|
Even though sickle cell disease is a single-gene disorder, its symptoms are highly variable, with some patients experiencing frequent, severe pain crises and organ damage, while others are scarcely aware of their disease. In a recent study, scientists at Children's Hospital Boston, the Dana-Farber Cancer Institute and the Broad Institute reported five gene variants that could be helpful in predicting sickle cell disease severity, and perhaps lead to better treatments.
The gene variants influence blood levels of fetal hemoglobin (HbF), which affect symptom severity in sickle cell disease. "Understanding the factors giving rise to heterogeneity in HbF levels might allow us to take severely affected patients and make them more like those with more benign symptoms," says Children's researcher Vijay Sankaran.
A recent Children's study identifies a factor, called Otx2, that helps a key type of cell in the brain's cortex mature, initiating a period of heightened "plasticity" when the brain can readily rewire itself and, thus, learn. The work was done in the visual system, using a mouse model, but researcher Takao Hensch, PhD, speculates that similar factors may help time critical periods elsewhere in the brain. Timing is everything, because if the sensory system isn't fully developed, the brain won't set up its circuits properly. Being able to control the timing of critical periods could allow lifelong learning—as well as possibly ameliorating developmental disorders like autism and helping patients recover from stroke or brain injury.
 |
Up to 35 percent of babies surviving prematurity are left with neurologic impairment. Now, research from the Children's lab of Frances Jensen, MD, suggests that memantine (Namenda), used to treat Alzheimer's disease, may help break the cycle of brain damage. Memantine blocks N-methyl D-aspartate (NMDA) receptors, which premature newborns have in abundance, making them especially vulnerable to brain injury. If the drug proves to be safe, Jensen hopes to conduct a clinical trial in preemies.
 |
A recent Children's animal study finds promise in using neural stem cells to help repair spina bifida before birth. In spina bifida, a congenital defect that emerges around the fourth week of gestation, a portion of the spinal cord and its surrounding structures develop outside the body, causing partial paralysis, urinary and fecal incontinence and musculoskeletal deformities. Existing fetal surgery to repair it has led to only limited improvement. "To date, all that has been attempted is the prevention of further insult to the cord, rather than repairing damage that has already occurred," says researcher Dario Fauza, MD.
His team did typical in utero surgical repair, but also infused neural stem cells directly into the spinal cord. These cells then engrafted in the most damaged areas and produced factors that protect nerve cells and encourage nerve growth—the first steps in initiating a repair process. "Further studies will look at different forms of neural stem cells and alternative delivery methods," says study co-author Russell Jennings, MD.
|
