The drug’s developer, Roche, along with Banner Alzheimer’s Institute, the Phoenix-based organization helping lead the study, announced the negative results Thursday. After years following a family believed to be genetically predisposed to the disease, researchers found no significant difference in cognition or the ability to store and retrieve new memories between participants who received the drug and those who got placebo.
Amyloid is bust. Pharma have moved on upstream to soluble oligomers vs targeting plaques, and even these are just “barely” slowing down progression, with some serious side effects (ARIA: Amyloid Related Imaging Abnormalities). We still do NOT know root cause. It’s very likely polygenetic, so finding a pharma narrow “single” pathway magic bullet is going to be prove extremely difficult.
Here’s a great paper on Rapamycin and ADDITIONAL therapeutic pathways! Amazing.
And they didn’t even measure pmTOR directly!
Rapamycin confers neuroprotection against aging-induced oxidative stress, mitochondrial dysfunction and neurodegeneration in old rats via activation of autophagy https://sci-hub.se/10.1089/rej.2018.2070
Animals were randomly allocated to the following four treatment groups having 12 rats in
each group.
Young control: Young rats were given single oral administration of vehicle solution (0.9%
NaCl solution containing 0.5% DMSO) for 4 weeks daily.
Young rapamycin: Young rats were given single oral administration of rapamycin (0.5
mg/kg b.w.) for 4 weeks daily.
Old control: Old aged rats were given single oral administration of vehicle solution (0.9%
NaCl solution containing 0.5% DMSO) for 4 weeks daily.
Old rapamycin: Old aged rats were given single oral administration of rapamycin (0.5
mg/kg b.w.) for 4 weeks daily.
The dose of rapamycin (0.5 mg/kg b.w.) was selected on the basis of our earlier published reports.
0.5mg/kg/bw in rats to humans is about 5.6mg @ 70kg human. A hefty daily dose.
Clearly though, getting enough Rapamycin into the brain is key…but how much and what dosing? This isn’t a walk in the park, few mg/week?? We just don’t know!
“Our data demonstrated the significant age-related oxidative stress, apoptotic cell death, elevated inflammatory response, and reduced level of markers associated with rejuvenation and neural integrity including the activities of ion channel transporters and acetyl cholinesterase (AChE) in the brain of old aged rats. Furthermore, rapamycin (0.5 mg/kg b.w. for 28 days) induced activation of autophagy provided significant protection to aging rat brain by reducing the aging-induced oxidative stress, apoptotic cell death, and markers of neurodegeneration.”
I don’t think I’ve seen a rapamycin paper showing so many impacted pathways. Inflammation reduction in old cohort was HUGE.
Very nice article. Many of those protective mechanisms would help in virtually all age related diseases, including cardiovascular.
Some studies are showing a link between brain inflammation involving the microglia and CAD . The body is very intertwined. Not an island as the gut microbiome is proving.
A big blow to the amyloid theory. Again.
Doesn’t mean that amyloid is totally irrelevant but it doesn’t appear to be the central actor.
It’s very complex. People treated with anti viral meds for herpes have much less risk.
Exercise and viagra help showing a vascular connection.
Mitochondria, autophagy, senescence, on and on it goes.
But is the rapamycin- amyloid connection now less relevant. Maybe.