4^th World Congress on Parkinsons & Huntington Disease August 29-30, 2018 Zurich, Switzerland

Biography:

Sebastian Knöbel is a trained Biologist and received his PhD at the RWTH Aachen University in 2006. He joined the Miltenyi R&D Department as Research Scientist in 2007.  In his current position as Manager, he heads the Media Development Group and Research Groups for pluripotent, mesenchymal stem cells generating tools and protocols for the isolation, culture and modulation of cells for research and translational applications. His current research includes many aspects of regenerative cell therapy with a focus on the manufacturing of pluripotent stem cell derived cell types.

Abstract:

Pluripotent stem cell (PSC) derived cell products hold great promise for future clinical use in a variety of indications like type i diabetes, cardiomyopathies, macular dystrophies and Parkinson’s disease. For Parkinson’s disease trials, grafted human fetal tissue has indicated utility of tissue or cell replacement therapy. However, the limited availability and ethical implications connected to using primary fetal material have inspired pluripotent stem cell (PSC) based approaches. In vitro differentiated mesencephalic dopaminergic (mesDA) progenitor cells grafted into the striatum have proven to, revert motor symptoms in pre-clinical animal models of Parkinson’s disease compensating for the loss of dopamine producing cells in the substantia nigra. Raising regulatory requirements for such advanced-therapy medicinal products (ATMPs) imply the need for standardized reagents and highly reproducible manufacturing procedures. Automation of PSC expansion, differentiation, and potential product optimization through cell sorting may contribute to successful and cost-effective innovative therapies. Using the versatile and integrated GMP cell processing platform, CliniMACS Prodigy®, we previously developed a cultivation and expansion workflow for PSCs. Now we have adapted the lab protocol for the differentiation to mesDA progenitor cells and have transferred it onto the device, for a medium-scale prototype manufacturing process within the closed system. Extrapolating the cell numbers retrieved from the protoype process would correspond to 150–250 patient doses per manufactured batch. To characterize the identity of the resulting progenitors, we have designed a concise marker panel for flow cytometry-based quality control (QC). Taken together, we have developed a method for adherent, closed-system cultivation of PSCs and differentiation to dopaminergic progenitor cells in combination with comprehensive QC assays.

Biography:

Anita Haahr—RN, MScN, PHD—is a Senior Lecturer at the School of Nursing, Aarhus, Denmark and an Adjunct Lecturer at the Department of Health, section for Nursing, Aarhus University, Denmark. The focus of her research is living and coping with life with PD from a patients and spouses perspective. She has done research within this area for more than a decade and has published several papers on the subject.

Abstract:

Parkinson’s disease (PD) is the second most common chronic progressive neurodegenerative disease affecting more than 10 million people worldwide. The main features of PD are tremor, bradykinesia, rigidity and at the later stage, postural instability. As the disease progresses, non-motor symptoms such as neuropsychiatric symptoms, depression, anxiety, cognitive challenges, sleep disturbances and fatigue may also appear. Thus, living with PD strongly affects daily living and as the disease progresses, individuals living with PD may experience the disease as limiting on a daily basis, requiring the development of individual ways of coping with the disease to maintain an active everyday life. The aim of the study was to identify coping in daily life in individuals with PD as it is described in the existing literature, ultimately to be able to describe coping patterns and challenges, in order to uncover the needs of the individual living with PD, to support their efforts in managing daily life with the disease. In this presentation, we unfold the results of a literature review performed as a meta-ethnographic metasummary and metasynthesis. A thorough literature search was conducted and adhering to the JBI guidelines, eligible studies were assessed for quality. A total of 13 articles were included in the study. Preliminary results shows the overarching motivation for coping with PD to be “striving for normalcy” and “preserving the self” from before PD. These findings will be unfolded at the presentation.

