ASAN, South Korea – A widely used gout medication may offer a new therapeutic approach for Gaucher disease, according to a recent laboratory study that identified colchicine as a promising candidate for drug repurposing.
Researchers found that colchicine, an oral anti-inflammatory drug approved for gout and certain cardiovascular conditions, significantly reduced fat accumulation and cellular stress in a cell-based model of Gaucher disease. The findings suggest the decades-old medication could potentially be adapted to treat the rare inherited disorder.
The study, published in Analytical Biochemistry under the title A bioinformatics-guided analytical approach for drug repositioning: Colchicine as a candidate for gaucher disease treatment, used computational biology techniques to uncover biological pathways shared between Gaucher disease and melanoma, an aggressive form of skin cancer.
Gaucher disease and its broader disease links
Gaucher disease is caused by mutations in the GBA1 gene, which provides instructions for producing the enzyme glucocerebrosidase, or GCase. This enzyme helps cells break down certain fatty substances inside structures called lysosomes. When GCase is deficient or malfunctioning, fatty molecules accumulate within cells, leading to inflammation, cellular dysfunction, and a wide range of symptoms affecting the liver, spleen, bones, and nervous system.
People with Gaucher disease also have a higher risk of developing malignant melanoma, the deadliest type of skin cancer. In addition, carrying a mutated GBA1 gene significantly increases the risk of Parkinson’s disease, which has also been associated with melanoma. Despite these known links, the biological mechanisms connecting the conditions remain poorly understood.
Using bioinformatics to identify new treatments
The research team at Hoseo University in South Korea explored whether drugs already approved for other conditions could target shared disease pathways in Gaucher disease and melanoma.
Drug repurposing — finding new therapeutic uses for existing medications — is considered an attractive strategy because it can dramatically reduce development time, cost, and safety risks compared with creating entirely new drugs.
Using bioinformatics tools to analyze large-scale gene activity datasets, the researchers examined tissue models of GBA-mutated Parkinson’s disease alongside melanoma samples. Their analysis identified 121 genes that were altered in both diseases.
Further computational screening narrowed the list to 14 highly connected “hub genes” that appeared central to disease-related biological networks. Among these, one gene known as CCN2 consistently showed elevated activity across multiple datasets involving melanoma and lysosomal disorders related to Gaucher disease.
The researchers then screened approved drugs known to interact with CCN2. Eight potential candidates emerged, including dexamethasone and losartan. However, colchicine demonstrated the most stable and consistent binding to the CCN2 protein, making it the leading candidate for further testing.
Colchicine reduced oxidative stress and fat buildup
Colchicine is a plant-derived alkaloid extracted from Colchicum autumnale, commonly known as the autumn crocus. The medication has been used for more than 2,000 years to treat gout and is recognized for its broad anti-inflammatory effects. It is also approved to reduce the risk of heart attack, stroke, and cardiovascular death in some patients.
To test the drug’s potential in Gaucher disease, researchers used a laboratory model in which cells were treated with CBE, a compound that blocks GCase activity and mimics key features of the disease.
Cells exposed to CBE showed increased levels of reactive oxygen species — unstable molecules that drive oxidative stress and cellular damage. When colchicine was added, oxidative stress levels declined significantly. The drug also reduced the abnormal buildup of fatty molecules caused by GCase inhibition.
“The results demonstrated that colchicine significantly suppressed lipid accumulation, suggesting its potential as a therapeutic candidate for Gaucher disease,” the researchers wrote.
More research still needed
Although the findings are encouraging, the scientists emphasized that the work remains in the preclinical stage. So far, colchicine has only been studied in laboratory-grown cells, and additional research will be required to determine whether the drug is safe and effective for people with Gaucher disease.
“In this study, we used bioinformatics to identify CCN2 as a key common biomarker linking Gaucher disease and melanoma,” the researchers concluded, adding that the work also “demonstrated the therapeutic potential of the candidate drug, colchicine.”
Contact
Jeongin Kim
College of Biohealth – Hoseo University