Sparks is one of the few charities that funds research into the wide range of conditions that can affect babies and children.

We support vital medical research that will:

• Increase the life expectancy of new born babies
• Reduce the health risks for babies born prematurely
• Combat common conditions such as spina bifida and cerebral palsy
• Develop more effective treatments for conditions affecting babies and young children

Currently Sparks is funding more than 30 research projects. 16 new research grants were awarded in 2007 to hospitals and universities throughout the UK with a total value of £1,910,887.

9 medical projects were awarded in January 2007

Total Funding: £1,267,190

 

HOW MANY CHILDREN ARE GENETICALLY SUSCEPTIBLE TO ANTIBIOTIC-ASSOCIATED HEARING LOSS?

UCL Institute of Child Health, London - £11,637 over 12 months

Aminoglycosides are powerful antibiotics used in hospitals for serious infections. Some individuals are particularly at risk of this type of hearing loss because they have inherited a mutation which makes them genetically susceptible. This was thought to be a rare mutation in the general population but larger studies have never been carried out. Moreover, recent small scale studies suggest that it may be much more common than was previously thought. Sparks funding will enable researchers to determine how many children are susceptible, and apply genetic testing before aminoglycosides treatment.

IMPROVING THE EFFICIENCY OF GENE THERAPY FOR CYSTIC FIBROSIS

UCL Institute of Child Health, London - £192,171 over 36 months

Cystic Fibrosis is the UK’s most common, life-threatening, inherited disease, affecting over 7, 500 people of whom half are under 15 years old. Cystic fibrosis affects vital organs in the body, especially the lungs, clogging them with sticky mucus, which makes it difficult to breathe.

1 in 25 people carry the human gene associated with cystic fibrosis. Gene therapy for cystic fibrosis involves inserting a normal version of the cystic fibrosis gene into the cells that line the airways of the lung. The goal of this Sparks funded research is to develop more efficient methods for delivery of the gene, in an aerosolised formulation by inhalation to the airways of the lungs.

PREVENTING CHRONIC PSEUDOMONAS LUNG INFECTION IN CHILDREN WITH CYSTIC FIBROSIS

Paediatric Cystic Fibrosis Centre, Southampton University Hospitals - £179,056 over 24 months

Despite current best efforts, the lungs of most children with cystic fibrosis become chronically infected with bacteria called Pseudomonas aeruginosa. Those infected by Pseudomonas have severe illnesses and die earlier. Researchers think that the early events causing chronic infection with Pseudomonas occur at the time of respiratory tract infection with viruses.

This original Sparks funded interventional study will use conventional and molecular microbial techniques to discover whether giving antibiotics against Pseudomonas at times of viral infection successfully keeps children’s airways clear of these bacteria. If proven, this will directly result in significant changes in current best practice to prevent death and illness.

IDENTIFYING GENES FOR SPINA BIFIDA IN HUMANS

UCL Institute of Child Health, London - £124,806 over 24 months

Spina bifida is a crippling birth defect that affects around 17,000 babies annually, worldwide. Although faulty genes are involved, researchers still do not know which genes are crucial.

Previous Sparks funding has shown that the affected human fetus have faulty “planar cell polarity” genes. To confirm these findings, a research team led by Professor Andrew Copp, Director of the Institute of Child Health, plan to study the genes in more detail. The research team will also analyse the gene mutations in cells, to show whether they are a likely cause of spina bifida. This work could lead to improved prenatal diagnosis, genetic counselling and hopes to help focus clinical treatment for spina bifida within five years.

INFLUENCE OF INSULIN ON THE HORMONAL RESPONSE TO SEVERE ILLNESS

University Department of Paediatrics, Addenbrookes Hospital, Cambridge - £33,154 over 18 months

The body deals with severe illness by mounting a hormonal stress response. This response is essential for survival but it can make matters worse, particularly in severe illness. In adults, modulating this response with insulin (to reduce hyperglycaemia) reduces mortality.

A Sparks funded research team aim to better understand this response in severely ill children, and assess how insulin modulates it. The Cambridge-based researchers will study a control (no insulin) and an intervention group (receiving insulin), by monitoring glucose level and hormonal profile. The control group will reveal the child’s hormonal response to severe illness and the insulin group will reveal how insulin modulates it.

