• What Is CRIA Syndrome?

News & Views

What Is CRIA Syndrome?

Mar 04 2020

After 20 years of unsuccessful diagnosis, new research from the National Human Genome Research Institute (NHGRI) has revealed the mechanics behind a mysterious auto-inflammatory disease. Known as CRIA syndrome, the disease is caused by mutations in the RIPK1 gene and triggers debilitating symptoms such as severe abdominal pain, fever, swollen lymph nodes, headaches, gastrointestinal problems and enlarged liver and spleen. The findings were published in the journal Nature, with NHGRI scientific director Daniel Kastner, M.D., Ph.D. saying that while CRIA syndrome isn't fatal it can have a tremendously negative impact on quality of life.

Exploring cause and effect

To investigate the causes of the condition, Kastner and his team analysed the genomes of each patient. After sequencing specific gene regions, they found that one gene in particular - RIPK1 - was mutated in all patients. Known as "missense" mutations, the variation changed a single DNA letter which subsequently altered the amino acid levels distributed to the encoded protein.

"It was as if lightning had struck three times in the same place," says Kastner. "This discovery underscores the tremendous power of combining astute clinical observation, state-of-the-art DNA sequencing, and the sharing of sequence data in large publicly-accessible databases. We live in a very special time."

Inflammation and cell death programming in overdrive

The RIPK1 gene creates codes for the RIPK1 protein, which plays an important role in managing inflammation and programming cell death. To regulate this function, a different protein "cuts" RIPK1 at a certain point in the sequence. For all patients suffering from the mysterious symptoms, the team observed DNA mutations in the location where RIPK1 is usually cut off. This allowed the RIPK1 protein to operate in overdrive and accelerate inflammation and cell death.

After identifying the cause-effect relationship between RIPK1 mutations and the associated symptoms, Kastner and his team named the disease cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. Working with researchers from the Walter and Eliza Hall Institute in Australia, the team create specialised mouse models to investigate the molecular mechanisms of CRIA syndrome and potentially develop a treatment strategy or cure. When trialled on patients, an immune system suppressing drug called tocilizumab significantly reduced the severity of CRIA syndrome symptoms. Moving forward, the researchers hope to explore how tocilizumab targets CRIA syndrome and whether the drug could be used to treat other auto-inflammatory conditions.

From developing new drugs to launching digital health strategies, innovation is at the heart of the life sciences sphere. Honouring a series of life sciences pioneers, 'OBN Awards Highlight Excellence in Life Sciences' recognises biotech start-ups, next generation immunotherapy companies, artificial intelligence forerunners and other industry leaders.


Digital Edition

LMUK 49.7 Nov 2024

November 2024

News - Research & Events News   - News & Views Articles - They’re burning the labs... Spotlight Features - Incubators, Freezers & Cooling Equipment - Pumps, Valves & Liquid Hand...

View all digital editions

Events

MEDICA 2024

Nov 11 2024 Dusseldorf, Germany

FILTECH

Nov 12 2024 Cologne, Germany

Intech

Nov 12 2024 Tel Aviv, Israel

analytica China

Nov 18 2024 Shanghai, China

Pharma Asia

Nov 20 2024 Karachi, Pakistan

View all events