Biography:

Sana A. AlBustan is a young researcher  in the Department of Communication Disorders Sciences, College of Life Sciences, Kuwait University. She earned her Ph.D from the Department of Speech, Language and Hearing Sciences, College of Public Health and Health Professions, University of Florida. Her clinical internship and practicums were in Florida hospitals, public schools and private clinics. In May,2017, Dr. AlBustan  published “Kuwaiti Teachers' Perceptions of Voice Handicap” in the Journal of Voice . In December 2017,  she published” Towards a Standard Arabic System Usability Scale: Psychometric Evaluation using Communication Disorder App” in the International Journal of Human–Computer Interaction

Abstract:

The intended study would shed a light on Parkinson Disease (PD)in Kuwait. This study will represent the levels of awareness and knowledge among general people about PD that are currently not very well documented in Kuwait. A questionnaire will be developed  for this current study by the researcher that would consist of a structured item questionnaire that would compose of both open-ended and close-ended questions would be given to 50 males and  50 females after a committee of professionals in  the field approve the questionnaire. Questions will be devolved to address  various aspects of the  definition PD,  onset of PD, cause, treatment, and hereditariness Demographic data with participants demographic features such as age, gender, occupations, qualifications and educational level will also be considered and addressed in this research. SPSS analysis procedures will be used to examine and analyze the participants responses The study is still in its pre implementation stage progress. The researcher anticipates her results will be consistent with other researchers findings. The primary goal of this study is  to investigate the level of public awareness and knowledge of PD and facilitate the level of awareness and the services offered by governmental and private medical facilities in the Kuwait

Biography:

Jae Moon Lee completed his PhD from Duke University and Post-doctorate from Duke University School of Medicine. He is the VP of Kainos Medicine, a clinical stage Korean biotech company. He has published more than 15 papers in reputed journals.

Abstract:

Current standard of care for Parkinson’s disease is symptomatic treatments by supplementing dopamine or dopamine agonists or analogous mechanisms, and the disease modifying treatment is one of the major unmedical needs to block the progression. KM-819 is an orally active small molecule drug developed as an inhibitor for FAF1, a proapoptotic protein, targeting various degenerative diseases. It has shown superior efficacy of neuroprotection in cell models and of dopaminergic neuron protection in midbrain in various animal models of Parkinson’s disease as well as improvement of behavioral tests, suggesting this drug has potential capability of slowing or stopping the progression of the disease. It has also shown inhibition of alpha-synuclein accumulation in cells. We have completed Phase 1 clinical trial for KM-819, randomized, double-blind, placebo-controlled study. The study is divided into part A (single ascending dose) and part B (multiple ascending dose) for evaluation of safety, tolerability, and pharmacokinetics as well as various pharmacodynamics markers for KM-819 in healthy volunteers. The study results showed no drug-related serious AEs and high safety profile in human. Also, the PK study showed dose-proportional exposure with higher in elderly group, ideal for Parkinson’s drug. We are currently planning for phase 2 in patients focusing on investigation of the drug’s efficacy of slowing down or halting the progression of the disease.

Biography:

Jae Moon Lee completed his PhD from Duke University and Post-doctorate from Duke University School of Medicine. He is the VP of Kainos Medicine, a clinical stage Korean biotech company. He has published more than 15 papers in reputed journals.

Abstract:

Current standard of care for Parkinson’s disease is symptomatic treatments by supplementing dopamine or dopamine agonists or analogous mechanisms, and the disease modifying treatment is one of the major unmedical needs to block the progression. KM-819 is an orally active small molecule drug developed as an inhibitor for FAF1, a proapoptotic protein, targeting various degenerative diseases. It has shown superior efficacy of neuroprotection in cell models and of dopaminergic neuron protection in midbrain in various animal models of Parkinson’s disease as well as improvement of behavioral tests, suggesting this drug has potential capability of slowing or stopping the progression of the disease. It has also shown inhibition of alpha-synuclein accumulation in cells. We have completed Phase 1 clinical trial for KM-819, randomized, double-blind, placebo-controlled study. The study is divided into part A (single ascending dose) and part B (multiple ascending dose) for evaluation of safety, tolerability, and pharmacokinetics as well as various pharmacodynamics markers for KM-819 in healthy volunteers. The study results showed no drug-related serious AEs and high safety profile in human. Also, the PK study showed dose-proportional exposure with higher in elderly group, ideal for Parkinson’s drug. We are currently planning for phase 2 in patients focusing on investigation of the drug’s efficacy of slowing down or halting the progression of the disease.

