer Immunotherapy, where he made significant discoveries about vascular changes associated with anti-beta amyloid immunotherapy. Previously, he was a Postdoctoral Researcher at the University of California – San Diego and the Burnham Institute. Dr. Zago received his PhD in Pharmacology at the Universidade de Sao Paulo, Brazil. Prothena Corporation plc is a global, late-stage clinical biotechnology company establishing fully-integrated research, development and commercial capabilities. Fueled by its deep scientific understanding built over decades of research in protein misfolding and cell adhesion — the root causes of many serious or currently untreatable amyloid and inflammatory diseases — Prothena seeks to fundamentally change the course of progressive diseases associated with this biology. The Company’s pipeline of antibody therapeutic candidates targets a number of indications including AL amyloidosis (NEOD001), Parkinson’s disease and other related synucleinopathies (PRX002/RG7935), inflammatory diseases, including psoriasis and psoriatic arthritis (PRX003), and ATTR amyloidosis (PRX004). The Company continues discovery of additional novel therapeutic candidates where its deep scientific understanding of disease pathology can be leveraged. For more information, please visit the Company’s website at www.prothena.com


Ho C.-Y.,Neuropathology and | Whitehead M.T.,Neuroradiology | Kao A.,Childrens National Health System | Depositario-Cabacar D.,Childrens National Health System | Gaillard W.D.,Childrens National Health System
Journal of neurosurgery. Pediatrics | Year: 2017

OBJECTIVE Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy that often may be treated by surgery. Following resection, many patients continue to experience seizures, necessitating a decision for further surgery to achieve the desired seizure outcomes. Few studies exist on the efficacy of reoperation for intractable epilepsy due to FCD in pediatric cohorts, including the definition of prognostic factors correlated with clinical benefit from further resection. METHODS The authors retrospectively analyzed the medical records and MR images of 22 consecutive pediatric patients who underwent repeat FCD resection after unsuccessful first surgery at the Children's National Health System between March 2005 and April 2015. RESULTS Accounting for all reoperations, 13 (59%) of the 22 patients achieved complete seizure freedom and another 5 patients (23%) achieved significant improvement in seizure control. Univariate analysis demonstrated that concordance in electrocorticography (ECoG) and MRI localization (p = 0.005), and completeness of resection (p = 0.0001), were associated with seizure freedom after the first reoperation. Patients with discordant ECoG and MRI findings ultimately benefited from aggressive multilobe lobectomy or hemispherectomy. Repeat lesionectomies utilizing intraoperative MRI (iMRI; n = 9) achieved complete resection and seizure freedom in all cases. CONCLUSIONS Reoperation may be clinically beneficial in patients with intractable epilepsy due to FCD. Patients with concordant intraoperative ECoG and MRI localization may benefit from extended resection of residual dysplasia at the margins of the previous lesional cavity, and iMRI may offer benefits as a quality control mechanism to ensure that a complete resection has been accomplished. Patients with discordant findings may benefit from more aggressive resections at earlier stages to achieve better seizure control and ensure functional plasticity.


PubMed | Neuropathology and., Neurology., Sainte Anne Hospital, Neuroradiology. and Leeds General Infirmary
Type: Journal Article | Journal: Journal of neurosurgery | Year: 2016

OBJECTIVE There are no guidelines for the management of postoperative lateral sinus thrombosis following posterior fossa surgery. Introducing treatment-dose anticoagulant therapy during the immediate postoperative period increases the risk of intracranial bleeding. This study assessed the incidence of and risk factors associated with postoperative lateral sinus thrombosis and the complications related to thrombosis and/or anticoagulation. METHODS This study was a retrospective monocentric analysis of adult patients who underwent surgical removal of a posterior fossa space-occupying lesion with available postoperative imaging. Postoperative lateral sinus thrombosis was defined as a T2


PubMed | Neuropathology and., Neuroradiology. and Childrens National Medical Center
Type: Journal Article | Journal: Journal of neurosurgery. Pediatrics | Year: 2016

