New therapies for neurodegenerative disorder

NBIA is a group of rare disorders characterised by high levels of iron accumulation in the brain. The most frequent form of NBIA is Pantothenate Kinase-Associated Neurodegeneration (PKAN). Symptoms in PKAN and most other NBIA forms present early in childhood, and the diseases progress to life-long disability and often to early death. As currently no cure is available to reverse or halt NBIA.

Iron accumulation and the enzyme defect in PKAN could in principle be amenable to drug-based treatment but scarcity and regional dispersal of patients have rendered research fragmented, precluding conduct of randomised clinical trials. At the core of the EU-funded TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration) project is a clinical phase 2/3 trial to test safety and efficacy of the iron-chelating drug deferiprone in a cohort of 90 PKAN patients from Europe and US, a drug that thus far is licensed only for other indications (thalassaemia). Despite of the rarity of PKAN with a prevalence of about 1 in 1 million, TIRCON has succeeded in fully recruiting this trial, which will be completed in autumn 2016.

In addition, TIRCON's now well established internationally harmonised patient registry comprises more than 230 patients, giving access to their pseudonymised data and biomaterial samples. This sample collection is used for genomic, proteomic, transcriptomic and metabolomic analyses to better understand causes and aetiology, and to identify biomarkers of NBIA.

The consortium is also active in evaluating the potency of other candidate therapies such as pantethine and its derivatives in pre-clinical animal models. Preliminary results show improvement of locomotor defects in NBIA animal models upon treatment with pantethine, which underscores its potential clinical use.

TIRCON infrastructure and tools as well as the highly collaborative new NBIA community will facilitate future research in NBIA, for example to identify biomarkers that can serve diagnosis, prognosis, and the monitoring of disease course and treatment effects. The interventional study at the core is anticipated to improve the therapeutic options for this progressive, highly disabling and life-threatening disease.