Normal scar tissue forms to heal an internal wound and quietly retreats when the job is done. But in many common diseases — kidney, liver and lung fibrosis — the scar tissue goes rogue and strangles vital organs. These diseases are largely untreatable and ultimately fatal.
A new Northwestern Medicine study has newly identified a trigger of some fibrotic diseases and an experimental compound to treat it.
Fibrosis — a progressive scarring and hardening of internal organs — is estimated to cause 35 to 40 percent of deaths in the world. Fibrotic diseases include diabetic kidney fibrosis, alcoholic liver cirrhosis, hepatitis C, pulmonary fibrosis and nonalcoholic fatty liver disease, which may lead to fibrosis of the liver, the leading cause of liver transplant.
In one subset of human fibrosis cells, scientists discovered a delinquent gang of molecules that continually shouted at an immune receptor — the antennae on the cell — to produce scar tissue instead of quieting down and allowing the scar tissue to go back to sleep.
Scientists collaborated with a University of Colorado researcher who used crystallography and computer modeling to predict a molecule that could block the receptor that leads to the uncontrolled scarring. When they tested the molecule, T53, in three different mouse models of fibrosis, the abnormality was significantly reversed.
“Our study opens a new door into fibrosis by looking at it as an aberrant innate immune response and suggesting a novel approach to treat it,” said senior author Dr. John Varga, director of the Northwestern Scleroderma Program and the John and Nancy Hughes Distinguished Professor of Rheumatology at Northwestern University Feinberg School of Medicine.
The paper was published July 12 in the Journal of Clinical Investigation Insight.
“The leading cause of liver failure in western world is obesity and that’s because of liver fibrosis,” Varga said. “In the U.S., many of these diseases are lifestyle or age dependent. As we get fatter or older, they get worse.”
Most fibrotic disease likely begins as normal repair of an injury, scientists said. “But if the immune system produces too much of an initial scar, it can’t go back to normal,” Varga said. “You have an unhealed scar that keeps growing and can wipe out the entire organ.”
Not everyone’s fibrosis is caused by the same abnormality, Varga said. If the compound, T53, is eventually developed into an approved drug, it would be targeted to patients with the specific genetic signature identified in the study.
“There is an emerging direction for treating fibrosis with precision medicine,” said first author Swati Bhattacharyya, research associate professor of medicine in rheumatology and scientific director of the Scleroderma Research Laboratory at Feinberg. “Some people live with fibrotic disease for 30 years while others die in two years. We need to identify the rapid progressors from the slow progressors. That’s where precision medicine becomes really critical.”
“The results of this study are encouraging,” Varga said. “We are not saying this compound is ready to be a drug. It’s an initial compound that would need to be developed and tweaked. It would need significant funding to go to the next step.”
Learn more: Why internal scars won’t stop growing
The Latest on: Fibrosis
via Google News
The Latest on: Fibrosis
- Cystic fibrosis survivor wins Gordon Chesterman scholarship on February 19, 2019 at 2:00 pm
A cystic fibrosis survivor with a passion for Information Technology is the Wintec Gordon Chesterman scholarship recipient for 2018. Damien Bell, a second year Wintec student studying a Bachelor of In... […]
- Ocaliva shows fibrosis improvement in NASH on February 19, 2019 at 1:02 pm
Intercept Pharmaceuticals announced that Ocaliva met its phase 3 study primary endpoint of fibrosis improvement by 1 stage or more with no worsening of nonalcoholic steatohepatitis, according to a pre... […]
- Reading Hospital, Drexel College of Medicine launch Cystic Fibrosis clinic on February 19, 2019 at 11:56 am
Reading Hospital Tower Health and Drexel University College of Medicine announced recently they will collaborate on a cystic fibrosis clinic to be based in West Reading. Dr. Cecilia Smith, chairwoman ... […]
- 'Hunting Ground' Directors to Make Film Based on Memoir of Cystic Fibrosis Victim (Exclusive) on February 19, 2019 at 9:50 am
This week, Kirby Dick and Amy Ziering will begin filming the untitled documentary that chronicles the life of Mallory Smith, who died in November 2017, two months after receiving a double-lung transpl... […]
- Cystic Fibrosis scandal: UK waits for wonder drug to save children's lives on February 19, 2019 at 9:37 am
Starting at 6.30am, Charlotte Taylor, three, has a relentless routine of pills, therapies, physiotherapy and diet-specific meals - and she is deemed one of the UK's healthier CF youngsters. Currently, ... […]
- Ivy's fight for Orkambi drug to treat Cystic Fibrosis on February 19, 2019 at 7:51 am
A mother and daughter from Portsmouth are asking people to take part in a challenge to raise awareness of Cystic Fibrosis. Five-year-old Ivy Weir has the condition and her mother Gemma has started a p... […]
- Study links IGF-I to liver fibrosis risk in diabetes on February 19, 2019 at 7:33 am
Adults with type 2 diabetes who consumed very little alcohol daily may be at an increased risk for liver fibrosis if they have low levels of serum insulin-like growth factor I, according to findings p... […]
- How Intercept Pharma Shatters Expectations With Its Liver Fibrosis Treatment on February 19, 2019 at 6:50 am
In the primary efficacy analysis, the OCA 25 mg dosage met the primary endpoint of fibrosis improvement with no worsening of NASH at the planned 18-month interim analysis. Also, a numerically greater ... […]
- Directors of cystic fibrosis drug firm in NHS standoff made £15m on February 19, 2019 at 4:54 am
Vertex’s headquarters in Boston, Massachusetts. Photograph: Brian Snyder/Reuters Two UK directors of Vertex Pharmaceuticals, the company in a standoff with the NHS over the high price of its breakthro... […]
via Bing News