The early detection of childhood leukaemia

Institute of Biomedical Research, University of Birmingham Medical School - £159,729 over 36 months

Around 1 in 200 of all cancers occur in children under 15 years.

Researchers have recently demonstrated that specific genes are inactivated in leukaemia by a mechanism that is reversible in a laboratory setting by treating cancer cell lines with specific drugs. Some of these drugs are also undergoing clinical trials in patients with haematological malignancies.

Researchers aim to understand the biology of these and associated genes in relation to leukaemia development and to understand in more detail the role these genes play in development of cancer. This research will allow doctors and researchers to better understand the pathogenesis of cancer for future prevention, diagnosis and the development of novel treatment regimes for cancer patients.

The world’s biggest clubfoot research project

EXPLORING CAUSES OF CLUBFOOT IN EUROPE AND THE PACIFIC

Medical Genetics Laboratories, Aberdeen University - £157,486 over 36 months

Congenital talipes equinovarus also known as clubfoot is a common inborn lower leg problem of uncertain cause. Previous Sparks funding has enabled researchers to establish a DNA and information resource from more than 850 families in the UK, Netherlands, and Vanuatu—making this the largest such study in the world. This resource together with the team’s expertise and recent advances in genetics and epidemiology puts them in a unique position to make discoveries that will lead to improved treatments for clubfoot and possibly prevention.

With Sparks support, the dedicated Aberdeen-based research team will now investigate the role of a specific gene that samples from Vanuatu has highlighted as a possible cause of clubfoot; parental smoking and genes involved in how the body processes tobacco toxins; and pregnancy-related risk factors.

GREEN TEA AND RED PEPPER EXTRACTS FOR THE TREATMENT OF NEUROBLASTOMA

UCL Institute of Child Health, London - £161,536 over 36 months

Green tea catechins and red pepper capsaicin are natural compounds that have been shown to suppress the growth of cancer cells. Researchers have recently found that a combination of catechins and capsaicin is highly toxic to neuroblastoma cells, whereas it is almost without effect in normal cells. Sparks funding will enable researchers to use a combination of green tea catechins and red pepper capsaicin and further assess their effects. Using safe, natural compounds for the treatment of neuroblastoma could eliminate chemotherapy-induced side effects and give further hope for a better quality of life to young cancer survivors.

 

3 MEDICAL RESEARCH PROJECTS AWARDED IN JUNE 2007

TOTAL FUNDING £712,002

 

GENETIC CLUES TO SEVERE GROWTH RESTRICTION IN BABIES

UCL Institute of Child Health, London - £162,782 over 30 months

Intrauterine growth restriction (IUGR) leads to 400 perinatal deaths and affects thousands of babies born in the UK each year. Imprinted genes play an important role in fetal growth and are only active when they are inherited from the mother or father. Understanding the molecular mechanisms for growth in the womb will lead to prevention or therapy for IUGR. Researchers have shown that the imprinted gene, PHLDA2 is significantly higher in the placenta of small babies.

Sparks researchers will test if PHLDA2 is a marker for IUGR by measuring it in the placenta throughout pregnancy compared to birth weight. This research will determine If imprinted genes can act as diagnostic markers to predict growth problems in the womb, helping around 36,000 babies who are born small for their gestational age.

PREVENTING INFECTION IN NEWBORN BABIES

UCL Institute of Child Health, London - £162,374 over 30 months

Every year over 1000 babies born in the UK require major surgery. Afterwards many infants require drip feeding because their gut does not work. During the drip feeding, their capacity to fight infections is impaired. Infections can prolong their stay in hospital, damage the liver and have potentially serious consequences. The nutrient glutamine, a building block of protein, abundant in the human body and found in large quantities of breast milk, may enhance an infant’s capacity to fight infections. Sparks researchers will determine whether giving glutamine during the drip feeding, is beneficial to these infants by reducing their exposure to nasty bugs and by improving their capacity to fight infection.

FINDING THE TRIGGER TO NEONATAL BRAIN INJURY

University College, London - £200,276 over 3 years

Babies born more than 8 weeks early are particularly vulnerable to brain injury with up to 20-30% having some neurological deficit in later life. Exposure to oxygen deprivation and/or bacterial infection around the time of birth is thought to trigger an intracellular response that will lead to loss of brain connections and disability. Researchers believe the Mitogen-Activated Protein Kinase (MAPK) and Extracellular signal-Regulated Kinase (ERK) group of molecules play a key role in mediating brain damage following oxygen deprivation and/or exposure to bacterial products, and with Sparks funding now aim to determine their role in this dysfunction. This research will help improve management of mothers and babies to reduce the risk of long-term brain damage.

