A short-term trial of butyrate to stimulate fetal-globin-gene expression in the β-globin disorders

Susan P. Perrine, Gordon D. Ginder, Douglas V. Faller, George J Dover, Tohru Ikuta, H. Ewa Witkowska, Shi Ping Cai, Elliott P. Vichinsky, Nancy F. Olivieri

Research output: Contribution to journalArticle

Abstract

Background. Fetal-globin (γ-globin) chains inhibit the polymerization of hemoglobin S (sickle hemoglobin) and can functionally substitute for the β-globin chains that are defective or absent in patients with the β-thalassemias. Identifying safe mechanisms to stimulate fetal-hemoglobin production is therefore of great interest. Previous studies have shown that administering butyrate selectively stimulates the promoter of the human fetal-globin gene and leads to increases in γ-globin-gene expression in the developing fetus, cultured cells, and animal models. Methods. To determine whether butyrate can stimulate fetal-globin production in humans, we treated three patients (3 to 13 years old) with sickle cell anemia and three patients (7 to 27 years old) with β-thalassemia syndromes with a short course of intravenous infusions of arginine butyrate. The drug was infused continuously for either two or three weeks; the initial dose was 500 mg per kilogram of body weight per day. Globin-chain ratios, proportions of reticulocytes producing hemoglobin F (F reticulocytes), and levels of γ-globin messenger RNA (mRNA) were determined before and during treatment. Results. In all six patients, fetal-globin synthesis increased by 6 to 45 percent above pretreatment levels (P

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalNew England Journal of Medicine
Volume328
Issue number2
StatePublished - Jan 14 1993

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Globins
Butyrates
Gene Expression
Sickle Hemoglobin
Fetal Hemoglobin
Thalassemia
Reticulocytes
Sickle Cell Anemia
Intravenous Infusions
Polymerization
Cultured Cells
Fetus
Animal Models
Body Weight
Messenger RNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Perrine, S. P., Ginder, G. D., Faller, D. V., Dover, G. J., Ikuta, T., Witkowska, H. E., ... Olivieri, N. F. (1993). A short-term trial of butyrate to stimulate fetal-globin-gene expression in the β-globin disorders. New England Journal of Medicine, 328(2), 81-86.

A short-term trial of butyrate to stimulate fetal-globin-gene expression in the β-globin disorders. / Perrine, Susan P.; Ginder, Gordon D.; Faller, Douglas V.; Dover, George J; Ikuta, Tohru; Witkowska, H. Ewa; Cai, Shi Ping; Vichinsky, Elliott P.; Olivieri, Nancy F.

In: New England Journal of Medicine, Vol. 328, No. 2, 14.01.1993, p. 81-86.

Research output: Contribution to journalArticle

Perrine, SP, Ginder, GD, Faller, DV, Dover, GJ, Ikuta, T, Witkowska, HE, Cai, SP, Vichinsky, EP & Olivieri, NF 1993, 'A short-term trial of butyrate to stimulate fetal-globin-gene expression in the β-globin disorders', New England Journal of Medicine, vol. 328, no. 2, pp. 81-86.
Perrine, Susan P. ; Ginder, Gordon D. ; Faller, Douglas V. ; Dover, George J ; Ikuta, Tohru ; Witkowska, H. Ewa ; Cai, Shi Ping ; Vichinsky, Elliott P. ; Olivieri, Nancy F. / A short-term trial of butyrate to stimulate fetal-globin-gene expression in the β-globin disorders. In: New England Journal of Medicine. 1993 ; Vol. 328, No. 2. pp. 81-86.
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