Cellular Model of a Rare Genetic Condition Created

Chronic granulomatous disease (CGD) is a rare hereditary condition that affects one in every 217,000 people worldwide and typically strikes patients at an early age, said scientists.

The first cellular model of chronic granulomatous disease (CGD) the rare genetic condition has been created by Sainte-Justine and Université de Montréal researchers. The study's findings were published today in the Journal of Allergy and Clinical Immunology.

"It is a primary innate immune defect that typically leads to severe, recurrent infections caused by bacteria and fungi, as well as potentially disabling lung inflammation or inflammatory colitis similar to Crohn's disease," said senior author Dr. Fabien Touzot, a clinical assistant professor in pediatric medicine at UdeM and researcher in pediatric immunology and hematology at CHU Sainte-Justine.

Chronic Granulomatous Disease-Causes-Symptoms-Diagnosis-Treatment-Complications
Chronic granulomatous disease is an inherited disorder in which immune system cells called phagocytes malfunction. It is also characterised by WBCs that cannot produce activated O2 compounds.

‘Chronic granulomatous disease (CGD) is a rare hereditary condition that affects one in every 217,000 people worldwide and typically strikes patients at an early age.’

"Currently, patients are forced to take antibiotics and anti-inflammatory drugs for the rest of their lives."

Gene editing shows the way forward

To better understand the mechanisms that trigger inflammation in patients with CGD, Touzot and his research team created the very first cellular model of the disease in their labs at CHU Sainte-Justine. They then used a technique known as gene editing to recreate and introduce into their model a genetic mutation that causes the disease. This allowed them to model the inflammatory response observed in patients and to study its mechanisms.

Basics of Rare Diseases - Types, Diagnosis and Treatment
Rare or orphan diseases are least understood of all chronic diseases. They are more common than projected and kill more people than cancer and HIV together.

"CGD is a hereditary illness caused by mutations in the NADPH oxidase enzyme. These mutations prevent white blood cells from working properly and, as a result, the patient's body can no longer defend itself against certain kinds of bacteria and fungi," said researcher Aissa Benyoucef, the study's first author.

"More than 90% of affected patients have inflammation that appears to be unrelated to infectious agents," he added. "Treating this inflammation is difficult, since it can put patients at increased risk of infection, which can sometimes be fatal. A better understanding of the mechanisms underlying the disease could help us develop new and more effective treatment strategies."

Patients are Prone to Infection in Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) patients are prone to recurrent and potentially life threatening bouts of infection due to the inability of phagocytic cells to kill invading microorganisms.

The research team showed that restoring NADPH oxydase function in defective cells would put the immune process back on track, thereby proving that this genetic mutation plays a direct role in causing inflammation.

"CHU Sainte-Justine is one of Quebec's leading centres of expertise in rare genetic diseases," said Touzot. "We're proud to serve patients by expanding the knowledge base in this area and by contributing to the development of precision medicine."

Test Your Knowledge on Rare Diseases
Rare or orphan diseases are the least understood of all the categories of chronic diseases. Rare diseases are more common than projected and globally they take away more lives than cancer and HIV combined.

Globally around 350 million people are estimated to live with a rare disease. Currently, there are 7000 rare diseases with newer ones being discovered each year. 80% of rare diseases have a genetic origin. Rare diseases may be single-gene disorders or multiple- gene disorders. Almost 50% of those affected are children and 30% of these children will not live beyond the age of 5. It takes nearly 7 years to diagnose a rare disease. 95% of rare diseases do not have a cure.

The new cellular model will be useful for the development of targeted treatments that are less toxic and more effective in treating inflammation, significantly improving patient quality of life, according to the researchers.

Source-Eurekalert