Stunning finding: Compounds protect against cere...(play a role in cerebral palsy. After...),Health

After a lengthy drug development process, Silverman went to his collaborator Sidhartha Tan, M.D., a neonatologist from NorthShore University HealthSystem, to test the two best compounds on Tan's cerebral palsy animal model. A diminished supply of oxygen (hypoxia) from mother to fetus causes an increase in nitric oxide levels in the brain, which leads to brain damage and newborns with cerebral palsy characteristics.

Silverman and Tan wanted to see if they could prevent brain damage in the fetuses by administering one of the compounds to the mother before the hypoxic event. They expected some degree of success but were surprised by how effective the treatment was. The researchers attribute the protection from cerebral palsy to the decrease in the brain enzyme and the nitric oxide that is produced.

"We still have to bring the phenomenon to humans, which would be very exciting," said Tan, who has been investigating the impact of nitric oxide on neuronal damage. "There is such a dire need. If we could safely give the drug early to mothers in at-risk situations, we could prevent the fetal brain injury that results in cerebral palsy."

In developing the potential drugs, Silverman and his team were able to produce something that pharmaceutical companies so far have not: highly selective compounds that inhibit the enzyme found in brain cells that produces nitric oxide but that do not affect similar nitric oxide-producing enzymes found in endothelial and macrophage cells.

Endothelial cells regulate blood pressure, and macrophage cells play an important role in the immune system. Reducing their production of nitric oxide would have deleterious effects on an animal, such as increasing blood pressure or compromising the immune system.

"The challenge was to lower only the nitric oxide in the brain and not in the other cells where the nitric oxide is very important," said Silverman, a member of
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