One of the main venues of research in the fight against alzheimer’s disease is “plaque fighting” treatments. The “plaque” in this case are toxic proteins, called amyloid plaques that build up in Alzheimer’s patients’ brains. A team of researchers studied the clinical trial of a treatment using anducanumab—an antibody—on disrupting the amyloid plaque buildups in the patients brains. The results are very exciting.
The PRIME study shows that aducanumab penetrates the brain and decreases Aβ in patients with AD in a time- and dose-dependent manner. Within 54 weeks of treatment, 3, 6 and 10 mg kg−1doses of aducanumab significantly decreased the amyloid PET SUVR. Patients receiving placebo showed virtually no change in their mean PET SUVR composite scores over one year, indicating that Aβ pathology had already reached an asymptote of accumulation. Considering that it may have taken up to 20 years for Aβ to have accumulated to the levels in these patients at study entry, the observed kinetics of Aβ removal within a 12-month time period appears encouraging for a disease modifying treatment for patients with AD.
The cognitive results for CDR-SB and MMSE provide support for the clinical hypothesis that reduction of brain Aβ confers a clinical benefit. Post hoc analysis showed that those aducanumab-treated patients who had decreased SUVR scores >1 standard deviation unit relative to placebo-treated patients after one year of treatment experienced a stabilization of clinical decline on both CDR-SB and MMSE scores; whereas, those patients with a smaller or no decrease experienced clinical decline similar to placebo patients (Fig. 2c). The apparent clinical benefit observed in PRIME could also be explained by the binding of aducanumab to oligomeric forms of Aβ, which would not be directly detected by PET imaging. The reductions in SUVR scores may be surrogates for reductions in toxic soluble Aβ oligomers which may havehad a more functionally relevant impact on cognition. Whereas significant Aβ reduction was detectable by 6 months, clinical effects were not apparent until one year. Given that clearance of Aβ could be followed by recovery of neuronal function, a lag between reduction of Aβ burden and slowing of disease progression is not altogether surprising.
This is to say that the using the hypothesis that plaque buildup in Alzheimer’s may also be a part of the cause and not just the result of the disease, finding an antibody that is able to rid the patients’ brain of the toxic proteins may also be more than a treatment but something approaching a cure. Professor Roger Nitsch (Zurich University) who was a part of this research team:
“Compared to other studies published in the past, the effect size of this drug is unprecedented.”
Larger trials are already underway. At the very least, if this type of treatment even produces some positive results in slowing down of cognitive deterioration associated with Alzheimer’s disease, this would be a huge step forward.