A study recently published in the journal Human Molecular Genetics by Marni J. Falk and colleagues from the Mitochondrial-Genetic Disease Clinic at The Children's Hospital of Philadelphia (CHOP) holds great promise for developing new treatments for patients with mitochondrial disorders

Extra-mitochondrial mechanisms including dysregulated translation and the increased autophagy contribute to the pathophysiology of respiratory chain disorders. They showed that drugs which partially inhibit these cellular processes offer novel treatment strategies in mitochondrial disorders. 

In translation, messenger RNA (mRNA) which is produced by transcription from DNA is decoded by cellular ribosomes to produce a specific amino acid chain, or polypeptide. Autophagy is the basic cellular mechanism by which unnecessary or dysfunctional cellular components are degraded by lysosomal action. Both these processes have been shown to be dysregulated in mitochondrial disorders. 

Falk's team showed that nicotinic acid, a form of vitamin B3 (niacin), improved lifespan and metabolism in a mitochondrial disease animal model, microscopic C. elegans worms, by restoring normal activity to cellular signalling pathways. Rapamycin, an antibiotic and immunosuppressant, improved kidney disease in mice with a mitochondrial disorder caused by coenzyme Q deficiency by directly inhibiting the central translational regulator (mTORC1). Probucol (used in the past as a cholesterol-lowering drug) which also inhibits mTORC1 improved lifespan and physiological functioning in worms with mitochondrial respiratory chain complex I deficiency Partial inhibition of translation by cycloheximide an antibiotic, or of autophagy by lithium chloride, prescribed for patients with bipolar disorder, improved viability, preserved cellular respiratory function and induced mitochondrial translation. 

These findings offer novel treatment strategies in the diverse array of mitochondrial disorders involving respiratory chain dysfunction. Further research should investigate how specific subgroups of patients with mitochondrial disorders could benefit from these and similar drugs. Mitochondrial Disease Clinical Center at CHOP is planning early-stage clinical research trials to investigate these novel treatment strategies further.

Peng, M., Ostrovsky, J., Kwon, Y. J., Polyak, E., Licata, J., Tsukikawa, M., … Falk, M. J. (2015). Inhibiting cytosolic translation and autophagy improves health in mitochondrial disease. Human Molecular Genetics, 24(17), 4829–47. doi:10.1093/hmg/ddv207

On behalf of the International Child Neurology Association, it is my great pleasure to welcome you to the 14^th International Child Neurology Congress being held in Amsterdam, the Netherlands, from May 1-5th, 2016. Our congress theme is 'Bridging Worlds' with the aim of providing an appreciation of Childhood Neurological Disorders from a Global Perspective with strong representation from all six major geographic regions. 

The scientific program will feature internationally recognized experts who will provide the latest advances in different subspecialties of child neurology combined with a strong educational program through breakfast courses, meet the expert sessions and master classes. We also hope to facilitate open dialogue between clinicians and neuroscientists from resource-limited and resource- enriched regions in order to lay the groundwork for future collaborative research networks. These networks would link clinicians involved in the careful phenotyping of unique clinical populations afflicted with specific neurological diseases with researchers in state-of-the-art research laboratories directed toward characterizing the genotypes and creating in vitro and in vivo disease models, in order to increase understanding of the underlying pathophysiological disease mechanisms, for the development of specific interventional therapies. These new therapies could then be translated back to the clinical populations and be rigorously tested through prospective randomized double-blind controlled clinical trials to evaluate the true efficacy of the new therapies. This would benefit the affected children and their families, their caregivers and the investigators, thus moving the field forward. This will also set the stage for the launching of our research portals on www.ICNApedia.org for the linking of clinical and basic science investigators.

