- Project leader: Professor M Thoresen MD PhD - Clinical Science at South Bristol, St Michael's Hospital, Bristol
- Project team: Professor A Whitelaw MD, Professor S Love FRCPath
- Other locations: Department of Neonatal Medicine, University of Bristol, Southmead Hospital,
- Duration: 2 years
- Grant: £94,782
- Status: Ongoing research
Water on the brain: towards the first ever drug treatment
Babies who are born very prematurely are at high risk of bleeds to the brain, which can result in hydrocephalus (water on the brain). There are several hundred new cases of hydrocephalus each year in the UK, which often lead to cerebral palsy and life-long health problems. Researchers are searching for the first ever safe, effective drug therapy.
What's the problem and who does it affect?
Very premature babies can develop water on the brain
Improvements in the care of very premature babies mean more babies are surviving. But these tiny babies are still at high risk of serious illness. Bleeding in the brain, because the blood vessels are weak in infants born too early, is all too common and can cause permanent problems.
A major complication of a large bleed is hydrocephalus, also known as 'water on the brain'. Blood clots block the flow, and hinder the drainage, of the watery fluid that normally circulates within and around the brain. Too much water is left inside the brain, and the baby's head will become enlarged, causing an increased pressure, which may damage the brain.1
A safe, effective treatment remains elusive
There is no cure for water on the brain. About two-thirds of babies with water on the brain sadly go on to develop either cerebral palsy, cognitive disabilities, epilepsy, or become blind or deaf. 2,3
Even babies that escape these complications, face the prospect of a lifetime of dependence on a shunt - a special tube inserted surgically to drain surplus fluid from the brain to the abdomen. Unfortunately, shunts themselves can cause complications, such as infection or blockage, leading to increased pressure and further brain injury.
What is the project trying to achieve?
Testing two candidate drug treatments
The researchers will test two different drugs to see if they have potential for treating water on the brain.
Researchers chose these drugs because they target a substance, called transforming growth factor beta, which seems to be involved in the disease process. Babies who develop water on the brain following a bleed have abnormally high levels of this substance in the fluid around their brain, and the higher the level, the more likely they are to need a shunt.
The research team will test whether the two drugs seem effective in the laboratory, using a technique developed with support from a previous grant from Action Medical Research.
What are the researchers' credentials?
Professor Marianne Thoresen is a leading expert in developing ways to protect the newborn brain against injury. She led pioneering research that showed that cooling babies after they've experienced a lack of oxygen could protect the brain and improve outcomes. This is the first ever treatment shown to work.
Professor Thoresen is both a scientist and a clinical doctor looking after sick newborn babies. She draws on her expertise in both fields to develop ways to study human disease in the laboratory, and is known worldwide for this work.
The research team has all the expertise needed to carry out this project. They are well equipped - their lab has just been enlarged and refurbished - and they work in close collaboration with clinicians who treat babies with water on the brain on a daily basis.
Who stands to benefit from this research and how?
Future plans for trials in babies
If the drugs work in the laboratory, then the researchers plan clinical trials in premature babies who have developed water on the brain after a bleed. There are also more substances to try out if neither of the two suggested drugs turns out to be effective. From the point of view of their potential safety, one drug is a substance that occurs naturally in humans and the other has been used successfully for many years to treat a variety of illnesses in adults.
It is, however, exceedingly important to try out new interventions in the laboratory before entering clinical trials. Previously, adequate models were not developed and outcome was actually worse in the treated group as compared with standard treatment.4
The team hopes their work will ultimately lead to the first ever safe, non-surgical treatment for water on the brain. They hope such a treatment would mean fewer babies need surgery to insert shunts and fewer babies go on to develop cerebral palsy. Many babies could benefit - around 380 premature babies develop water on the brain each year and around 180 have a shunt inserted.1,2,3
Adults could benefit too
Adults might even benefit, as well as babies, as water on the brain can also develop in adulthood following a subarachnoid bleed in the brain.
Footnotes
1. Whitelaw A, Cherian S, Thoresen M, Pople I. Posthaemorrhagic ventricular dilatation: new mechanisms and new treatment. Acta Paediatr Suppl 2004 Feb;93(444):11-4.
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2. Murphy BP, Inder TE, Rooks V, Taylor GA, Anderson NJ, Mogridge N, Horwood LJ, Volpe JJ. Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. Arch Dis Child Fetal Neonatal Ed. 2002 Jul;87(1):F37-41.
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3. de Vries LS, Liem KD, van Dijk K, Smit BJ, Sie L, Rademaker KJ, Gavilanes AW; Dutch Working Group of Neonatal Neurology. Early versus late treatment of posthaemorrhagic ventricular dilatation: results of a retrospective study from five neonatal intensive care units in The Netherlands. Acta Paediatr 2002;91(2):212-7.
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4. International randomised controlled trial of acetazolamide and furosemide in posthaemorrhagic ventricular dilatation in infancy. International PHVD Drug Trial Group. Lancet 1998 Aug 8;352(9126):433-40.
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