Green tea compounds show promise for treating the genetic disorder hyperinsulinism/hyperammonemia

Prevailing medical evidence suggests that the deadly genetic disorder hyperinsulinism/hyperammonemia is rare.

But Dr. Thomas Smith, a researcher at the Donald Danforth Plant Science Center, questions whether that's true.

He and researchers at the Children's Hospital of Philadelphia have found green tea compounds that show great promise for treating the disorder, which causes insulin to rocket to dangerously high levels and glucose to plummet when patients who have the disorder eat a little too much protein. They often go into a coma then die.

Perhaps, Smith said, a lot of children die before they're diagnosed, and the disorder is more common than believed.

"Unless doctors happen to know what they're looking for, it's hard for them to pick up on, unless they happen to be monitoring baby glucose levels," he said. Getting funding to develop the green tea compounds into a safe, effective drug is difficult because hyperinsulinism/hyperammonemia syndrome — or HHS — is considered an orphan disease.

So Smith has pinned his hopes on studies at Harvard University and University of Texas where researchers took findings from his study and the one at Children's Hospital of Philadelphia, expanded on them and found that the same green tea compounds appear to kill gioblastomas, an aggressive brain tumor, and tuberous sclerosis complex disorder, which causes non-malignant tumors to grow on multiple organs.

"If we can use the cancer as an excuse to test the (green tea) drug and develop it, it might provide a way back toward curing HHS," he said.

The root cause of HHS is glutamate dehydrogenase, a compound that is found in all living organisms and is responsible for digesting amino acids.

It's emitted from the liver, kidney, brain and pancreatic beta-cells and is regulated by a complex network of metabolites in animals. It occurs when the glutamate compound isn't properly regulated. When patients who have the disorder eat protein, their pancreas secretes too much insulin and they become severely hypoglycemic.

Smith and his colleagues used atomic structures to understand the differences between plants and animals. Then they found that two compounds in green tea, when taken orally, turn off glutamate dehydrogenase which compensates for the genetic disorder.

Smith's goal is to develop the compounds into a digestible drug, because giving babies green tea would not work.

"They need a pretty big dose. It would be the equivalent of 10 cups of tea given to mice, and green tea has a lot of caffeine so it's working against you," he said.

He recently wrote a grant to study ways to turn the green tea compounds into a safe, effective and digestible drug that researchers at Harvard and University of Texas can "throw against their tumors."

His chances of getting funding for a study related to cancer, he said, are better than for one related to a rare genetic disorder.

He compares his funding issues to when researchers at Duke University wanted to study drugs for the common cold.

The common cold is not fatal, so drugs for it have to be safe as water, he said. Meanwhile, diseases such as encephalitis, which are in the same family, are fatal, so there's more funding to prove the safety and efficacy of the same drug for those diseases.

Smith has been studying green tea's effects on the disorder for more than 30 years when he was an undergraduate. "I thought we'd have this licked by now," he said. "It's a natural, digestible compound, but you still have to go through jumps and hoops."

Plus, he added, green tea as a drug has gotten a black eye in recent years and scientists must go the extra 10 miles to prove it does what they say.

"There have been a lot of bad papers out there that weren't carefully done," he said. "Talk to enough chemists and some will say it cures bunions, baldness and everything. The problem is they're goofy studies using ridiculous concentrations to get the antioxidant effect."