The Movement Disorder Society

MDS 18th International Congress of Parkinson's Disease and Movement Disorders, Volume 29,
June 2014 Abstract Supplement

Movement Disorders 2014
Stockholm, Sweden June 8-12, 2014.


A pilot investigation of systemic iron trafficking, oxidative stress and inflammation in a case of PLA2G6 associated (PARK14) neurodegeneration with brain iron accumulation (NBIA) undergoing deferiprone treatment

Minkley,  M., Praschberger,  M., Jackson,  A., Smith,  D., Borchers,  C., Macleod,  P., Walter,  P.

Victoria, Canada

Objective:

Here we present the results of the investigation and treatment of a patient with PLA2G6 associated NBIA with the chelator Deferiprone as well as the paired treatment of THP-1 macrophages as an in vitro model of the potential in vivo systemic iron dysregulation seen in cases of NBIA.

Background:

The patient is a 28 year old male with a four year clinical history of Parkinsonism with dystonia and a heterozygous mutation in the PLA2G6 gene(1). Symptoms of PLA2G6 associated NBIA include iron accumulation in the Globus Pallidus. Iron chelation therapy, is an emerging treatment for NBIA. Preliminary studies indicate Deferiprone, an iron chelator, may be able to mobilize accumulated brain iron and offer symptomatic improvement to patients.(2)

Methods:

Deferiprone treatment target dose was 2000mg/day (30mg/kg). Cognitive, motor and behavioural changes, as well as all adverse experiences, experienced by the patient were recorded. THP-1 macrophages and cultured patient and control cells were exposed in vitro to iron overload conditions. Following treatment malondialdehyde (MDA) levels were measured using an NMPI based detection assay. Additionally inflammatory cytokines (IL-6, IL-10, TNFa, TLR-4) and reactive oxygen species were measured by flow cytometry.

Results:

MRI scans confirmed abnormally high iron deposition inside the Globus Pallidus(1). Deferiprone treatment is well tolerated, but the patient's functional status did not change significantly. Initial patient analysis showed increased levels of plasma MDA and CRP. Preliminary in vitro THP-1 investigation showed increased levels of IL-6 and MDA in response to increasing iron treatment.

Conclusions:

The apparent lack of clinical response may be due to the degree of disease progression prior to the initiation of treatment. The patient appears to be undergoing inflammation and increased systemic oxidative stress. THP-1 macrophages showed an in vitro inflammatory response and increased oxidative stress in response to iron overload conditions.

1.Agarwal, P et al. (2012). Imaging striatal dopaminergic function in phospholipase A2 group VI-related parkinsonism. Movement disorders.

2. Mounsey, R., & Teismann, P. (2012). Chelators in the Treatment of Iron Accumulation in Parkinson's disease. Cell Biology.

To cite this abstract, please use the following information:
Minkley, M., Praschberger, M., Jackson, A., Smith, D., Borchers, C., Macleod, P., Walter, P.; A pilot investigation of systemic iron trafficking, oxidative stress and inflammation in a case of PLA2G6 associated (PARK14) neurodegeneration with brain iron accumulation (NBIA) undergoing deferiprone treatment [abstract]. Movement Disorders 2014;29 Suppl 1 :675