Researchers Discover a Therapeutic Target for Wiskott-Aldrich Syndrome


Scientists have known for years that Wiskott-Aldrich syndrome (WAS) is caused by a gene on the X chromosome. The gene (the WASP gene) can be found throughout the immune system and in cells in the blood called cytoskeletons. The WASP maintains the protein networks that determine the organization and shape of the cells.

Now researchers at KAUST in Saudi Arabia in collaboration with California’s Salk Institute recently discovered the cause of the WAS disorder which leads to immune deficiencies with severe platelet abnormalities. The findings yield molecular clues leading to potential treatments for WAS.

Life-Threatening Symptoms

WAS affects approximately one in 100,000 infants with symptoms such as frequent bleeding and infections. Inflammatory diseases as well as various cancers are also on the list of life-threatening complications.

A bone marrow transplant helps some children, but carries with it a host of complications and risks.

RNA Splicing Factors

Biologist Mo Li and KAUST researchers created a panel of pluripotent stem cells (iPSCs) taken from patients who had an immunological deficiency. Additionally, gene editing was used to repair mutational iPSCs or to delete the WAS gene. This resulted in paired stem cells that were identical in every way except for the WAS gene continuance.

The researchers discovered that WAS genetic mutations interfered with the RNA splicing process and prevented anti-inflammatory and immune proteins from forming correctly.

Cells that do not have a working version of WASP have high levels of RNA splicing factors. The elevated levels of splicing factors create shortened transcripts and disrupt protein function.

Co-author Baolei Yaun, Ph.D. student, explained that WASP has been shown to participate in RNA splicing. He pointed out that WASP deficiencies could be corrected through SRSF2, a serine and arginine-rich splicing factor 2. This was evident by the targeting of SRSF2, which helped to prevent molecules that caused inflammation to be released.

The researchers conducted additional experiments and found that repairing the WASP mutations remedied the RNA splicing issues. As aforesaid, lowering levels of SRSF2 prevents the release of inflammation-causing molecules.

The study results involving the way cells cut and paste RNA strands (RNA splicing), were published in the Journal Nature Communications on June 25, 2022, and can be found here.

In conclusion, targeting SRSF2 appears to have potential as a treatment approach for the Wiskoff-Aldrich syndrome.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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