Several exciting new ICNA initiatives will be launched at the ICNC2016 as follows: 

• There will be a presentation of the results of the first funded Global Burden of Disease Seed Grants. These competitive seed grant opportunities, which have been offered through ICNApedia.org to neurology residents, fellows and junior staff, aim to capture pilot data on the global burden of neurological morbidity, quality of life, and mortality specific to major neurological diseases in resource-limited regions (e.g. CNS Tb, HIV, malaria, CP). These pilot proposals consist of 2-3 month international fellowships linked to established investigators at target sites which have high prevalence for a given disease (e.g. current sites include South Africa, Botswana, India) where study ethics approval is in place along with robust epidemiological study design. This pilot data will then form the basis for future large scale epidemiologic studies by the senior investigator with the ultimate goal of generating recommendations for targeted cost-effective, site-specific improvements in health care policies, in conjunction with the local health care services and infrastructure (Health Policy Level). 
• A symposium will be dedicated to a review of the integral components of solid clinical research methodology and rigorous study design along with the application of appropriate statistical methodology. There will also be a review of the CONSORT guidelines for writing clinical research papers and information will be provided on existing courses and sites offering training in these methodologies. 
• The ICNC2016 will also mark the launching and first meeting of the Council of the Future Leaders of ICNA who will be comprised of outstanding, regionally nominated senior child neurology residents, fellows and junior faculty who will meet in Amsterdam to establish their mandate, goals for the future clinical, research and educational programs of ICNA, metrics for success in achieving these goals and perceived obstacles. They will also form the first editorial board for the Resident and Fellow section of our new electronic journal JICNA. 

Please join us for a scientifically stimulating ICNC2016 program in an atmosphere of warm collegiality set in the elegant city of Amsterdam which embodies Old World Charm amongst seas of vibrant multicoloured tulips and myriads of historic canals and bridges in the home of the magnificent works of Van Gogh and Rembrandt.

​Ingrid Tein
President
ICNA

Roberto Caraballo graduated from Medical School of the University of Buenos Aires, Argentina, and received his training in pediatric neurology at the Pediatric Hospital Pedro de Elizalde in Buenos Aires under the mentorship of Dr. Natalio Fejerman. In 1988-1989 he did a visiting fellowship at the Reparto di Neurosichiatria Infantile of the Ospedale Borgo Roma, University of Verona, Italy, under Prof. Bernardo Dalla Bernardina with whom he has a continued close scientific collaboration. He did a further training at the Seizure Unit of Miami Children's Hospital, Miami, USA directed by Dr. Michael Duchowny and in refractory epilepsy at the Reference Center for Refractory Epilepsy at Ghent University Hospital, Belgium directed by Prof. Dr. Paul Boon. He started working as a pediatric neurologist/epileptologist at the Pediatric Hospital J.P. Garrahan in Buenos Aires in 1990 and is currently chairman of the Division of EEG and Video Monitoring and Coordinator of the Refractory Epilepsy Clinic at the Department of Neurology at the same hospital. 

Dr. Caraballo has published more than 120 peer-reviewed articles and 46 book chapters and was coauthor of 6 books contributing to the knowledge on and recognition of many different epileptic syndromes, mainly benign focal epilepsy in infancy, childhood and adolescence focusing not only on electroclinical features, treatment, and outcome, but also on genetic aspects. He has also participated in consensus groups on the ketogenic diet, on the electroclinical definition and therapeutic management of epileptic encephalopathies, and on the global management of refractory epilepsy, such as Rasmussen encephalitis, mesial temporal lobe epilepsy secondary to hippocampal sclerosis, and focal cortical dysplasia. 

Among his teaching activities, Dr. Caraballo is in charge of the practical works in the course of pediatric neurology at Medical School of the University of Buenos Aires and was a faculty member of at the Venice International School of Neurological Sciences for the international course on epilepsy and for the Latin American Summer School of the ILAE. 

Dr. Caraballo worked for the Panamerican Health Organization (PAHO) as an advisor on epilepsy in 1999 and as a local investigator in Argentina for International Program "Epilepsy out of the Shadows", of the WHO-PAHO, ILAE, and IBE between 2001 and 2003. Within this latter framework he carried out a pilot project in Gualygualchú, Argentina, to raise awareness of epilepsy among the general population through the education of priests and teachers. He was a member of the Commission on Pediatrics of the ILAE between 2001 and 2005 and currently participates in the commissions on Neurophysiology and on Autism of the ILAE. 

He has been a member of the editorial board of Epilepsia since 2010 Currently, Dr. Caraballo is president of the Argentine League against Epilepsy for a second term and member of the ICNA Executive Board.