Tweet
Medical X-Press....
Scientists find clue to cause of childhood hydrocephalus
Scientists at The Scripps Research Institute have found what may be a major cause of congenital hydrocephalus, one of the most common neurological disorders of childhood that produces mental debilitation and sometimes death in premature and newborn children.
The research appears in the September 7, 2011, issue of the journal Science Translational Medicine.
Hydrocephalus, which involves excess buildup of cerebrospinal fluid in the brain, affects about 1 in 500 children in the United States. Currently only symptomatic treatment exists—the surgical placement of a shunt to drain away excess fluid. Researchers want to know the condition's causes, so they can figure out how to prevent and treat it. Scientists have known for some time that hydrocephalus was linked to bleeding events in the developing brain, but the reason for that linkage has not been clear.
The new study now suggests that hydrocephalus can be triggered by abnormal levels of lysophosphatidic acid (LPA), a blood-borne lipid that can enter the brain in high concentrations during bleeding events, with profound effects on developing brain cells. The study showed that both blood and LPA itself acted through the same receptor (receptors are proteins to which one or more specific kinds of signaling molecules bind) to produce defects in the brains of developing mice that led to severe hydrocephalus; genetic removal of a specific LPA receptor or pre-treatment with a compound that blocked the receptor largely prevented the condition.
"This provides proof of concept for the medical treatment of this disease," said Jerold Chun, MD, PhD, a professor at Scripps Research and its Dorris Neuroscience Center, and senior author of the new study, "and it also hints that this mechanism involving LPA could be relevant to other neurological conditions associated with altered brain development."
>
Looking Ahead
LPA1-blocking drugs currently are being developed for other conditions including lung fibrosis, and the new finding from Chun's lab may lead biotech or pharmaceutical companies to study their use in hydrocephalus. "If you had an unborn baby who was at risk from an injury to the mother, an infection, or evidence of bleeding then, in principle, you could treat with a short-acting LPA1 blocker to prevent or reduce hydrocephalus," said Chun.
The discovery that excess LPA can wreak havoc in the developing brain could have broader implications as well. Abnormally high concentrations of LPA may be generated by fetal brain cells themselves, also producing abnormal LPA signaling. Moreover, schizophrenia, autism, and other developmental brain disorders have also been linked to fetal bleeding events and infections as well as ventricular abnormalities.
"It's something that we need to investigate further," said Chun, "but it may be that excess LPA exposure in an unborn child's brain can have a variety of adverse effects on development, depending on the part of the brain that's exposed, the stage of brain development, and the duration of the exposure."
Scientists at The Scripps Research Institute have found what may be a major cause of congenital hydrocephalus, one of the most common neurological disorders of childhood that produces mental debilitation and sometimes death in premature and newborn children.
The research appears in the September 7, 2011, issue of the journal Science Translational Medicine.
Hydrocephalus, which involves excess buildup of cerebrospinal fluid in the brain, affects about 1 in 500 children in the United States. Currently only symptomatic treatment exists—the surgical placement of a shunt to drain away excess fluid. Researchers want to know the condition's causes, so they can figure out how to prevent and treat it. Scientists have known for some time that hydrocephalus was linked to bleeding events in the developing brain, but the reason for that linkage has not been clear.
The new study now suggests that hydrocephalus can be triggered by abnormal levels of lysophosphatidic acid (LPA), a blood-borne lipid that can enter the brain in high concentrations during bleeding events, with profound effects on developing brain cells. The study showed that both blood and LPA itself acted through the same receptor (receptors are proteins to which one or more specific kinds of signaling molecules bind) to produce defects in the brains of developing mice that led to severe hydrocephalus; genetic removal of a specific LPA receptor or pre-treatment with a compound that blocked the receptor largely prevented the condition.
"This provides proof of concept for the medical treatment of this disease," said Jerold Chun, MD, PhD, a professor at Scripps Research and its Dorris Neuroscience Center, and senior author of the new study, "and it also hints that this mechanism involving LPA could be relevant to other neurological conditions associated with altered brain development."
>
Looking Ahead
LPA1-blocking drugs currently are being developed for other conditions including lung fibrosis, and the new finding from Chun's lab may lead biotech or pharmaceutical companies to study their use in hydrocephalus. "If you had an unborn baby who was at risk from an injury to the mother, an infection, or evidence of bleeding then, in principle, you could treat with a short-acting LPA1 blocker to prevent or reduce hydrocephalus," said Chun.
The discovery that excess LPA can wreak havoc in the developing brain could have broader implications as well. Abnormally high concentrations of LPA may be generated by fetal brain cells themselves, also producing abnormal LPA signaling. Moreover, schizophrenia, autism, and other developmental brain disorders have also been linked to fetal bleeding events and infections as well as ventricular abnormalities.
"It's something that we need to investigate further," said Chun, "but it may be that excess LPA exposure in an unborn child's brain can have a variety of adverse effects on development, depending on the part of the brain that's exposed, the stage of brain development, and the duration of the exposure."