Sparks largest research grant

IS MILD POST-HYPOXIC HYPOTHERMIA COMBINED WITH XENON NEUROPROTECTIVE?

St Michael’s Hospital, University of Bristol - £591,914 over 52 months

3 in every 1000 babies born in the UK will have their brain damaged by a momentary shortage of oxygen and blood supply during labour, this can lead to disabling conditions such as cerebral palsy, mental retardation and epilepsy.

Cooling newborn babies that have suffered a lack of oxygen around time of birth down from 37-34°C for three days has been shown to help prevent brain injury and increase survival with reduced disability. This treatment only helps one in six infants; therefore a more effective treatment is needed.

A further two Sparks awards totalling £434,185 were made in January 2007 and June 2007 to Professor Marianne Thoresen to continue her original Sparks research into brain cooling as an effective treatment against brain injury in babies.

Previous research funded by Sparks has contributed to the development of a “cooling cap” that can help to prevent brain damage when babies have suffered a lack of oxygen at birth. While this treatment has made a positive difference, it is not effective in all cases.

Professor Thoresen and her Bristol-based research team are currently investigating whether the addition of minute doses of xenon gas (an inert non-toxic gas found in nature and with known anaesthetic and sedative properties) to the ventilated air administered to babies undergoing total brain cooling will improve the outcome for those babies who have suffered brain injury significantly more than either ventilation with Xenon gas or cooling itself.

A NEW APPROACH TO TREATMENT FOR NEUROBLASTOMA

Birmingham University - £63,370 over 18 months

Neuroblastoma is a very aggressive cancer that affects only children. This disease is due to abnormally developing nerve cells in babies and young children and is the leading cause of cancer deaths in 1 to 5 year olds. SPARKS is at the forefront of cutting edge research into neuroblastoma and this summer awarded two grants funding research into this devastating disease. The galectin-1 gene is thought to play an important role in the development of very aggressive forms of neuroblastoma which can spread to the bone marrow and other sites. SPARKS researchers will investigate in more detail this relationship to discover if it is possible to block the effects of galectin-1. If successful, this research could help doctors radically improve the effectiveness of treatment techniques.

OPTIMISATION OF T CELL RECEPTOR GENE THERAPY OF PAEDIATRIC CANCERS

Institute of Child Health, London - £169,832 over three years

In this SPARKS funded study, gene therapy will be combined with immunotherapy for the specific treatment of paediatric cancers. The overexpression of proteins PAX3 and MYCN is essential for tumour survival and seen in a number of aggressive conditions including neuroblastoma and rhabdomyosarcoma. These proteins not expressed on normal tissues. Optimisation of methodology allowing receptors that recognize PAX3 and MYCN to be inserted into the killer cells (T cells) of the patient’s blood is being undertaken. Genetically altered T cells can then be transferred back into the patient and should detect and specifically kill tumours.

FETAL INFLAMMATORY RESPONSE AND BACTERIAL INFECTION

University College London - £123,477 over two years

Babies born more than 8 weeks early are particularly vulnerable to brain injury with as many as 20 - 30% prone to some neurological problems in later life. Researchers suspect that the reason why some babies are at risk, but not others, is that they may have been exposed to bacterial infection in the womb which is thought to trigger an inflammatory response which can lead to brain damage. SPARKS funding will enable researchers to investigate this further and discover why some premature babies develop long-term complications such as brain and lung injury.

THE EFFECT OF SURGICALLY MOVING THE UPPER JAW ON SPEECH

Great Ormond Street Hospital, London - £86,134 over three years

One in 600 - 700 babies in the UK are born with a cleft of the lip and/or palate. Currently there is no defined way to predict which patients will be at risk of deterioration in speech before surgery. In this SPARKS funded study, researchers will employ a range of speech evaluation techniques with long-term follow-up to provide future patients who seek this surgery with more accurate and objective information regarding the potential risks on speech.

DETECTING AND MONITORING TREATMENT IN GENETIC DEFECTS OF ENERGY METABOLISM

University of Newcastle upon Tyne - £75,333 over two years

Mitochondria are the main energy producers of the cell and contain their own circular molecule of DNA. 1 in 3500 children and adults are affected by genetic mitochondrial abnormalities causing a wide range of neurological disorders. These disorders are difficult to diagnose as they are often undetectable in blood and there are no current cures.

