A team of German scientists who received a $45,000 research grant from the NBIA Disorders Association in 2020 have successfully completed a stem cell model of FAHN to allow researchers to better understand the disease and test potential therapies for the disease.
FAHN (Fatty Acid Hydroxylase-associated Neurodegeneration) is a rare form of NBIA. The type of stem cell produced by the researchers is an induced pluripotent stem cell that can be programmed to develop into any type of human cell. The team developed the stem cells from skin fibroblasts of FAHN-Patients. This tissue contained copies of the mutated FA2H gene that causes the disease. The special ability of a stem cell to transform into any type of cell in the body now allows researchers to generate cells of the central nervous system that can be used by FAHN are affected.
The team was led by Dr. Andreas Hermann, together with Dr. Moritz Frech, Dr. Jan Lukas and PhD student Fatima Efendic from Rostock University Hospital. They collaborated with Dr. Sunita Venkateswaran from the University of Ottawa. She provided the skin fibroblast cell lines for research.
Researchers working at the FAHNresearch at the University Hospital Rostock,
from left to right: Dr. Jan Lukas, Dr. Moritz Frech, Fatima Efendic and Dr. Andreas Hermann.
The research project was entitled "In vitro disease modelling of fatty acid hydroxylase-associated neurodegeneration (FAHN): Patient-specific induced pluripotent stem cells and their neuronal derivatives as human models for FAHN".
Due to the COVID-19 pandemic, there were delays in the completion of the work, which is still ongoing. Third-party funding from the Center for Transdisciplinary Neurosciences Rostock at the University Medical Center Rostock will enable the project to continue until April 2023.
The researchers plan to produce further induced pluripotent stem cell lines, each of which carries different disease-relevant mutations. One focus is the development of protocols for the differentiation of these cells into oligodendrocytes.
In the central nervous system, oligodendrocytes form the myelin sheath that surrounds the axons of nerve cells and thus ensures rapid signal transmission. Since in the case of FAHNdegeneration of the myelin sheath occurs in patients, the team wants 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 function that occur as the disease progresses, researchers can test potential therapies to see if they can understand the effects of FAHN can turn around.
A published article about the work, "Generation of the human iPSC line AKOSi010-A from fibroblasts of a FAHNpatient carrying the heterozygous mutation p.Gly45Arg/p.His319Arg" is available for download online: https://www.sciencedirect.com/science/article/pii/S1873506122002124
The latest results of the project will be presented at the 8th International Symposium on NBIA, which will take place from 13 to 15 October 2022 in Lausanne, Switzerland.
(Published and translated with permission of the NBIA Disorders Association. The original English appeared in the NBIA Disorders Association newsletter, September 2022, translated with the free version of https://www.deepl.com/translator)