Genome Wide Expression Analyses Reveal Potentially Novel Drug Targets in Fibromyalgia

Kim Jones¹, Robert Bennett^2,3 and Sunil Kurian⁴, ¹Rsch & Develop/Mail Code SN OR, Oregon Health Sciences Univ, Portland, OR, ²SN-Office of Research & Development, Oregon Health & Science Univ, Portland, OR, ³Medicine & Nursing, Oregon Health & Science Univ, Portland, OR, ⁴The Scripps Research Institute, La Jolla, CA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: drug therapy, fibromyalgia and genomics, RNA

Session Information

Date: Tuesday, November 10, 2015

Title: Fibromyalgia: Clinical Issues

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Currently there are three drugs approved by the FDA for the treatment of fibromyalgia (FM), and there appears to be a paucity of drugs in development. We recently completed a study with the major aim of discovering biological disease markers that could shed light on the molecular mechanisms that drive FM. Herein we report FM associated genes that are targets of known drugs

Methods:

We analyzed gene expression from the RNA isolated from blood of 70 women with FM and 70 healthy age/gender-matched controls.

Results:

The average FM patient was aged 45.5±7.7 years and had symptoms 17.2±12.2 years. Differentially expressed genes and their known targets of available drugs are displayed below:

Symbol	Gene function	Associated Drug	Disease target
MS4A2	IgE activity	Omalizumab	Allergic asthma
IL3RA	Cytokine receptor	Gm-CSF	Bone marrow stimulation
COL4A6	Type IV subunit	Collagenase	Skin debridement
MUT	Vit B12 metabolism	Cyanocobalamin	Pernicious anemia
NPY2R	Appetite regulation	Peptide YY 3-36	Appetite regulation
CPT1A	Mitochondrial transport	Perhexiline	Angina pectoris
ITGA4	Cell surface adhesion molecule	Natalizumab	Multiple sclerosis
GGPS1	C20-prenylation of proteins	Zoledronic acid	Osteoporosis
CA3	Carbonic anhydrase gene	Thiazide diuretics	Hypertension
VWF	von Willebrand factor gene	Factor 8	Hemophilia
ALDH5A1	Aldehyde dehydrogenase gene	Valproic acid	Anticonvulsant
HRH4	Histamine receptor gene	Triprolidine	Nasal allergies
YES1	Tyrosine kinase gene	Dasatinib	Chronic myeloid leukemia

Conclusion:

Overall, genes associated with immune/inflammatory responses were up-regulated as were genes associated with neuronal development and neurotransmitters. Conversely, genes associated with allergic responses were down-regulated. There were 14 differentially expressed kinase molecules, 21 transcriptional regulators and 21 transporter molecules that have never been previously reported in FM. These represent opportunities for novel drug targets. There were 13 genes differentially expressed in FM that are known targets of already available drugs. These data contribute new targets for the further exploration of both existing drugs and development efforts to identify new candidate therapies based on molecular markers that may underlie FM disease mechanisms.

Disclosure: K. Jones, None; R. Bennett, None; S. Kurian, None.

To cite this abstract in AMA style:

Jones K, Bennett R, Kurian S. Genome Wide Expression Analyses Reveal Potentially Novel Drug Targets in Fibromyalgia [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/genome-wide-expression-analyses-reveal-potentially-novel-drug-targets-in-fibromyalgia/. Accessed .

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