Scientists from the Dominantly Inherited Alzheimer’s Network (DIAN) led by Stephen Salloway have found in a long-term observational study of 144 Alzheimer’s patients with familial disease that recombinant antibodies (gantenerumab and solanezumab) are unlikely to stop or prevent patients‘ cognitive decline. Because the manifestation of the hereditary variant of the disease, a specific form of Alzheimer’s called DIAD, occurs at a young age, but only one percent actually develop the disease despite a genetic predisposition, researchers have sought to determine the benefits of Alzheimer’s antibody therapy:
The study results, however, of the analysis that has been ongoing since 2008 are sobering. Analysis of the phase II-III trial found that neither gantenerumab (Roche) nor solanezumab (Eli Lilly) were properly effective. The beta-amyloid in the senile plaques in the brains of the patients could be reduced by the active substance gantenerumab – as well as other protein deposits such as tau proteins – but higher doses and a very early stage of the disease are probably necessary to treat the dominant familial dementia. Beta-amyloids, special proteins, are in fact considered the main trigger of the disease.
The participants in the study were 144 affected individuals, 52 of whom were treated with the recombinant antibodies gantenerumab and solanezumab, respectively. The rest of the patients, 40 in number, received only a placebo over an extended period of several years. The goal of therapy with the two genetically modified antibodies, which show immunological activity as proteins, is to sound out cognitive parameters in the first step. In the second step, changes in the downstream biomarkers are then recorded by monitoring. The spectrum ranges from clinical and cognitive parameters to imaging and biochemical ones.
The study’s conclusion so far is that the progression of the genetic variant of Alzheimer’s disease cannot currently be slowed or prevented.
However, the full potential of gantenerumab has not yet been conclusively determined because the drug showed amyloid-related abnormalities such as edema in 19.2 percent of cases in the gantenerumab group in imaging studies. However, many patients show no symptoms for a long time, meaning they are asymptomatic but already have deposits in the brain. Hence, experts consider higher doses over an even longer period.
Source: Pharmazeutische Zeitung