Boston, MA – New research conducted by scientists at Boston University reveals groundbreaking findings on prion disease mutations and their impact on neuron synapses long before symptoms appear. The study, which focused on neurons derived from induced pluripotent stem cells (iPSCs) of patients with the E200K prion protein mutation, uncovered significant alterations in neuron-to-neuron contact sites, even in the absence of misfolded prion proteins. This discovery suggests that prion diseases may involve a loss of normal prion function, leading to early brain damage.
Prion diseases, which typically present with cognitive difficulties, poor muscle control, and jerking movements, have three major phenotypes: genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. The E200K mutation of the prion protein (PrP) is a common cause of inherited prion diseases, believed to make PrP more susceptible to misfolding into a pathogenic shape (PrPSc).
Researchers at Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center conducted the study, led by Dr. David A. Harris. The team created iPSCs from a family carrying the E200K mutation, differentiating them into neurons for comparison between mutation carriers and non-carriers. Using CRISPR/Cas9 technology, they corrected the mutation in some lines to allow for comparisons between neurons with identical genetic backgrounds.
According to co-author Dr. Gustavo Mostoslavsky, iPSC-derived neurons offer valuable insights into the pathogenesis of genetic prion diseases and serve as a promising platform for testing potential therapeutics. The study, which represents a significant step towards personalized medicine, highlights the importance of understanding the early stages of neurodegenerative disorders like prion diseases.
The findings of this research not only provide a deeper understanding of prion diseases but may also offer insights applicable to other neurodegenerative conditions, including Alzheimer’s disease. The study suggests that abnormalities in neurons may be detectable long before the onset of symptoms, emphasizing the importance of early intervention in combating these devastating disorders. The study, published in Stem Cell Reports, sheds light on potential treatments that could be effective in addressing the symptoms of inherited neurodegenerative diseases.