Research in this area has recently shown that cells excreted in the urine contain high levels of these mitochondrial mutations and may offer an alternative test to muscle biopsy. SPARKS funded researchers aim to understand why this happens, develop these tests and use them to monitor treatment strategies.

EVALUATION OF IMMUNE RESPONSE TO CANDIDATE PNEUMOCOCCAL PROTEIN VACCINES IN CHILDREN

Bristol University - £76,500 over 18 months

Pneumococcus causes pneumonia and meningitis and kills approximately one million young children each year worldwide. Current vaccines have limited coverage, are very expensive and require multiple doses by injection. Many alternative cheaper, easier vaccines are under study but probably only one or two will complete development. A new vaccine could help prevent 100 - 200 deaths in the UK. Sparks is funding the research team based at Bristol University who will compare children’s immune responses to several vaccines. This work will help predict which new vaccines to use in clinical trials in the near future.

GENERATION OF SPECIFIC T-CELLS AS A POSSIBLE NEW MODE OF TREATMENT FOR CHILDHOOD AUTOIMMUNE LIVER DISEASE

King’s College London - £150,265 over three years

Autoimmune hepatitis and autoimmune sclerosing cholangitis are autoimmune liver diseases (AILD) affecting mainly children, whose immune system fails to recognise components of the liver as self and attacks them. The disease is now ten times more common than it was ten years ago.

AILD can be controlled rather than cured; even then the lifelong treatment is not always effective in preventing progression to end-stage liver disease requiring liver transplantation.

Regulatory T-cells present in our immune system, control immune response, are pivotal to preventing self attack by the immune system. These are found to be defective in AILD. Sparks is funding a research team at King’s College London that aims to generate specific T-cells in a laboratory using patients’ blood and liver cell samples and investigate their potential therapeutic use in the treatment for children with AILD, with the eventual aim of using them to halt the disease process.

IS CARDIOLIPIN DEFICIENCY A SIGNIFICANT CAUSE OF MITOCHONDRIAL DISEASE?

University College London Hospital - £88,540 over two years

The generation of energy in every cell of the body is dependent on structures known as mitochondria. If mitochondria are not functioning correctly, this can lead to energy metabolism disorders and disease.

1 in 7,500 children are born with mitochondrial disease. It is the third most common cause of neurological deterioration in childhood and there are currently are no effective treatments for this group of disorders.

Recent research suggests that a lipid (fat) known as cardiolipin may be essential for optimum mitochondrial function and may be deficient in patients with mitochondrial disease.

Sparks funded researchers intend to develop a new reliable diagnostic assay for the routine assessment of cardiolipin in patients and investigate potential treatment regimes targeted at correcting the deficiency with the ultimate aim being to restore normal mitochondrial cell function.

PAIN ASSESSMENT IN VERY PRE-TERM BABIES

University College London Hospital - £21,168 over one years

80,000 babies per year are admitted to neonatal units in the UK, over 15,000 are very premature and may need intensive care until they reach full term or can go home.

Babies in hospital may need to undergo numerous and at times painful procedures, as they are unable to communicate it is difficult to gauge if they have received the right amount of pain relief.

A research team at UCL has observed that facial responses to pain e.g. brow furrowing (part of current facial pain coding scales) occur later than expected in most premature babies. Sparks has approved funding for a project that aims to measure the timings of these responses in babies. The long term aim is to improve the daily care of babies receiving intensive and eventually look at more effective use of analgesia.

DEFECTIVE IMMUNE SYSTEM GENES CAUSE UNCONTROLLED GROWTHS IN CHILDREN’S AIRWAYS

Cardiff University - £142,397 over three years

Recurrent Respiratory Papillomatosis (RRP) is a rare, but potentially fatal disease caused by Papillomavirus infection, in which warts block the breathing passages.

There are approximately 500 children aged between 0 -15 with RRP in the UK. Currently there is no cure for this distressing illness, where infants and children quite literally are unable to breath and have to undergo repeated (sometimes monthly) surgery to remove obstructions leading to a poor quality of life.

A research team at Cardiff University have already identified some genes that are linked with this condition, and shown that patients have weak immune defences against Papillomaviruses.

