Third Joint Symposium
New Frontiers in Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation: From Benchside to Bedside
Contributed by Ruth H. Walker, MB, ChB, PhD
Department of Neurology
James J. Peters Veterans Affairs Medical Center
New York, NY, USA
Department of Neurology, Mount Sinai Medical Center, New York, NY, USA
The Third Joint Symposium on New Frontiers in Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation: From Benchside to Bedside was held recently to focus upon these rare basal ganglia neurodegenerative disorders.
The symposium took place at Stresa, on the shores of Lake Maggiore, Italy, October 30-November 1, 2014.
The meeting was organized by Lucia de Franceschi (University of Verona), Sonia Levi (Vita-Salute San Raffaele University, and the San Raffaele Scientific Institute, Milan), and Valeria Tiranti (IRCCS Foundation Neurological Institute Carlo Besta, Milan).
This meeting continues to expand upon the formal collaboration between researchers studying these two groups of very rare disorders which was developed at the first joint meeting in Bethesda in 2010. The current meeting brought together an international group of clinicians and basic scientists from a wide variety of disciplines, and was attended by over 120 participants. Patient group representatives, family members, and affected patients from around the world also met in parallel and participated in a joint session.
The meeting was generously supported by the International Parkinson Disease and Movement Disorder Society (MDS), in addition to: Advocacy for Neuroacanthocytosis Patients, AISNAF, AOUI-Verona, ApoPharma Inc., AISNAF, EMINA-2, European Science Foundation, Instituto Neurologico Carlo Besta, NBIA Alliance, Ospedale San Raffaele, the European COST action proteostasis, Retrophin, Sistema Sanitario Regio Lombardia, TIRCON, Universita degli Studi di Verona, Universita Vita-Salute San Raffaele.
Three early-career investigators were awarded scholarships from the NBIA Alliance to attend the meeting, with the aim of fostering collaboration with more senior scientists in the field, and to support their continued contributions to the field; Dr. Claudia Saraceno from the University of Brescia, Italy; Dr. Sarah Wiethoff from the Institute of Neurology, University College London; and Dr. Stephen P. Zano from St. Jude Children’s Research Hospital in Memphis, TN, USA.
Significant progress has been made since the last joint NA/NBIA meeting in Ede, the Netherlands in 2012. The TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration) project, the first double-blind, placebo-controlled study in pantothenate kinase-associated neurodegeneration (PKAN), is underway and is very successfully recruiting patients. There are other promising compounds for NBIA disorders in the pipeline. New molecular techniques such as whole exome sequencing have led to the identification of new NBIA genes, and to expansion of the clinical phenotype of previously-identified genes.
Work continues in the study of the effects of mutations affected genes in a number of model systems. 13 years after the discovery of the chorea-acanthocytosis (ChAc) gene VPS13A, the first substantial insights into the function of chorein, its coded protein, were presented, utilizing disease models in Drosophila, yeast, the slime mould dictyostelium, and human induced pluripotent stem cells. Studies were presented of ion transport dysfunction in erythrocytes in the even rarer McLeod syndrome. Two other members of the VPS13 gene family were discussed; VPS13B, which is responsible for Cohen syndrome, and VPS13C, which was recently linked to frontotemporal dementia, thus suggesting a potential link with neurodegenerative processes.
The significance of acanthocytosis in PKAN, in addition to the other NA syndromes, remains poorly understood. As the patient groups for the various NBIA syndromes becoming increasingly organized, the connection between the two groups of disorders may soon be re-investigated with systematic exploration of blood smears for acanthocytes. Plans are underway to continue this fruitful collaboration, which has benefited both the NBIA and the NA fields, at a meeting in 2016, most likely in North America.