The Movement Disorder Society

MDS 19th International Congress of Parkinson's Disease and Movement Disorders. Volume 30, June 2015 Abstract, Volume 30,
June 2015 Abstract Supplement

The International Parkinson and Movement Disorder 2015
San Diego, California, USA June 14-18, 2015.


Systemic plasma biomarkers as a tool to help assess the efficacy of NBIA clinical trials; results from a pilot trial of deferiprone chelation to treat a case of PARK14 Parkinsonism/PLA2G6 associated neurodegeneration (PLAN)

Minkley,  M., Praschberger,  M., Jackson,  A., Smith,  D., Sweeters,  N., Borchers,  C., Vichinsky,  E., Macleod,  P., Walter,  P.

Victoria, BC, Canada

Objective:

Systemic plasma biomarkers were used as a tool to determine the efficacy of deferiprone in a pilot study of iron chelation therapy in a patient with PARK14/PLAN.

Background:

Current understanding of systemic biomarkers in Parkinson's disease and Neurodegeneration with Brain Iron Accumulation (NBIA) disorders is limited. These markers can potentially be used as diagnostic tools to assess disease severity and evaluate the outcome of clinical trials; including unique therapies such as deferiprone, an iron chelator, which, based on preliminary trials, may mobilize accumulated brain iron and offer symptomatic improvement to patients.

Methods:

The PLAN patient is a 29 year old male with a heterozygous mutation in the PLA2G6 gene that was treated following a 5 year history of progressive, early‐onset Parkinsonism. Samples were studied at baseline and over the course of 37 weeks of deferiprone treatment (30mg/kg). C‐Reactive Protein (CRP), as well as a hematological panel were measured using laboratory services. Inflammation (IL‐6) was measured using ELISA. Oxidative stress markers malondialdehyde (MDA) and 4‐hydroxynonenal (4‐HNE) were measured using an N‐methyl‐2‐phenylindole based assay. Plasma proteins were measured using multiplex multiple reaction monitoring proteomics.

Results:

The patient had increased systemic inflammation at baseline, including plasma IL‐6 that was 4 times higher than control, an elevated CRP of 4.0 ug/ml and Lipocalin‐2 (NGAL) was increased by 62%. The patient also had a 30% increase in systemic oxidative stress (MDA and 4‐HNE). Over the course of 37 weeks of deferiprone treatment IL‐6 was reduced by 13%, CRP returned to the normal range (2.0ug/ml) and MDA was reduced by 16%, however, in 6 months of therapy there was no change in neurodegenerative symptoms. Additional biomarker studies in NBIA patients are ongoing.

Conclusions:

During deferiprone therapy, biomarker analysis revealed a reduction in oxidative stress and inflammation in the absence of any significant change in the clinical presentation of the disease. Based on previous trials, we suggest that longer treatment régimes (greater than 37 weeks) and earlier intervention with therapy may be two important factors in the success of deferiprone in improving neurodegenerative symptoms.

To cite this abstract, please use the following information:
Minkley, M., Praschberger, M., Jackson, A., Smith, D., Sweeters, N., Borchers, C., Vichinsky, E., Macleod, P., Walter, P.; Systemic plasma biomarkers as a tool to help assess the efficacy of NBIA clinical trials; results from a pilot trial of deferiprone chelation to treat a case of PARK14 Parkinsonism/PLA2G6 associated neurodegeneration (PLAN) [abstract]. Movement Disorders 2015;30 Suppl 1 :271