OBJECTIVE Previous meta-analysis has demonstrated that the most important factor in seizure freedom following surgery for focal cortical dysplasia (FCD) is completeness of resection. However, intraoperative detection of epileptogenic dysplastic cortical tissue remains a challenge, potentially leading to a partial resection and the need for reoperation. The objective of this study was to determine the role of intraoperative MRI (iMRI) in the intraoperative detection and localization of FCD as well as its impact on surgical decision making, completeness of resection, and seizure control outcomes. METHODS The authors retrospectively reviewed the medical records of pediatric patients who underwent iMRI-assisted resection of FCD at the Childrens National Health System between January 2014 and April 2015. Data reviewed included demographics, length of surgery, details of iMRI acquisition, postoperative seizure freedom, and complications. Postsurgical seizure outcome was assessed utilizing the Engel Epilepsy Surgery Outcome Scale. RESULTS Twelve consecutive pediatric patients (8 females and 4 males) underwent iMRI-guided resection of FCD lesions. The mean age at the time of surgery was 8.8 years 1.6 years (range 0.7 to 18.8 years), and the mean duration of follow up was 3.5 months 1.0 month. The mean age at seizure onset was 2.8 years 1.0 year (range birth to 9.0 years). Two patients had Type 1 FCD, 5 patients had Type 2A FCD, 2 patients had Type 2B FCD, and 3 patients had FCD of undetermined classification. iMRI findings impacted intraoperative surgical decision making in 5 (42%) of the 12 patients, who then underwent further exploration of the resection cavity. At the time of the last postoperative follow-up, 11 (92%) of the 12 patients were seizure free (Engel Class I). No patients underwent reoperation following iMRI-guided surgery. CONCLUSIONS iMRI-guided resection of FCD in pediatric patients precluded the need for repeat surgery. Furthermore, it resulted in the achievement of complete resection in all the patients, leading to a high rate of postoperative seizure freedom.


PubMed | Neuropathology and., University of Marburg and University Hospital Erlangen
Type: Journal Article | Journal: Neurosurgical focus | Year: 2016

Intraoperative overestimation of resection volume in epilepsy surgery is a well-known problem that can lead to an unfavorable seizure outcome. Intraoperative MRI (iMRI) combined with neuronavigation may help surgeons avoid this pitfall and facilitate visualization and targeting of sometimes ill-defined heterogeneous lesions or epileptogenic zones and may increase the number of complete resections and improve seizure outcome.To investigate this hypothesis, the authors conducted a retrospective clinical study of consecutive surgical procedures performed during a 10-year period for epilepsy in which they used neuronavigation combined with iMRI and functional imaging (functional MRI for speech and motor areas; diffusion tensor imaging for pyramidal, speech, and visual tracts; and magnetoencephalography and electrocorticography for spike detection). Altogether, there were 415 patients (192 female and 223 male, mean age 37.2 years; 41% left-sided lesions and 84.9% temporal epileptogenic zones). The mean preoperative duration of epilepsy was 17.5 years. The most common epilepsy-associated pathologies included hippocampal sclerosis (n = 146 [35.2%]), long-term epilepsy-associated tumor (LEAT) (n = 67 [16.1%]), cavernoma (n = 45 [10.8%]), focal cortical dysplasia (n = 31 [7.5%]), and epilepsy caused by scar tissue (n = 23 [5.5%]).In 11.8% (n = 49) of the surgeries, an intraoperative second-look surgery (SLS) after incomplete resection verified by iMRI had to be performed. Of those incomplete resections, LEATs were involved most often (40.8% of intraoperative SLSs, 29.9% of patients with LEAT). In addition, 37.5% (6 of 16) of patients in the diffuse glioma group and 12.9% of the patients with focal cortical dysplasia underwent an SLS. Moreover, iMRI provided additional advantages during implantation of grid, strip, and depth electrodes and enabled intraoperative correction of electrode position in 13.0% (3 of 23) of the cases. Altogether, an excellent seizure outcome (Engel Class I) was found in 72.7% of the patients during a mean follow-up of 36 months (range 3 months to 10.8 years). The greatest likelihood of an Engel Class I outcome was found in patients with cavernoma (83.7%), hippocampal sclerosis (78.8%), and LEAT (75.8%). Operative revisions that resulted from infection occurred in 0.3% of the patients, from hematomas in 1.6%, and from hydrocephalus in 0.8%. Severe visual field defects were found in 5.2% of the patients, aphasia in 5.7%, and hemiparesis in 2.7%, and the total mortality rate was 0%.Neuronavigation combined with iMRI was beneficial during surgical procedures for epilepsy and led to favorable seizure outcome with few specific complications. A significantly higher resection volume associated with a higher chance of favorable seizure outcome was found, especially in lesional epilepsy involving LEAT or diffuse glioma.