Biography:

Abstract:

This study intends to explore the challenges faced by teachers and parents of children with epilepsy during school years. It also aims to provide useful information about the parent-teacher collaboration for the benefit of the pupils, the families and the school.

Methods: Telephone interviews were conducted based on open-ended questions, with 70 head-teachers from schools from all Greek regions. Furthermore a questionnaire was distributed to 100 Greek schools. Additionally, personal interviews took place with 91 parents of children with controlled epilepsy during their school years. The data were grouped and analyzed with the use of qualitative and quantitative analysis.

Results: 89.9% of the school staff was found to know what epilepsy is. 85.1% of the teachers were informed about pupils’ epilepsy by their parents/caregivers while 63/70 head-teachers declared that parents usually misinform the school staff about their child’s condition. 76/91 parents/caregivers personally informed only the head-teacher about their child’s condition because of fear of social stigma and bullying. 87/91 parents declared that they did not know where to seek help to cope with their child's illness apart from their doctor. 92.6% of the teachers felt insufficiently trained to deal with a seizure and 96.2% expressed the need for more formal information about epilepsy. 64/70 head-teachers and all the parents/caregivers expressed the need for inclusion of experts like social workers and nurses into the school personnel.

Conclusion: Epilepsy is a condition that affects not only the pupil with the disorder but also his/her family as well as the school staff. For the school personnel, it is very important to cooperate with the pupils’ parents/caregivers in order to handle the child’s condition properly and safely. The doctor’s guidance to the parents is crucial for their communication with the school staff.

Biography:

With a corporate finance background, after her successful temporal lobectomy in 2013 and continued recovery from psychological diagnoses, Torie has became an active international public speaker and corporate consultant regarding epilepsy, disability, mental health, diversity and inclusion.

Her purposes are to enlighten the uneducated, reduce the stigma held against those with disabilities (particularly epilepsy), and hold organisations accountable for corporate social responsibility when it comes to employment.

Featuring on UK BBC London, 5Live, talkRadio, US Brain Waves Audio and Australian Noongar Radio, Torie’s BBC3 YouTube video in which she featured: “Things Not to Say to Someone with Epilepsy” has been viewed more than half a million times.

Featuring neurological professionals, patients and employers from all over the world, Torie:

• Both founded and frequently writes for both the torierobinson.com and epilepsysparks.com blogs;
• Co-founded the Cheeky Sparks epilepsy podcast;
• Filmed for NHS70
• Works with DWP (UK Government) regarding disability employment;
• Has attended meetings within UK Parliament;
• Is an Epilepsy Action Accredited Volunteer (Trainer), and;
• Has featured in Huffington Post

Torie plays the piano, enjoys communicating to overseas audiences and forever learning more about neurology and cosmology.

Born in the UK, Torie grew up in both England and Australia and has worked for international firms with staff in Europe, Australia, the US and Asia. Torie lives in London with her partner.

Abstract:

Patient in early 30s with refractory, left temporal lobe epilepsy in a setting of left hippocampal sclerosis. Increase in seizure severity and freqency over 25 years, with worsening depression. Patient working in corporate environment.

Aim:

To decrease frequency and/or severity of seizures; increase quality of life and life expectancy

Treatment:

Likely Cause of Epilepsy:

• Lengthy febrile seizure aged 6months

Past AEDs tried:

• Sodium Valproate, Levetiracetam, Phenytoin

AED side effects experienced:

• Memory function decrease, fatigue, numbness (phenytoin), mood instability (Levetiracetam)

Seizure triggers:

• Sleep deprevation, anxiety, forgetting AEDs

Further Diagnosis Related to Epilepsy/AEDs

Surgery Exploration Testing:

• Video Telemetry
• EEG
• fMRI
• Psychological evalutation/neuropsychology assessment inc IQ
• Full understanding of surgery risks and potential outcomes by patient

Surgical Procedure:

• Left Temporal Lobectomy, Feb 2013
• CSF leak followed, leading to suture of the wound

Post-operative Diagnoses Included:

