Treat Iron-Related Childhood-Onset Neurodegeneration (TIRCON)-An International Network on Care and Research for Patients With Neurodegeneration With Brain Iron Accumulation (NBIA)

Abstract

In order to improve clinical care, coordinate research activities and raise awareness for the ultra-orphan Neurodegeneration with Brain Iron Accumulation (NBIA) disorders, a group of NBIA clinicians and researchers, industry partners and patient advocacies from six European countries, Canada and the US joined forces in 2010 to set-up the collaborative initiative TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration). As a research project, TIRCON received funding in the 7th Framework Programme (FP7) of the European Union (EU) from 2011 to 2015. After successful and timely completion of the initial FP7 project, funding and donations from industry and patient organizations have sustained the further development of TIRCON's dedicated clinical research infrastructure and its governance architecture, as well as the ongoing efforts undertaken in the NBIA community to establish a network of care. From the beginning, the University Hospital of the Ludwig-Maximilians-University in Munich, Germany has been coordinating the TIRCON initiative. It consists of 8 work packages, of which the first double-blind, placebo-controlled, randomized, multi-site clinical trial in NBIA (deferiprone in PKAN, completed) and a global patient registry and biobank, currently comprising baseline and follow-up data of > 400 NBIA patients have gained particular importance. Here we describe TIRCON's history with all the challenges and achievements in diagnosing and treating NBIA. Today, TIRCON lays the ground for future clinical care and research. In these times, it may also serve as a good example of well-directed governmental funding and fruitful international scientific collaboration.

Keywords: NBIA; TIRCON; clinical network; movement disorder; orphan disease; patient registry.

Conflict of interest statement

TK served as coordinating investigator of the FORT trial; received research funding from Retrophin Inc.; served as coordinating investigator of the deferiprone in PKAN randomized and extension trial; received research funding from ApoPharma Inc.; received support from the European Commission 7th Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984, TIRCON) and from the European Reference Network for Rare Neurological Diseases (ERN-RND), co-funded by the European Commission (ERN-RND: 3HP 767231); provided consulting services to CoA Therapeutics and TM3 Therapeutics; received travel support from ApoPharma Inc. BB provided consulting services to Retrophin Inc. and ApoPharma Inc. IK received travel support from ApoPharma Inc. FG received support from the European Commission 7th Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No.277984, TIRCON). AK received support from the European Commission 7th Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984, TIRCON); received travel support from Retrophin Inc.

Copyright © 2021 Karin, Büchner, Gauzy, Klucken and Klopstock.

Figures

Figure 1

Overview of TIRCON work packages.

Figure 2

TIRCON centers: T / F, initially involved TIRCON partners, full clinical centers and their respective countries; A, centers/countries, joined the network after the project start; P, patient organizations.

Figure 3

Distribution of NBIA subtypes in the TIRCON patient registry (PKAN, Pantothenate Kinase-Associated Neurodegeneration; MPAN, Mitochondrial-membrane Protein-Associated Neurodegeneration; PLAN, PLA2G6-Associated Neurodegeneration; BPAN, Beta-propeller Protein-Associated Neurodegeneration; FAHN, Fatty Acid Hydroxylase-Associated Neurodegeneration).

Figure 4

TIRCON registry—baseline (black) and follow-up visits (different colors used, depending on the total number of follow-up visits) over time.

Figure 5

Major NBIA events since 2012—TIRCON meetings, scientific symposia, family conferences.