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| Researchers working on FAHN research at the University Medical Center Rostock. L-R Dr. Jan Lukas, Dr. Moritz Frech, Fatima Efendic, and Dr. Andreas Hermann. |
A team of German scientists who won a $45,000 research grant from the NBIA Disorders Association in 2020 has successfully produced a stem cell model of FAHN, which researchers can use to better understand the disorder and test potential therapies for this disease.
FAHN, or Fatty Acid Hydroxylase-associated Neurodegeneration, is a rare form of NBIA. The type of stem cell the researchers produced is an induced
pluripotent stem cell, which can be programmed to develop into any type of human cell.
The team developed the stem cells from skin fibroblasts from FAHN patients. This tissue contained copies of the mutated FA2H gene that causes the disease. The special ability of a stem cell to turn into any type of cell in the
body now allows the researchers to generate central nervous system cells affected by FAHN.
The team was led by Dr. Andreas Hermann, along with Dr. Moritz Frech, Dr. Jan Lukas and PhD student Fatima Efendic, of the University Medical Center Rostock. They teamed up with Dr. Sunita Venkateswaran from the University of Ottawa. She provided the skin fibroblast cell lines for the research.
The research was titled “In vitro disease modeling of Fatty Acid Hydroxylase-associated Neurodegeneration (FAHN): Patient specific induced pluripotent stem cells and their neuronal derivatives as human models of FAHN.”
The COVID-19 pandemic caused delays in completing the work, which is ongoing. Third-party funding through the Center for Transdisciplinary Neuroscience Rostock at the University Medical Center in Rostock, Germany, will allow the project to continue through April 2023.
Researchers plan to create additional induced pluripotent stem cell lines, each carrying different disease-relevant mutations. One focus is establishing protocols for differentiation of these cells into oligodendrocytes. Oligodendrocytes generate the myelin sheath in the central nervous system, which surrounds the nerve cell axons and thus ensures rapid signal transmission. Because degeneration of the myelin sheath occurs in FAHN patients, the team aims to investigate the causes of these disorders of the myelin sheath using the newly established model system.
With a better understanding of the abnormal changes in cell functions that occur during disease progression, the researchers can advance to testing potential therapies to see whether they can reverse FAHN’s effects.
A published paper on the work, “Generation of the human iPSC line AKOSi010-A from fibroblasts of a female FAHN patient, carrying the compound heterozygous mutation p.Gly45Arg/p.His319Arg,” is available online. Latest results of the project will be presented at the 8th International Symposium on NBIA, taking place from October 13th to 15th, 2022, in Lausanne, Switzerland.