• Severe depression, extreme problems with memory, and exhaustion (for 6-12months)
• Blind spot in right eye
• 5 tonic-clonic seizures post surgery, last in November 2017
• Irregular complex partial seizures (average 4/5 per year)

Current Drugs:

• Levothyroxine 50mg QD
• Lamotrigine 100mg BD
• Lacosamide 100mg BD
• Venlafaxine 150 BD
• Clobazam 10mg

Conclusion:

Status: outcome Engel class 2

Patient has experienced significant decrease in number and severity of seizures. Along with psychological therapy, patient’s quality of life is greatly improved. Despite continued taking of AEDs, and infrequent seizures, the results of surgery is considered to be a success by patient. Patient has greater focus, continues to travel and has supportive partner and friends.

Biography:

Elaine Wyllie, Professor, Cleveland Clinic Lerner College of Medicine, is a world renowned thought leader in neurology and epilepsy. Dr. Wyllie has been on the Castle Connolly list of America’s Best Doctors for many years, as well as on several other national and regional Top Doctors lists. Her many honors and awards include the highly competitive Award for Outstanding Work in Epilepsy Research from the American Epilepsy Society and Honorary Membership in the Canadian Association for Child Neurology.

Abstract:

New research in pediatric epilepsy surgery is providing opportunities to help more children than ever before.   Some of our most exciting results have been in children with early focal brain lesions and diffuse EEG abnormalities.  The diffuse findings on EEG reflect the evolution of the epilepsy as the early focal lesion, usually cerebral infarction or malformation of cortical development, interacts with the brain at different stages of development.  Infants with focal lesions tend to manifest with hypsarrhythmia, and the older children tend to manifest with slow spike wave complexes and other patterns, but in both age groups the epilepsy typically disappears when the lesion is removed.  Wyllie and colleagues studied 209 children with an early focal lesion who underwent epilepsy surgery, and found no significant difference in seizure outcome based on presence or abundance of generalized epileptiform discharges and EEG seizures.

A second exciting new opportunity for pediatric epilepsy surgery has emerged for children with bilateral abnormalities on brain MRI. Hallbook and colleagues reviewed preoperative MRIs in 110 children who underwent hemispherectomy at Cleveland Clinic, and found abnormalities on the contralateral side in 74%.  In a follow up study of 170 children who underwent hemispherectomy, Moosa and colleagues found that contralateral MRI findings had no significant impact on the frequency of seizure-free outcome among Cleveland Clinic’s highly selected cases.  The contralateral MRI abnormalities in these children, although not insignificant, were always less extensive and less prominent than those on the side of hemispherectomy. 

Research suggests that for patients of all ages, shorter epilepsy duration may positively affect postoperative seizure outcome.  By recognizing surgical opportunity and shortening the delay, we can help more children than ever before. 

Biography:

Laurice Yang earned a Master’s Degree in Health Administration at the University of Southern California where she received the high honor as a Dean Merit Scholar. She went on to obtain her Medical Degree from the University of Vermont and completed her Neurology Residency at the University of Southern California where she was appointed Neuroscience Chief Resident and spent the year revamping the entire medical student/resident education curriculum. She completed her clinical training as a Movement Disorders Fellow at the University of California in Los Angeles under Dr. Jeff Bronstein. She is a board-certified Neurologist, specializing in the diagnosis of movement disorders including Parkinson’s disease, atypical parkinsonian disorders, essential tremor, and Huntington’s disease. She has an interest in dystonia and spasticity and has been trained to perform botulinum toxin injection under ultrasound guidance to better ensure accuracy and efficacy with each procedure. She has also presented lectures on topics in dystonia, education, and healthcare administration for CME (Continuing Medical Education) faculty development courses and at the American Academy of Neurology.

