Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of rare hereditary neurodegenerative disorders characterized by high levels of brain iron. The most common form is pantothenate kinase-associated neurodegeneration (PKAN). Classic PKAN and most other NBIA cases are characterised by early childhood onset and rapid progression. Currently, there is no proven therapy to halt or reverse PKAN or any other NBIA. This is especially unfortunate as both the iron accumulation in NBIA and the biochemical defect in PKAN are predicted to be amenable to drug-based treatment. Thus, the current absence of clinical trials is not due to lack of therapeutic options but to rarity of the disease, lack of patient registries and fragmentation of therapeutic research worldwide. For example, the iron-chelating drug deferiprone has been administered to PKAN patients on an individual basis or in pilot trials, both precluding firm conclusions about its efficacy. With TIRCON, we will address this urgent and unmet need for NBIA/PKAN therapy with an ambitious and highly collaborative plan that leverages worldwide expertise. We propose a large investigator-driven randomized clinical trial of deferiprone in PKAN, bringing together leading centres and patient advocacy groups from Europe and the US to reach the required patient cohort size.
In addition, together with a European SME, we propose to pursue preclinical development of pantethine and its derivatives which have shown promising efficacy in a Drosophila PKAN model. To facilitate future research, we will develop a harmonized patient registry and biomaterial bank to allow for natural history studies and biomarker development, two critical needs in NBIA research. TIRCON partners, apart from their unique clinical and basic science expertise in NBIA, have longstanding experience in investigator-driven and industry-driven randomized clinical trials. Importantly, they have been closely collaborating in recent years.