Blood-brain barrier children

There is no way of treating Tay-Sachs disease. Enzyme replacement is not considered a likely therapy because infused enzyme cannot penetrate the blood-brain barrier. However, the incidence of the disease has been dramatically decreased by prenatal diagnosis. Tay-Sachs disease is an autosomal recessive disease and so can arise only if both parents are carriers, i.e., if each parent carries a single defective gene for the hexosaminidase A enzyme. In that case there is a 25% chance that a child of these parents will have the disease. 

A drug is more likely to cross into the central nervous system (CNS) of a neonate rather than an older child or an adult. This most likely occurs because its CNS is less mature and the blood-brain barrier is less formed. This is an important consideration when antimicrobial therapy is needed for the treatment of bacterial meningitis or anticonvulsant for seizures. 

In young children (<3 years) the blood-brain barrier (an anatomical barrier that limits access to the brain) is not fully developed. Inorganic lead circulating in the blood is much more likely to reach the brain in an infant or a very young child. 

Lead, like merciuy, causes neimological diseases. The organolead compoimds are more toxic than mineral lead salts, since they are non-polar, lipid-soluble, and more readily cross the blood-brain barrier. This disease is related to child mental retardation, lower performance on I.Q. tests, and hyperactivity. Severe exposure in adults causes irritability, sleeplessness, and irrational behavior. Some have gone as far as to blame anti-social behavior and criminality on sub-clinical Pb poisoning. A correlation between Pb in blood and Pb in air, dust and soils has been observed in many studies. The U.S. Center for Disease Control has proclaimed a goal ofreducing blood lead contents in children below lO/ug/lOOmL. 

Evaluate eaoh of the three molecules, and determine if each molecule contains any funotional groups that will allow the drug to oross the blood-brain barrier and have an effeot on this child s alertness (create a list of relevant functional groups for each molecule). Based on your evaluation, whioh agent is likely to have the most significant effect Identify what property is necessary for these agents to cross this biological membrane. 

AdinolfiM. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 27 532-537. 

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