Abstract:

Dystonia is a characterized by intermittent, abnormal and often repetitive muscle contractions. The diagnosis of dystonia can often be difficult to assess due to the variability and complexity of the disease. During this lecture, we will first review the historical context of how dystonia was discovered and how the clinical understanding of dystonia had evolved over the last several decades. We will discuss the clinical characteristics of the most common types of dystonia and review how to accurately describe and categorize this very complex disease. We will also review the medical treatment options and discuss the efficacy of botulinum toxin as well as techniques on how to be more accurate during the injection procedure. We will explore the other types of treatment such as sensorimotor retraining therapies, which takes advantage of the neuroplasticity of the brain to help “relearn” normal movement. And lastly, we will explore the surgical options that are available now as well as other types of procedures that could supplement the current treatment options. The learning objectives for this presentation are: Understanding the main diagnostic components of dystonia; being familiar with the different types of dystonia; describing medical and surgical treatment; and describing sensorimotor retraining and its role in those who have dystonia.

Biography:

Kambiz Hassanzadeh is the Associate Professor and Head of Cellular and Molecular Research Center at Kurdistan University of Medical Sciences, Iran. He teaches Pharmacology and Neuroscience courses to Medical and PhD students and does research in the field of Neuroscience with more than 60 publications. During recent years, he has been interested in doing research on molecular nature of neurodegenerative diseases, especially Parkinson’s disease. He also researches on antioxidant agents on animal models of Parkinson’s disease.

Abstract:

Current Parkinson’s disease (PD) therapies are focused on maintaining dopamine levels of brain at normal range. Although, this approach is fairly useful to control and manage Parkinson’s disease symptoms, it has some disadvantages. Previous studies indicate that levodopa and other dopaminergic medications accelerate neuronal degeneration in some parkinsonian brains via production of free radicals and reactive oxygen species (ROS). This is in addition to the main oxidative and inflammatory processes of the PD. Additionally, patients need higher doses of drugs over the time which it implies some serious side-effects including motor and non-motor signs. Oxidative stress and inflammation are considered as the leading cause and progression in many diseases, especially those that are associated with aging such as Parkinson’s disease. During the recent years, interest in administration of neuroprotective factors such as anti-oxidants, anti-inflammatory drugs and neurotrophic factors for management of PD is popularly increasingly. According to the above literature, it is important to understand the mechanism of action of these neuroprotective factors and investigate the new and more effective ones. On the other hand, neuroinflammation is one of the serious complications of PD which is usually developed due to protein aggregates and dopaminergic cell deaths. Therefore, here we review the pathways of these two important aspects of PD (oxidative stress and neuroinflammation) to understand what is happening inside a PD brain and we discuss about the benefit of anti-oxidants and anti-inflammatory drugs based on our recent studies in this area.

Biography:

Byung-Jun Park completed his PhD and Korean Doctor in Medicine Degree at the College of Korean Medicine, Daejeon University, Daejeon, South Korea. He has opened a Young Jin Korean Medicine Clinic, and his clinical speciality has been the treatment of Parkinson’s disease and movement disorders since 1995. He has published multiple papers on Parkinson’s disease in reputable journals and is a Member of the Movement Disorder Society. He was listed in the Marquis Who’s Who in the World in 2017–2018.

Abstract:

Parkinson’s disease (PD) is a neurodegenerative disorder involving abnormal body movements. The degenerative loss of dopaminergic neurons in the substantia nigra leads to the onset of PD symptoms, including slow movement, tremor, stiffness, and abnormal posture. Because L-3,4-dihydroxyphenylalanine (L-DOPA) treatment is very effective for symptom inhibition, it is the most widely prescribed treatment of patients with PD. However, long-term L-DOPA treatment is not recommended because of its serious side effects, including dyskinesia. Moreover, L-DOPA does not prevent the progression of PD. Therefore, a novel therapeutic approach is greatly needed for PD. Hepad, a herbal medicine, consists of six Korean medicinal herbs that were selected based on Korean medicine theory. The treatment of patients with PD using Hepad has been clinically effective. In addition, Hepad treatment reduces the required doses of conventional PD drugs, and some patients were able to terminate conventional PD treatments without additional symptom manifestation. A preclinical study has reported that Hepad prevents neuronal cell death by suppressing the production of reactive oxygen species. These neuroprotective effects of Hepad have also been observed in animal experiments. Hepad treatment in a PD animal model increased dopaminergic neuron number and dopamine levels in the substantia nigra to similar or higher levels than those in L-DOPA-treated animals. Considering the complexity of PD, a multi-targeted approach with multiple compounds would be more effective than single-compound treatment. Taken together, these results suggest that Hepad, a mixed Korean herbal medicine, would be an effective treatment for patients with PD.

