S01E09 | Fatal Familial Insomnia A Comprehensive Review скачать в хорошем качестве

S01E09 | Fatal Familial Insomnia A Comprehensive Review

Fatal Familial Insomnia: A Comprehensive Review—Genetics, Pathophysiology, and the Human Cost DOI: 10.5281/zenodo.16971269 ABSTRACT This episode takes a deep dive into Fatal Familial Insomnia (FFI), an exceptionally rare prion disease that robs its victims of the ability to sleep—and ultimately of life itself. We explore its discovery, genetics, and molecular underpinnings, beginning with the PRNP D178N mutation and codon-129 polymorphism that dictate whether the outcome is FFI or familial Creutzfeldt-Jakob disease. The discussion unpacks how protein misfolding spreads chaos in the brain, why the thalamus is uniquely vulnerable, and how FFI reshapes our understanding of sleep, consciousness, and neurodegeneration. We walk through its devastating four-stage progression, highlight diagnostic puzzles, and examine the current landscape of symptomatic management, genetic counseling, and experimental therapies—from doxycycline prevention trials to cutting-edge ASO and CRISPR gene-editing approaches. Beyond science, we reflect on the profound human impact, the burden on families, and the existential anxiety of carrying a 50% genetic risk. This is both a sobering and inspiring journey into one of neurology’s most fascinating frontiers. CLINICS & SERVICES Book an appointment: https://appointments.conciercare.net/... Read more about FFI in the CONCIERCARE newsroom: https://health.conciercare.net/news/p... OBJECTIVES 1. What is Fatal Familial Insomnia (FFI), and what distinguishes it from other neurodegenerative diseases? 2. Explain the specific genetic mutation and polymorphism combination that causes FFI. 3. Describe the primary neuropathological signature of FFI in the brain. 4. What is agrypnia excitata, and how does it relate to the pathophysiology of FFI? 5. Why are conventional hypnotic medications ineffective in treating the insomnia associated with FFI? 6. List three distinct core clinical features of FFI beyond just insomnia. 7. What is the "pathological paradox" observed in FFI regarding PrPSc accumulation and neurodegeneration? 8. Briefly explain the role of functional neuroimaging (PET) in diagnosing FFI. 9. How does Sporadic Fatal Insomnia (sFI) differ from FFI, despite their similar clinical presentations? 10. What is the rationale behind the most promising future therapeutic strategies for FFI, such as gene-targeting therapies? Join the conversation—What do you think studying FFI can teach us about broader neurodegenerative disorders like Alzheimer’s or Parkinson’s? Share your perspective in the comments. ABOUT US CONCIERCARE is a neuroscience-centered health system committed to advancing rare disease research, precision therapies, and compassionate patient and family support. Learn more at: https://health.conciercare.net COPYRIGHT & DISCLAIMER https://health.conciercare.net/news/p... - Funding & Ethical Disclosures #FatalFamilialInsomnia, #PrionDisease, #Neurodegeneration, #SleepDisorders, #Thalamus, #CJD, #Genetics, #ProteinMisfolding, #CRISPR, #ASO, #RNAi, #Neuroscience, #RareDiseases, #PatientAdvocacy