Intractable & Rare Diseases Research
Online ISSN : 2186-361X
Print ISSN : 2186-3644
ISSN-L : 2186-3644
Original Article
Rare and intractable fibrodysplasia ossificans progressiva shows different PBMC phenotype possibly modulated by ascorbic acid and propranolol treatment
Deborah Ribeiro NascimentoSuzana Lopes Bomfim BalaniucDurval Batista PalharesAdam UnderwoodMarilene Garcia PalharesFabiana AlvesFrancisco Oliveira VieiraElaine Maria Souza-FagundesLiane De Rosso GiulianiPaula Cristhina Niz XavierHelen Lima Del PuertoRobson Augusto Souza SantosAmy MilstedJose Mauro BrumIandara Schettert SilvaAlmir Sousa Martins
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2021 Volume 10 Issue 3 Pages 179-189


Fibrodysplasia Ossificans Progressiva (FOP) is a rare congenital intractable disease associated with a mutation in ACVR1 gene, characterized by skeleton malformations. Ascorbic acid (AA) and propranolol (PP) in combination is reported to minimize flare-ups in patients. FOP leukocyte phenotype may possibly be modulated by AA and PP treatment. In this study, expression of 22 potential target genes was analyzed by RT-PCR in peripheral blood mononuclear cells culture (PBMC) from FOP patients and controls to determine effectiveness of the combination therapy. PBMC were treated with AA, PP and AA+PP combination. Basal expression of 12 of the 22 genes in FOP PBMC was statistically different from controls. ACVR1, ADCY2, ADCY9 and COL3 were downregulated while COL1 was upregulated. ADRB1, ADRB2, RUNX2, TNF-α and ACTB, were all overexpressed in FOP PBMC. In control, AA upregulated COL1, SVCT1, ACTB, AGTR2 and downregulated ADCY2. In FOP cells, AA upregulated ACVR1, BMP4, COL1, COL3, TNF-α, ADCY2, ADCY9, AGTR2 and MAS, while downregulated ADBR2, RUNX2, ADCY1, SVCT1 and ACTB. PP increased ADBR1 and decreased RUNX2, TNF-α, AGTR1, ACTB and CHRNA7 genes in treated control PBMC compared to untreated. PP upregulated ADBR1, ADBR2 and MAS, and downregulated TNF-α and ACTB in treated FOP PBMC versus untreated. AA+PP augmented ADRB1 and ADRB2 expressions in control PBMC. In FOP PBMC, AA+PP augmented ACVR1, COL1, COL3, ADBR1, AGTR2 and MAS expression and downregulated ADBR2, RUNX2, ACTB and MRGD. These data show distinct gene expression modulation in leukocytes from FOP patients when treated with AA and or PP.

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© 2021 International Research and Cooperation Association for Bio & Socio-Sciences Advancement
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