Biography:

D’Auria Stanislao  graduated in Medicine in 2003 did a specialization in Neurosurgery in 2008 from Second University of Naples, School of Medicine. Since 2008, he works as a Neurosurgeon at the Department of Neuroscience of Santa Maria della Misericordia in Udine, Italy. His fields of interests are Functional Neurosurgery and Neuromodulation and Neuro-Oncology. He has published more than eight papers in reputed journals and has been involved in many international congresses.

Abstract:

In the last 20 years, thanks to technological development and still ongoing innovations in features and materials of implantable devices, deep brain stimulation (DBS) has become one of the most effective, reliable and safe surgical procedure for treatment of many different movement disorders.  The clinical condition that has been better treated with such a technique is Parkinson’s disease. Nevertheless, many other diseases today are good indications for DBS like dystonia, essential tremor and Giles de la Tourette syndrome. Many papers say that DBS is like a “gold standard” in patients affected by dystonia or Parkinson's disease when pharmacological intake alone doesn't work or has lots of troublesome collateral effects. Since 2010, we started to use a stereotactical frameless technique. We noticed a real improvement in patients in terms of comfort, tolerability and reduced pain during surgery. At the same time, we obtained a very good precision in targeting, comparable to those of classical frame based surgery. Innovations, mostly in hardware such as leads, extentions and IPG, go on. We recently started to implant a new lead's generation named, “directional leads”. This lead has many different splitted contacts that allows the clinicians to steer the electrical field mostly wherever they want through the nervous tissue, obtaining clinical effect far from brain area, so as to avoid collateral effects. Since March 2016, we have performed 14 bilateral implantations for Parkinson’s disease and dystonia. At the time of reglage, when collateral effects like motor evoked unwanted responses or limbic effects have been elicited, switching the “hemi-contacts” allowed to make them disappear without any reduction in the desired beneficial effect. An issue we faced, was how to standardize all implanted patients, a shared rotational position of leads. As such, the clinicians can establish a number for any single contacts in order to compare results in different patients and in the single one over time as well. We also did not have an X-ray checking system in the Nexframe device, like basically any head-mounted and pin-fixed traditional stereotactical system has in itself. In other words, we needed a method that allowed to figure out the position of leads. We took two markers behind the ears to allineate during intraoperative X-ray checking. This brought to correct alignment of the lead's reference markers visible at the top of the whole group of contacts. In conclusion, even though the number of patients is low, we believe that directional leads bring to excellent results in terms of shaping of stimulation. They are a powerful tool in the hand of programmer clinicians, potentially able to improve the outcome of the patients. Splitting of contacts gives the chance to get a higher number of contacts allowing the clinician to choose among many stimulation's combination. Moreover, directional leads technology gives us the possibility to steer and deform the tridimensional electrical field shape. Warping and bending of electrical field, brings to a better results for patients, both lessening side effects and enhancing the positive benefits of stimulation. Our easy and reliable intraoperative tecnique is effective to correctly alineate in the same orientation the two leads of both sides.

Biography:

Abstract:

Objective: 

The Objective of this study is to examine the natural courses of Alzheimer Disease (AD), Light Cognitive Failure (LCF) and Parkinson ‘s Dementia (PD) cases free of any therapeutic procedure and with neuropsychological test series; to determine the transformation ratio of these cases to dementia and to examine the courses of clinical factors. 

Tools and Method: 

120 patients consisting of 72 AD, 16 PD and 32 LCF patients and 24 healthy controls who are the spouses of the patients or healthy volunteers, who have applied to Mersin University Faculty of Medicine Education and Research Hospital Neurology Department between years 2007 and 2016, have been included in the research.

Patients have been invited to control visits once every 6 months and healthy individuals have been invited to control visits once a year.

