Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
‘Unknown’ enzyme may be key to new treatment for inflammatory diseases

‘Unknown’ enzyme may be key to new treatment for inflammatory diseases

An enzyme that normally repairs damaged DNA, may be the key to a new treatment for inflammatory diseases.

Inflammatory diseases such as COPD and septicemia (blood poisoning) represent a growing threat to public health. Such conditions are commonly the result of an overactive immune system.

This is why the discovery of the drug candidate TH5487 arouse so much attention. The molecule disarms a protein that appears to play a key role in inflammatory diseases, and experiments have shown that it suppresses lung inflammation in mice.

The discovery has been made by research scientists at the Karolinska Institute in Stockholm, Stockholm University, the University of Texas, and at NTNU and SINTEF in Trondheim, Norway. After a five-year research project, the results were published in the journal Science.

Key signal substance causes overactivity

Patients suffering from inflammatory diseases possess large amounts of a signal substance, known to biochemists as ROS. ROS is an abbreviation for “reactive oxygen species”, which triggers inflammation and damages the genetic material, DNA, in our cells. “This damage is repaired by the enzyme OGG1.

Our research shows that this “repair” also acts as a trigger promoting overactivity in the immune systems of those patients suffering from auto-immune diseases, explains the Norwagian researcher Torkild Visnes at SINTEF.

“It may sound illogical, but in many diseases it is an overactive immune system that constitutes the problem” he says.

This finding agrees with previous research showing that mice lacking the OGG1 enzyme are unable to activate a powerful immune response. As a result, these mice experience milder inflammation than normal mice.

Painstaking study of 18,000 substances

“Our idea was to look for a chemical substance that would attach itself to the repair protein OGG1”, says Visnes. “This substance would then be used to “disarm” the protein by persuading it to respond as if it had already found damaged DNA, and in doing so inhibit its activity. In other words, deprive the protein of its ability to trigger an overactive immune response”, he explains.

“I had previously been working exhaustively to measure activity levels of this class of enzyme using very laborious approaches”, Visnes explains. “But by developing a method that made it possible to determine enzyme activity using fluorescence (repaired DNA can be made to fluoresce), we were able to measure thousands of samples in the space of just a few hours”, he says.

“After examining 18,000 possible substances for properties that might fool the repair enzyme, the research team finally identified a substance that succeeded in deactivating OGG1. The process had taken a year to complete”, says Visnes.

Further development in the lab

Then began the laborious process of refining the substance so that it possessed all the properties needed to function in a living cell.

Over a two-year period the research team made about a thousand variations on the basic substance and were finally left with the promising drug candidate TH5487, named simply as a result of being made after the variant TH5486.

TH5487 proved to have all of the three key properties that the researchers were looking for:

  1. It attached itself to the inflammation protein OGG1, inhibiting its activity and preventing it from bonding with DNA.
  2. It was able to deactivate OGG1 in living cells.
  3. It was very stable when injected into lab animals.

Healthier mice in Texas

The breakthrough came when researchers at the University of Texas tested the substance on mice suffering from serious cases of lung inflammation.

TH5487 rapidly and effectively prevented the lung cells from activating inflammation genes. As a result, immune cells were unable to register the developing infection and thus kept away from the lungs. Sensationally, the condition of the mice improved. The research team thus believe that they have discovered a new approach to suppressing inflammation that can be used instead of, or as a supplement to, existing treatments.

“The aim is to develop a drug that can work on people”, says Visnes. “This will be a long journey because it is expensive and the regulations are complex. But we believe that we’ve now discovered a piece in the puzzle that may have major significance for the treatment of everything from auto-immune diseases to blood poisoning”, he says. Visnes now wants to establish a separate biochemistry research group in Trondheim focusing on DNA and drug development.

Source:

https://geminiresearchnews.com/2018/11/experiments-shows-that-an-unknown-enzyme-fights-inflammation/

About author

Related Articles