More Evidence That Prions Cause Alzheimer’s Disease
ProMIS Neurosciences highlighted the growing mountain of research, which calls out Amyloid-beta and Tau prions (proteins), as the root cause for Alzheimer’s disease. The company released a white paper today compiling the scientific data as the basis for new treatments.
In the white paper, the company provided a concise overview of empirical evidence from a number of leading researchers, much of it recent, that supports the methodology of selectively targeting the prion variants of Amyloid-beta and Tau.
Amyloid-beta (Aβ) acts as a causative agent in the progression of Alzheimer’s disease. Researchers also have discovered that depletion of Aβ reversed cerebral amyloidosis and associated pathology in susceptible mice.
Other research points to the likelihood that prion-like oligomers of misfolded Aβ mediate neurotoxicity and progression of Alzheimer’s disease. In the Cleary et al 2004; Jin et al 2011 studies, scientists concluded that while the presence of Aβ plaque was the calling card of Alzheimer’s disease, the synaptic loss and neurodegenerative spread of the disease were primarily mediated by soluble oligomers of misfolded Aβ rather than plaque.
Even more research contends that the progressive nature of Alzheimer’s disease comes from the formation and spread of Aβ prions. As found in the Khan et al 2014 study, the self-propagation of these Aβ prions follows the stereotypical progression of AD. The prion-like spread is well-documented in animal models.
A growing body of data also indicates that the selective targeting of Aβ prions offers distinct advantages over the broadly reactive Aβ antibodies currently in clinical testing. This specificity of Aβ prion neutralization is expected to increase efficacy by mitigating “target distraction.” This means that treating physicians can preserve normal Aβ function in the patient as well as decreasing the risk of edema and vascular adverse effects.
To achieve this precision medicine approach to Alzheimer’s therapy, ProMIS employed two proprietary computational discovery technologies, ProMIS™ and Collective Coordinates to predict regions of protein most likely to unfold based on thermodynamic stability. This means the company was able to identify six predicted disease-specific epitopes of Aβ prions that would act as homing beacons for antibody therapy. Antibodies have been raised from five of the epitopes and are currently undergoing screening and validation for prion-specific binding and functional activity.