A possible solution found for TTR-related amyloid diseases

Conditions such as familial amyloid cardiomyopathy, which causes heart failure, and the neurodegenerative disease senile systemic amyloidosis are the result of a protein called transthyretin (TTR), which can form toxic clumps called amyloids. Researchers at Scripps and Stanford believe they've found some compounds that can prevent TTR from forming these clumps, eventually helping the hundreds of thousands of people who suffer from TTR-related amyloid diseases. Not only that, but the researchers say these new compounds might work even better than other TTR-stabilizing drugs currently in clinical trials.

"These new compounds have structures that make them very effective at stabilizing TTR in its stable native tetrameric form in laboratory tests, and they also seem nontoxic in cell culture," Stephen Connelly, a senior research associate in the Scripps Research laboratory of Professor Ian Wilson, says in a release. Connelly is lead author of a study appearing in Science Translational Medicine.

First, more about TTR. It does not work alone. They usually come in pairs of pairs called TTR tetramers and they transport the hormone thyroxine. However, in the busy bloodstream superhighway, the TTR tetramers can come apart and then stick back together in abnormal ways, forming amyloids. "It's well known that the body's normal defenses against amyloids decline with aging," Isabella Graef, a postdoc at the time of the research, said in a release. That's why TTR amyloids are found in the heart and other organs of 10% to 15% of people over 65 and never accumulate in young people.

Drugs currently being tested in clinical trials are non-steroidal anti-inflammatory drugs (NSAIDs), which come with the baggage of potentially harmful side-effects. So, Connelly and Graef have identified 33 potential TTR stabilizers that, importantly, do not harm normal cells. Now, they are in the process of narrowing them down to see which is most effective. "Together with physicians from a cardiovascular clinic here at Stanford, we're investigating whether these compounds can stabilize, in a solution of blood serum, the TTR proteins of patients with a common familial amyloid cardiomyopathy mutation," Graef said in the release. "If it can, then hopefully the pharmaceutical industry will want to develop it from there."

- read the ScrippsResearch Institute release
- and the abstract in Science Translational Medicine

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