Findings:

In the patient groups, functionality and DLA scores have considerably failed in comparison with the scores of control group. In the LCF group, MMSE, forward and backward counting range, calculation, abstraction, praxis, memory of word list, understanding, construction, clock drawing scores have been higher than the other groups but lower than the control group. In the LCF group, total NPI and NPI trouble scores have been lower than the other groups.  In the PDgroup, total NPI scores have been determined to be higher than the AD and LCF groups. Total NPI trouble score has been higher for the AD group when compared with PD and LCF groups. In the LCF group, for 11 % of the patients, diagnosis have transformed to AD in the control period. In the control visits, MMSE values of the control group have risensignificantly after the second visit. In the LCF group, falls in word list memory scores which are statistically meaningful have been determined in the first and third trials.

Result: 

In our study, we determined that 11,1% of the patients with LCF cogenesis had transformation to AD, in this group no transformation to PD has been observed in the control time, no transformation in the healthy control group has been observed.

Biography:

Rapita Naresh Sood has completed her PhD from University of Haifa Israel and presently doing her Postdoctoral studies from Goodman Cancer Research Center, McGill University in the laboratory of Dr. Nahum Sonenberg. She has published eight papers in reputed journals and has also received the Richard and Edith Strauss Fellowship which is a McGill Internal fellowship award for one year. Also, her project on epilepsy is giving a new direction to rescue the mTOR pathway which is a new perspective for future therapy of epilepsy.

Abstract:

Epilepsy, a common neurological disorder characterized by recurrent seizures that are unpredictable and sometimes progressively severe affecting 50 million people worldwide. Mutations in TSC1/2, PTEN and FMR1 genes cause Tuberous Sclerosis, PTEN hamartoma syndrome and fragile X syndrome respectively and lead to intellectual disability, autistic-like behaviour and epileptic seizures. Mutations in these genes cause upregulation of mTORC1 signalling, however the role of mTORC1 downstream effectors, such as 4E-BPs and S6K, in the pathophysiology of the disorders is not well understood. In the current project we set out to study the contribution of cap-dependent translation and 4E-BP2, downstream of mTORC1, in the susceptibility to seizures. Our previous study showed that deletion of 4E-BP2 leads to autism-like phenotypes and imbalance of excitatory to inhibitory synaptic activity. We recently found that eIF4ebp2 KO mice show reduced threshold to seizure-inducing agent (PTZ) at concentration of 70 mg/kg IP. As part of this project we would like to see whether inhibition of eIF4A would rescue or attenuate the seizure phenotype. The first experiment we are planning is to inject intraperitoneally WT and eIF4ebp2 KO mice with vehicle and eIF4A inhibitor. The experimental studies is still going on and furthermore, is needed to understand the role of mTOR signaling pathway in epileptogenesis, and that it may be a target for the development of novel therapies that eliminate the progressive effects of seizures.

Biography:

Farnaz Nikbakht, before obtaining her PhD degree in Human Physiology from Shiraz University in 2007, she received an award from the Iran Ministry of Health and Education; she spent six months at Flinders University, Adelaide, Australia for completing her research on degenerative diseases. Now, as the Associate Professor of Department of Physiology, Iran University of Medical Sciences, she has managed several research programs and has conducted the thesis of several Masters and PhD students in her Lab. Since 2010 she has directed a research team on Epilepsy and Alzheimer’s diseases fields in her lab. Her research leads to publishing several articles.

Abstract:

Background: Current medications for epilepsy are just anticonvulsive agents and cannot protect against epileptogenic processes. On the other hand, theses anticonvulsive drugs are ineffective for one-third of epilepsy patients. Regarding these limitations, there is an urgent and growing need for a new drug to process both properties. Metformin, a common antidiabetic drug, has been shown to act as an anticonvulsive drug in some experimental models. However, the antiepileptic properties of metformin are not yet clear.

Materials & Methods: Sixty male Wistar rats are divided randomly into four groups: control, kainate (KA group), metformin+KA group and metformin group. Temporal lobe epilepsy was induced by intracerebroventricular (ICV) microinjection of 0.5 µg KA. Metformin was orally administered, starting two weeks before epilepsy induction. Following epilepsy induction, animals were monitored for behavioral seizure severity. Epileptogenesis was assessed by evaluating four factors: Hippocampal neuronal loss and neurodegeneration using Nissl and Fluoro Jade B(5 days after surgery); Neurogenesis using BrdU (5 days after surgery); Mossy Fiber sprouting, using Timm staining (30 days after surgery) and; EEG (30 days after surgery).

