Danielle Blemur, Fozia Mir, and Saud Sadiq, MD
Presented at the 68th annual meeting of the American Academy of Neurology, held April 15-21, 2016 in Vancouver, BC, Canada.
To analyze the serum levels of the uremic toxin 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in multiple sclerosis (MS)
patients and healthy controls.
We first found CMPF to be elevated in the CSF of progressive MS patients, using a global metabolomic screening approach. CMPF is a
furan fatty acids metabolite which is excreted into the urine via organic anion transporters. CMPF accumulates at very high concentrations
in the serum of uremic patients. It has also been implicated in the induction of beta cell dysfunction in diabetes and thyroid irregularities.
CMPF is bound to albumin and has been reported to inhibit cellular transport, erythropoiesis and mitochondrial respiration.
Cerebrospinal fluid (CSF) and blood was obtained from healthy controls and MS patients with informed consent under an IRB-approved
protocol. Samples were immediately processed and stored at -80 degree until use. CMPF levels were quantitated using a competitive ELISA
from NovaTein Biologicals, USA. Data obtained was analyzed using Graphpad Prism.
In the current study we sought to validate the metabolomics results in a larger independent cohort of MS patients. Indeed serum CMPF
levels were found to be significantly elevated in the MS patients (n = 183) as compared to the normal healthy controls n = 38) with a p
value of < 0.0001. The increase was more pronounced increase in CMPF levels in primary progressive patients as compared to the relapsing
remitting patient group. Additionally, elevated CMPF levels correlate with disease activity in MS patients. On a cellular level, we have
localized the CMPF transporter - solute carrier family 22 member 8/organic anion transporter 3 (SLC22A8), to the glia and neurons in the
central nervous system.
The results are the first report of increased CMPF levels in MS and clearly warrant further investigation of its role in the pathogenesis of