Innovative Zebrafish Study Offers Hope for Rare Lymphatic Disease Treatment

Researchers from the Weizmann Institute of Science and Sheba Medical Center have made significant strides in understanding and potentially treating kaposiform lymphangiomatosis (KLA), a rare and severe genetic disorder affecting the lymphatic system. This condition causes abnormal enlargement and distortion of lymphatic vessels, leading to symptoms like fluid buildup in the chest, skin issues, and organ complications. The breakthrough came through the use of zebrafish embryos, which share key genetic and developmental features with humans.

The collaboration was prompted by a young patient at Sheba’s Safra Children's Hospital, who presented with breathing difficulties due to fluid accumulation. Greenberger’s team identified a mutation in the NRAS gene, which is linked to cell proliferation and cancer. Traditional treatment methods involving cancer drugs targeting NRAS often have severe side effects and limited efficacy. To find safer, more effective options, scientists created a zebrafish model that expressed the mutated human NRAS gene specifically in the lymphatic system.

This model showed lymphatic abnormalities mirroring human KLA, with enlarged vessels and swollen hearts, confirming the mutation’s causative role. Using high-throughput screening combined with AI-powered imaging, the team tested approximately 150 existing drugs. Two compounds stood out, successfully reversing the lymphatic and cardiovascular anomalies in the zebrafish model.

These promising drugs also demonstrated effectiveness on human lymphatic cells derived from the original patient, reducing abnormal sprouting associated with KLA. Notably, these drugs have better safety profiles than current cancer therapies, paving the way for clinical trials. The researchers aim to initiate multi-center trials to evaluate their potential in patients.

The study also advances understanding of why NRAS mutations selectively damage lymphatic vessels without affecting arteries or veins. Since the identified drugs are already approved for other uses, repurposing them for KLA could significantly accelerate treatment availability, offering new hope for patients with this challenging condition.

Source: https://medicalxpress.com/news/2025-09-fishing-drug-rare-disease.html