Results: Metformin as an anticonvulsant drug: the latency to seizure and the seizure severity were both reduced significantly, following metformin treatment (P<0.001). Metformin as antiepileptic drug: According to the Nissl and Fluoro-Jade B staining, the best protected areas in the hippocampus after metformin administration were CA3 and hilus (P<0.00). Behavioral EEG monitoring revealed that metformin-treated rats displayed spontaneous seizures at lower frequencies compared with epilepsy group. Metformin alone increased the neurogenesis which was even greater than Ka-induced neurogenesis. However, metformin-treated rats after epilepsy showed the immigration of new neurons to the hilar and CA3 areas. Metformin also reduced significantly mossy fiber sprouting.

Conclusion: Altogether we conclude that metformin acts not only as an anticonvulsant but an antiepileptogenic drug. 

Biography:

Abraham Ratna Joseph Nayakanti is an Assistant Professor in the Human Structure and Function Department, Avalon University School of Medicine, Curacao. He is a PhD Scholar in the Department of Anatomy in the Field of  Embryology of Renal Morphogenesis and Histogenesis, Faculty of Medicine at Vinayaka Missions University  and has completed his Master’s degree in Medical Anatomy at SVIMS University, India and has more than six years of teaching experience in various medical universities in India and abroad with presentations and publications in various international conferences and medical journals of anatomy and research. He has Successfully comleted Online course in Essential Skills in Medical Education, given by Association of Medical Education in Europe (AMEE) under Dundee University, Scotland.

Abstract:

Neural tube defects are very rare untill they are found in repeated deliveries. During routine collection of fetuses for the morphometrical and histological studies of renal developmental study, we found a rare anomaly with the defective closure of the cranial neuropore resulting in anencephaly. The case study consists of Intra uterine dead fetus with anencephaly which has spontaneously aborted. Service of Salem Polyclinic Hospital, in giving male aborted fetus for the study with the parent consent is appreciable. The diagnosis of suspected anencephaly was made on average at 21.3 weeks of gestation. The crown rump length was 14 cm and the crown heel length measurement of the fetus was 22 cm. In general there are various conginetal neural anomalies which appear to be similar to anencephaly.

Biography:

Arindam Ghosh Mazumder is a Senior Research Fellow, currently pursuing his PhD from CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India. He was awarded DST-INSPIRE Fellowship for pursuing PhD, sponsored by the Department of Science and Technology (DST), Government of India, 2013.

Abstract:

The role of mammalian target of rapamycin (mTOR), an evolutionary serine/threonine protein kinase, has been well documented in several disorders. In epilepsy research, mTOR pose as a very exhilarating target, as inhibition of its hyperactivation has been found to be effective in suppression of epilepsy and epileptogenesis. However the precise mechanism for the aberrant expression of mTOR, leading to the overexpression of its downstream genes, still remains blurred. Preclinical and clinical studies have revealed that decrease in PI3K/AKT/mTOR pathway hyperactivation have considerably reduced seizures. Hence, our study was designed to explore the anti-seizure potential of selective PI3K inhibitor (morpholine containing compound) on zebrafish model of pentylenetetrazole induced seizure. Zebrafish larvae of 7 days post fertilization were subjected to different concentrations of the selective PI3K inhibitor, following which they were exposed to pentylenetetrazole and recordings were scored on a 3 point scale. The best therapeutic concentration was selected and it was tested on adult zebrafish. Furthermore, fish brains were isolated and expressions of genes were studied in comparison to the epileptic fish. The results showed that the inhibitor distinctly reduced the seizure state in both larvae and adult fish in combination to decreasing the expression of various genes of the PI3K/AKT/mTOR pathway. These findings concluded that selective PI3K inhibitor has anti-seizure potential and can be explored in the near future as a potential antiepileptic.