Sparks will be funding the team as it now aims to confirm whether these children have either missing proteins from part of their immune system and /or whether they produce too much of a control protein which may stop the immune system from removing the virus-infected cells properly. The long term aim of this project is to reduce the need for frequent surgical intervention which in turn would have a dramatic effect on the quality of life for these children.

IS MILD POST-HYPOXIC HYPOTHERMIA COMBINED WITH XENON NEUROPROTECTIVE?

University of Bristol - £149,826 over three years

3 in every 1000 babies born in the UK will have their brain damaged by a momentary shortage of oxygen and blood supply during labour, this can lead to disabling conditions such as cerebral palsy, mental retardation and epilepsy.

Cooling newborn babies down from 37 - 34°C for three days if they have suffered lack of oxygen around the time of birth has been shown to help them survive with reduced disability. This treatment only helps one in six infants; therefore a more effective treatment is needed. This Sparks funded study will investigate whether the combination of body cooling whilst being ventilated with Xenon gas (an inert non-toxic gas found in nature and with known anaesthetic and sedative properties) will be more effective in protecting babies brains from further brain damage significantly more than either breathing Xenon gas or body cooling itself.

USING A PATIENTS OWN IMMUNE CELLS TO TREAT CANCER

Institute of Child Health - £149,886 over three years

Exciting new discoveries have been made recently in cancer research. It now appears possible to use a patient’s own immune cells to treat their cancer. The immune cells are removed from the patient, grown in the laboratory and taught to recognise proteins produced by the cancer cells. These cells are grown in large numbers and can then be injected back into cancer patients. Sparks funded researchers aims to determine conditions for the most efficient production of such immune cells in the laboratory in order to treat common cancers like neuroblastoma, the biggest cancer killer in the under 5’s.

assessing the role of clusterin in neuroblastoma

Institute of Child Health - £146,647 over three years

Neuroblastoma is a very aggressive cancer affecting children and the leading cause of cancer deaths in 1 to 4 year olds. The team at the Institute of Child Health in London is conducting a study into the role of the clusterin gene and how it affects tumour development and survival probability. If successful, this Sparks project will help doctors to predict the chance of survival and improve the effectiveness of treatments.

The use of chemokine receptor inhibitors as a therapeutic intervention for meningococcal "blood poisoning"

University of Sussex - £26,000 over two years

Meningococcal disease is the most common infectious cause of death in children in the UK. Despite treatment with antibiotics, the mortality rate remains at 10% in children who develop septic shock. In this serious condition, an inflammatory response occurs when the receptors in a child’s immune system sense the “poison” from meningococcal bacteria in the blood stream. This Sparks study will test an inhibitor for the chemokine receptor in order to determine its potential use as a treatment for meningococcal septic shock.

can we improve asthma control by monitoring exhaled nitric oxide?

University of Southampton - £95,833 over two years

Asthma is the most common chronic illness affecting children worldwide and is the third leading cause of hospitalization among those under age 15. Doctors are forced to weigh the costs and benefits of using the main treatment for asthma, which is inhaled steroids. Sparks is supporting the team at the University of Southampton who will measure exhaled nitric oxide levels with a simple, child-friendly breathe test. We hope that this study will help them move towards developing a treatment that would require the smallest dose of inhaled steroids possible in order to prevent future asthma attacks.

improving the diagnosis and treatment of children with primary ciliary dyskinesia

University of Leicester - £109,695 over two years

Primary Ciliary Dyskinesia, a condition in which the millions of microscopic hairs used to clear mucus out of the airways or nasal passages do not function properly, can lead to chronic lung and sinus disease. Seventy children are born with PCD each year in the UK. There is currently no prenatal diagnosis for this condition and late or misdiagnosis of symptoms is all too common. The Sparks funded group at the University of Leicester hopes to enhance the accuracy of early diagnosis and explore specific treatments that will help children afflicted by this rare genetic disease.

does amiloride reduce brain damage in newborn infants with asphyxia?

University College London - £129,081 over two years

Two in one thousand babies born prematurely in the UK will have their brain damaged by a momentary shortage of oxygen and blood supply during labour. Damage results when the brain goes from being acidic during asphyxia to alkaline after resuscitation. Sparks is funding this project which looks at the protective effects of amiloride, a new drug that would balance brain pH. If successful this will prevent the brain damage that accounts for so many neurological handicaps in children.

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