Learning to walk, speak, and eat independently are milestones for every child. If, a few years later, these abilities are lost again and are accompanied by visual impairment, epilepsy, memory loss, and other cognitive impairments, the child is most likely affected by Batten disease. Researchers from the University of Graz, Graz University of Technology, and the Medical University of Graz have now discovered the cause of one form of this rare hereditary disorder. The findings were recently published in the journal Nature Cell Biology.
At the heart of the study is a lipid molecule known as BMP. It is found primarily in lysosomes, the cell’s “stomachs.” “They break down parts of the cell that are no longer needed. The resulting material is then exported and recycled. Among other functions, BMP plays an important role in the breakdown and processing of fat-like substances, explains Robert Zimmermann from the University of Graz. He summarizes the study’s findings as follows: “Mutations in the CLN8 gene can result in the body's inability to produce BMP. This leads to a lysosomal storage disorder known as Batten disease or neuronal ceroid lipofuscinosis. Until now, it was not known how closely the CLN8 gene defect is linked to impaired BMP synthesis in cells.”
Without BMP, increasing amounts of cellular waste accumulate in the body. The disease progresses slowly, which is why it is generally not apparent at birth but usually becomes noticeable and is diagnosed from early childhood onward. Nerve cells in the brain are particularly sensitive, which is why neurological symptoms are often among the first to appear. There is currently no cure for Batten disease. However, the findings open up avenues for new therapeutic approaches. “It would be interesting to investigate whether BMP supplementation could compensate for the deficiency caused by the genetic defect,” says Zimmermann, describing one possible approach that would need to be tested in further research.
Researchers from Cambridge Support the Findings
The publication was produced as part of the Special Research Area “Lipid Hydrolysis”, funded by the Austrian Science Fund FWF, and BioTechMed-Graz, the research alliance of the University of Graz, the Medical University of Graz, and Graz University of Technology. In addition to the research group led by Robert Zimmermann and first author Johannes Breithofer, both from the University of Graz, the teams led by Rolf Breinbauer at Graz University of Technology and Dagmar Kratky at the Medical University of Graz were involved. The researchers also worked closely with scientists at the University of Cambridge. Their colleagues in England, led by Kasparas Petkevicius, confirmed the findings in an independent publication.
Publication:
Breithofer J, Fawzy N, Zitta C, Tischitz M, Bulfon D, Hofmann C, Hartig L, Wagner C, Grabner GF, Pirchheim A, Lass A, Taschler U, Turner K, Petkevicius K, Stelzl U, Kratky D, Breinbauer R, Zimmermann R. Batten disease protein CLN8 enables a non-canonical phospholipid synthesis pathway. Nat Cell Biol. 2026 Sep 15. doi: 10.1038/s41556-026-02059-8. Epub ahead of print. PMID: 42744859.
