26 October 2009
Trichostatin A, an agent initially investigated in the laboratory as a possible cancer therapy, has been shown to inhibit contractions in muscle from the uterus and could have a role in preventing premature labour[i],[ii]
. The research, carried out by a team at Newcastle University, was funded by leading children’s charity, Action Medical Research.
Around 50,000 babies are born too early in the UK each year[iii],[iv]
, yet little is known about what causes premature birth or how to prevent it. Premature birth is the biggest single cause of death in infants, and around 1,500 babies die in the UK as a result of this[v],[vi],[vii]
. A variety of drugs are used to reduce the incidence of premature labour, but few are effective and some have serious side effects.
It has been previously shown that protein kinase A (PKA), is involved in controlling the relaxation of the uterus during pregnancy, and that levels of PKA are higher in pregnant woman compared to non-pregnant woman[viii]
and then decrease at the start of labour. Researchers using uterine muscle samples from patients at the Royal Victoria Infirmary, Newcastle showed that the drug, Trichostatin A, increased the levels of a protein subunit of PKA and also inhibited smooth muscle contractions in these tissues1
Professor Nick Europe-Finner, the project leader and Professor of Myometrial Science at Newcastle University, said: “This is an exciting new discovery as we now know that protein kinase A has an important role in controlling relaxation of the uterus during pregnancy. The discovery that Trichostatin A can inhibit contractions, presumably due to its effect on PKA, means that this drug could potentially be used to prevent premature labour, however further laboratory studies are needed to asses the effectiveness of this and similar anti-cancer agents.”
Dr Magdalena Karolczak-Bayatti, Research Fellow, Newcastle University commented: “More laboratory research should help us to determine exactly how Trichostatin A regulates PKA levels and affects uterine muscle contraction. ”
Premature birth can have negative, long-lasting effects on both the mother and the baby. For many women, preterm labour is shocking, frightening and unexpected.
“This project has uncovered some of the molecular pathways that regulate uterine contractions and so could be linked to premature birth. The results showing that Trichostatin A can inhibit contractions in the uterus means it could have a role in preventing premature birth. Finding a new treatment for early labour would be a major step forward,” says Dr Yolande Harley, Deputy Director of Research at Action Medical Research.
There are several factors which can increase a woman’s risk of going into premature labour including age, infection and inflammation. However, often, the first indication of a problem is when a woman arrives at hospital in preterm labour. Many premature babies, particularly those who are born very early, are at risk of developing serious problems, such as cerebral palsy, blindness, deafness and developmental delay.
[i]Moynihan A T. Hehir Mark P. Sharkey AM. Robson S C. et al. Histone deacetylase inhibitors and a functional potent inhibitory effect on human uterine contractility. Am J Obstet Gynecol 2008; 199(2):167.e1-7 [ii]Karolczak-Bayatti M., Loughney AD., Robson SC., Europe-Finner G.N. Epigenetic modulation of the Protein Kinase A RIIa (PRKAR2A) gene by Histone deacetylases 1 and 2 in human smooth muscle cells, JCMM (in press). [iv] Office for National Statistics. Health Statistics Quarterly 35 (Autumn 2007), Table 2.1: http://www.statistics.gov.uk/downloads/theme_health/HSQ35.pdf [v] Office for National Statistics. Health Statistics Quarterly 32, Winter 2006: http://www.statistics.gov.uk/downloads/theme_health/HSQ32.pdf [vi] General Register Office for Scotland. Vital Events Reference Tables 2006. Section 4: Stillbirths and Infant deaths. Table 4.7: http://www.gro-scotland.gov.uk/files1/stats/06t4-7.pdf
7) MacDougal MWJ., Europe-Finner GN. Robson SC., Human Myometrial Quiescence and Activation during Gestation and Parturition Involve Dramatic Changes in Expression and Activity of Particulate Type II (RIIa) Protein Kinase A Holoenzyme (2003) The Journal of Clinical Endocrinology & Metabolism 88(5):2194–2205.
[viii] Ku CY, Word RA, Sanborn BM.Differential expression of protein kinase A, AKAP79, and PP2B in pregnant human myometrial membranes prior to and during labor. J Soc Gynecol Investig. 2005;12(6):421-7 .
Notes to editors:
For further information please contact:
Tola Awogbamiye at Action Medical Research
Tel: 01403 327493/07967 212 839
Dr Magdalena Karolczak/Professor Nick Europe-Finner
Tel: 0191 222 5406
NOTES TO EDITORS:
Action Medical Research is a leading, national medical research charity. For nearly 60 years we have been instrumental in significant medical breakthroughs including the development of the UK polio vaccine and ultrasound scanning in pregnancy. Our research helps babies and children affected by disease and disability. We are currently funding research into serious diseases and conditions, including meningitis, pneumonia, cerebral palsy and inflammatory bowel disease.
Our special appeal, Touching Tiny Lives, funds vital research to help the most vulnerable babies in this country. More research is needed to ensure that all babies, especially babies born prematurely, have the best possible start in life. To date this appeal has raised almost £4m to fund more than 40 high-quality medical research projects into pregnancy complications and premature birth.
Dr Karolczak-Bayatti and Prof Europe-Finner are members of the Uterine Cell Signalling Group (UCSG), which is one of the component units of the newly-formed Institute of Cellular Medicine (ICM, www.ncl.ac.uk/icm), which made a major contribution to Newcastle University being ranked 5th in the UK (of 28) in Unit of Assessment 4 (Hospital-based clinical specialities) in the 2008 RAE. A major theme of ICM is translational research which is a prime aim of the UCSG.