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.


Using proteomics to assess potential biomarkers of systemic iron trafficking, inflammation and oxidative stress in a patient with PLA2G6 associated neurodegeneration (PLAN) being treated with deferiprone

Praschberger,  M., Minkley,  M., Jackson,  A., Smith,  D., Borchers,  C., Vichinsky,  E., MacLeod,  P., Walter,  P.B.

Vienna, Austria

Objective:

We used Multiplex multiple reaction monitoring (MRM) proteomics to investigate a patient with PLA2G6 associated neurodegeneration (PLAN) being treated with Deferiprone. The investigation focused on the patient's systemic state of iron trafficking and oxidative and inflammatory stress before and during Deferiprone treatment. Long-term goals include investigation of the systemic state in other neurodegeneration with brain iron accumulation (NBIA) diseases.

Background:

MRM is a tandem mass spectrometry technique that has the ability to analyze specific proteins within a complex background; a necessity in biological samples. A known concentration of SIS peptides corresponding to proteins of interest is run with each sample to quantify the endogenous proteins of interest. MRM has been shown to be a rapid and highly specific method to measure multiple blood plasma proteins from patients. NBIA disorders show signs of iron accumulation and oxidative stress in the brain. Deferiprone, an orally active iron chelator, is an emerging therapy for the treatment of brain iron accumulation. Preliminary studies indicate Deferiprone may be able to mobilize accumulated brain iron and offer symptomatic improvement to patients.

Methods:

Baseline plasma samples were collected from the PLAN patient and a control patient. Additional plasma samples were collected every 3 months over the course of the Deferiprone treatment; 2000mg/day, 30mg/kg. A panel of proteins were analyzed; including markers involved in iron metabolism (eg. transferrin and haptoglobin), oxidative stress (eg. Glutathione peroxidase) and inflammation (eg. Lipocalin-2). All samples were run on an Agilent 6490 and analyzed as previously described.

Results:

Preliminary MRM analysis showed increased levels of lipocalin-2, glutathione peroxidase and ceruloplasmin in the PLAN patient. Iron trafficking proteins, transferrin, haptoglobin and hemopexin showed a response to chelator; they were increased during Deferiprone treatment chelation and decreased when chelator was removed.

Conclusions:

The PLA2G6 patient appears to have elevated systemic markers of oxidative and inflammatory stress. Increased levels of these systemic markers in PLAN suggests their potential use as biomarkers of disease progression. Additional MRM analysis of patient samples is ongoing.

To cite this abstract, please use the following information:
Praschberger, M., Minkley, M., Jackson, A., Smith, D., Borchers, C., Vichinsky, E., MacLeod, P., Walter, P.B.; Using proteomics to assess potential biomarkers of systemic iron trafficking, inflammation and oxidative stress in a patient with PLA2G6 associated neurodegeneration (PLAN) being treated with deferiprone [abstract]. Movement Disorders 2014;29 Suppl 1 :76