PubMed | Neuropathology and., Neuroradiology. and Childrens National Medical Center
Type: Case Reports | Journal: Neurosurgical focus | Year: 2016

Previous studies have demonstrated that an important factor in seizure freedom following surgery for lesional epilepsy in the peri-eloquent cortex is completeness of resection. However, aggressive resection of epileptic tissue localized to this region must be balanced with the competing objective of retaining postoperative neurological functioning. The objective of this study was to investigate the role of intraoperative MRI (iMRI) as a complement to existing epilepsy protocol techniques and to compare rates of seizure freedom and neurological deficit in pediatric patients undergoing resection of perieloquent lesions.The authors retrospectively reviewed the medical records of pediatric patients who underwent resection of focal cortical dysplasia (FCD) or heterotopia localized to eloquent cortex regions at the Childrens National Health System between March 2005 and August 2015. Patients were grouped into two categories depending on whether they underwent conventional resection (n = 18) or iMRI-assisted resection (n = 11). Patient records were reviewed for factors including demographics, length of hospitalization, postoperative seizure freedom, postoperative neurological deficit, and need for reoperation. Postsurgical seizure outcome was assessed at the last postoperative follow-up evaluation using the Engel Epilepsy Surgery Outcome Scale.At the time of the last postoperative follow-up examination, 9 (82%) of the 11 patients in the iMRI resection group were seizure free (Engel Class I), compared with 7 (39%) of the 18 patients in the control resection group (p = 0.05). Ten (91%) of the 11 patients in the iMRI cohort achieved gross-total resection (GTR), compared with 8 (44%) of 18 patients in the conventional resection cohort (p = 0.02). One patient in the iMRI-assisted resection group underwent successful reoperation at a later date for residual dysplasia, compared with 7 patients in the conventional resection cohort (with 2/7 achieving complete resection). Four (36%) of the patients in the iMRI cohort developed postoperative neurological deficits, compared with 15 patients (83%) in the conventional resection cohort (p = 0.02).These results suggest that in comparison with a conventional surgical protocol and technique for resection of epileptic lesions in peri-eloquent cortex, the incorporation of iMRI led to elevated rates of GTR and postoperative seizure freedom. Furthermore, this study suggests that iMRI-assisted surgeries are associated with a reduction in neurological deficits due to intraoperative damage of eloquent cortex.


PubMed | Neuropathology and., Neuroradiology. and Childrens National Health System
Type: | Journal: Journal of neurosurgery. Pediatrics | Year: 2016

OBJECTIVE Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy that often may be treated by surgery. Following resection, many patients continue to experience seizures, necessitating a decision for further surgery to achieve the desired seizure outcomes. Few studies exist on the efficacy of reoperation for intractable epilepsy due to FCD in pediatric cohorts, including the definition of prognostic factors correlated with clinical benefit from further resection. METHODS The authors retrospectively analyzed the medical records and MR images of 22 consecutive pediatric patients who underwent repeat FCD resection after unsuccessful first surgery at the Childrens National Health System between March 2005 and April 2015. RESULTS Accounting for all reoperations, 13 (59%) of the 22 patients achieved complete seizure freedom and another 5 patients (23%) achieved significant improvement in seizure control. Univariate analysis demonstrated that concordance in electrocorticography (ECoG) and MRI localization (p = 0.005), and completeness of resection (p = 0.0001), were associated with seizure freedom after the first reoperation. Patients with discordant ECoG and MRI findings ultimately benefited from aggressive multilobe lobectomy or hemispherectomy. Repeat lesionectomies utilizing intraoperative MRI (iMRI; n = 9) achieved complete resection and seizure freedom in all cases. CONCLUSIONS Reoperation may be clinically beneficial in patients with intractable epilepsy due to FCD. Patients with concordant intraoperative ECoG and MRI localization may benefit from extended resection of residual dysplasia at the margins of the previous lesional cavity, and iMRI may offer benefits as a quality control mechanism to ensure that a complete resection has been accomplished. Patients with discordant findings may benefit from more aggressive resections at earlier stages to achieve better seizure control and ensure functional plasticity.

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