Dr. Young Seo, an assistant professor of nutritional biochemistry at the University of Michigan’s School of Public Health in Ann Arbor, gives an update on her work which will be completed in August 2021.
October 2020Ongoing BPAN research, funded by the NBIA Disorders Association, is producing new insights into iron accumulation and cell damage in individuals who have Beta-propeller protein-associated neurodegeneration.
BPAN is one of the most common NBIA disorders, which share a common characteristic of iron accumulation in the brain. Researchers are trying to understand what causes the iron to collect in BPAN and its impact on disease symptoms.
In September 2018, the NBIA Disorders Association awarded its first-ever early career grant for $150,000 to Dr. Young-Ah Seo, an assistant professor of nutritional biochemistry at the University of Michigan’s School of Public Health in Ann Arbor. The two-year grant was to end in August 2020 but will be extended 12 months because of a research pause during the COVID-19 pandemic.
Seo is investigating how a mutation in the WDR45 gene in BPAN individuals leads to iron accumulation and cellular damage. Her team was able to successfully generate a cell model of BPAN in which the WDR45 gene is deleted. This model showed significantly elevated iron levels, which suggests that the model mimics the condition seen in patients with BPAN.
Using this cell line, the team saw that the loss of WDR45 caused significant changes in the cellular pathways that regulate iron, which may underlie the reason iron accumulates in the brain of BPAN individuals. The team also found that the loss of WDR45 produces toxic reactive oxygen species, which are unstable molecules that can easily react and cause cell damage. This could contribute to the neurodegeneration seen in BPAN patients.
Taken together, the findings to date suggest that alterations in specific iron pathways increase total iron levels, promoting oxidative stress and cell damage in the BPAN cell model. Seo’s team is searching for molecular targets that can reduce iron levels in the cell model. Once the project is complete, it could point to potential therapies for BPAN.