FYI, structural conformation diseases are actually quite common in humans, we just call them something different: amyloidoses. For example, TTR amyloidosis kills a good fraction of our oldest humans.
“Prions were originally defined as a unique class of infectious agents, whose infectivity relates solely to protein. In mammals, they cause fatal neurodegenerative diseases, such as Creutzfeldt-Jacob disease of man, sheep scrapie and bovine spongiform encephalopathy (reviewed in refs. 1 and 2). All these diseases are related to the PrP protein, whose conformationally altered form (PrPSc) is able to convert the normal host-encoded protein (PrPC) into this altered prion form. While only one prion protein is known in mammals, the prions appear to represent just a part of a much wider phenomenon, amyloidoses.
Amyloid diseases represent a group of more than 30 human diseases, which are characterized by deposition in different tissues of fibrous aggregates of conformationally altered proteins.”
The thing that makes prion diseases scary is that they’re potentially transmissible; but the reality is that even if you never catch a prion disease, a protein aggregation disease will eventually kill you if you live long enough.
There is a lot of drug development based on that theory and most of it came up empty and the one that didn’t came up empty was Abuhelm which is widely seen as one of the worst FDA drug approvals of recent years.
There are actually three amyloid antibodies that have shown some success: aducanumab (Aduhelm), lecanemab (Leqembi), and donanemab. I think the FDA approval of aducanumab was absolutely the right decision, though it’s far from a miracle drug.
I spent about six months of my life buried in the Alzheimer literature. There’s a mountain of evidence for this hypothesis. Take a look at my previous comments if you’re curious.
FYI, structural conformation diseases are actually quite common in humans, we just call them something different: amyloidoses. For example, TTR amyloidosis kills a good fraction of our oldest humans.
From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634591:
“Prions were originally defined as a unique class of infectious agents, whose infectivity relates solely to protein. In mammals, they cause fatal neurodegenerative diseases, such as Creutzfeldt-Jacob disease of man, sheep scrapie and bovine spongiform encephalopathy (reviewed in refs. 1 and 2). All these diseases are related to the PrP protein, whose conformationally altered form (PrPSc) is able to convert the normal host-encoded protein (PrPC) into this altered prion form. While only one prion protein is known in mammals, the prions appear to represent just a part of a much wider phenomenon, amyloidoses.
Amyloid diseases represent a group of more than 30 human diseases, which are characterized by deposition in different tissues of fibrous aggregates of conformationally altered proteins.”
The thing that makes prion diseases scary is that they’re potentially transmissible; but the reality is that even if you never catch a prion disease, a protein aggregation disease will eventually kill you if you live long enough.
There’s a formatting issue with the link, should be: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634591/
In particular, Alzheimer’s disease is a dual prion disease (amyloid-β and tau), and there are numerous other known prion diseases.
See Nguyen et al (2021). Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis and Shi et al (2021). Structure-based classification of tauopathies for some great detail on this.
There is a lot of drug development based on that theory and most of it came up empty and the one that didn’t came up empty was Abuhelm which is widely seen as one of the worst FDA drug approvals of recent years.
There are actually three amyloid antibodies that have shown some success: aducanumab (Aduhelm), lecanemab (Leqembi), and donanemab. I think the FDA approval of aducanumab was absolutely the right decision, though it’s far from a miracle drug.
I spent about six months of my life buried in the Alzheimer literature. There’s a mountain of evidence for this hypothesis. Take a look at my previous comments if you’re curious.