Tech

This Gulp of Engineered Bacteria Is Meant to Treat Disease


In the mud In the trenches of World War I, thousands of soldiers on both sides fell ill with dysentery, a diarrheal disease often spread by contaminated water. Curiously, a German soldier deployed in the Balkans didn’t get sick when the rest of his comrades got sick. When scientist Alfred Nissle isolated a strain E coli from the soldier’s chair in 1917, he noticed that it had a strong protective effect against Shigella bacteria, a cause of dysentery.

For hundreds of years, this protective strain — now known as E. coli Nissle—Has been used as a probiotic to promote gut health and to treat gastrointestinal conditions such as inflammatory bowel disease. Now, scientists are studying genetic engineering E. coli Nissle to perform specific functions in the hope of creating a new “living” drug.

In October, the Massachusetts biotech company Synlogic publish the result from a small study shows that the engineered bacterial version offers some benefit to patients with a rare genetic disease called phenylketonuria, or PKU. People with this disorder are unable to break down an amino acid called phenylalanine – or Phe for short – found in protein-rich foods like meat and eggs. If left unchecked, phenylalanine can build up in the brain and cause intellectual disability, seizures, and behavioral symptoms.

In a phase 2 trial, the company showed that their engineered bacteria, which 20 volunteers drank mixed into a liquid, reduced levels of that amino acid. “Although the study has not yet been published in a peer-reviewed journal, the results point to a method,” said Timothy Lu, associate professor of electrical and biological engineering at MIT and co-founder of Synlogic. new way to treat diseases you can program a computer, we can modify the DNA of bacteria and ask them to do things like produce a drug at the right time and in the right place, or in the case of This breaks down a toxic metabolite. “

PKU is usually treated with a carefully restricted low-protein diet. Newborns who test positive will be given a special formula as soon as possible. Children and adults with the disease must avoid meat, fish, eggs, and dairy products, and many continue to take medical formulas or take supplements to make sure they’re getting enough nutrients. The severity of the disease varies, with some patients consuming only a few grams of protein per day. (A simple piece of white bread contains 1 or 2 grams of protein.) There are two drugs approved to treat PKU, but one is not widely used because it can cause severe allergic reactions and the other only helps people with certain diseases. type of PKU.

Aoife Brennan, president and chief executive officer of Synlogic, said the company wants to give patients more freedom to eat what they can. “They understand how important controlling the Phe is to their brain health. But what they really want is a little relief from this extremely strict diet,” she said.

To achieve that, the scientists at the company genetically engineered E. coli Nissle to make an enzyme found in plants, yeast, and other bacteria whose job it is to swallow phenylalanine. They also removed a gene from the bacteria so it wouldn’t replicate in the gut. This is to ensure that the bacteria will not reside permanently and potentially cause gastrointestinal problems later on. Brennan says the engineered bacteria will be cleared from the digestive tract in a week.

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