Drug repurposing screen identifies dopamine pathway as candidate therapy for PIGA-CDG
Researchers publishing in PLOS Genetics have found that dopamine signalling may offer a therapeutic avenue for PIGA-CDG, a rare congenital disorder of glycosylation with few current treatment options.
Miriam C. Aziz, Jennie Wilson, and Clement Y. Chow at the University of Utah have published a drug repurposing screen in PLOS Genetics identifying dopamine signalling as a candidate therapeutic pathway for PIGA-CDG, a congenital disorder of glycosylation caused by pathogenic partial loss-of-function variants in the PIGA gene.
PIGA encodes an enzyme that catalyses the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis — the attachment of N-acetylglucosamine to phosphatidylinositol. Loss of this function has wide phenotypic consequences but primarily manifests as neurological symptoms including seizures, intellectual disability, and developmental delay. Existing management focuses on symptom control rather than the underlying mechanism.
Using a systematic screen of approved and investigational compounds, the team identified drugs acting on dopamine signalling as candidates capable of modifying the disease phenotype in their model system. The authors note that the findings are preliminary and that further work is needed to establish whether the pathway represents a viable therapeutic target in human PIGA-CDG.
The study is published in PLOS Genetics (DOI: 10.1371/journal.pgen.1012294). Because PIGA-CDG is a rare disorder with a defined genetic basis, the findings are likely to be of particular interest to researchers working on congenital disorders of glycosylation, as well as to genetic counsellors supporting affected families.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
PIGA-CDG is a rare inherited condition caused by a fault in a gene called PIGA. This gene makes a protein that helps attach certain molecules to the surface of cells. When it does not work properly, it mainly affects the nervous system, causing seizures, learning difficulties, and developmental delays. At present there are very few specific treatments, and care focuses on managing symptoms.
Researchers publishing in the journal PLOS Genetics have used a method called drug repurposing — testing existing medicines to see whether any might help — and found that drugs affecting a chemical messenger in the brain called dopamine could be worth investigating further. This is early-stage laboratory research, and the scientists say more work is needed before any conclusions can be drawn about treatment in people.
This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
Read the original reporting — these are the public sources this summary draws from.
-
Primary source PLOS Genetics · 2026-08-31A drug repurposing screen reveals dopamine signaling as a candidate therapeutic pathway for PIGA-CDG