Tag Archives: AD

Breakthrough In The Fight Against Alzheimer’s

Eisai Co.,  a company located in Tokyo, and Biogen Inc. in Cambridge, United States, announced positive topline results from the Phase II study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer’s disease. The study achieved statistical significance on key predefined endpoints evaluating efficacy at 18 months on slowing progression in Alzheimer’s Disease Composite Score (ADCOMS) and on reduction of amyloid accumulated in the brain as measured using amyloid-PET (positron emission tomography).

Study 201  is a placebo-controlled, double-blind, parallel-group, randomized study in 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or mild Alzheimer’s dementia (collectively known as early Alzheimer’s disease) with confirmed amyloid pathology in the brain. Efficacy was evaluated at 18 months by predefined conventional statistics on ADCOMS, which combines items from the Alzheimer’s Disease Assessment Scalecognitive subscale (ADAS-Cog), the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale and the Mini-Mental State Examination (MMSE) to enable sensitive detection of changes in early AD symptoms. Patients were randomized to five dose regimens, 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly and 10 mg/kg biweekly, or placebo.

Topline results of the final analysis of the study demonstrated a statistically significant slowing of disease progression on the key clinical endpoint (ADCOMS) after 18 months of treatment in patients receiving the highest treatment dose (10 mg/kg biweekly) as compared to placebo. Results of amyloid PET analyses at 18 months, including reduction in amyloid PET standardized uptake value ratio (SUVR) and amyloid PET image visual read of subjects converting from positive to negative for amyloid in the brain, were also statistically significant at this dose. Dose-dependent changes from baseline were observed across the PET results and the clinical endpoints. Further, the highest treatment dose of BAN2401 began to show statistically significant clinical benefit as measured by ADCOMS as early as 6 months including at 12 months.

Source: https://www.eisai.com/

New Hope To Fight Alzheimer’s

It is known that the onset of Alzheimer’s disease (AD) is associated with the accumulation of Amyloid beta () peptides in small molecular clusters known as oligomers. These trigger the formation of so-called ‘neurofibrillary tangles’ within neurons hamper their workings, ultimately causing cell death and so significant cognitive decline. Very large Aβ oligomers which form plaques outside neurons, alongside neuroinflammation have also been found to play a key part in the progression of the disease.


The EU-funded iRhom2 in AD project took as its starting point the protein iRhom2, which has been identified as a genetic risk factor for AD due to its pro-inflammatory properties. The team were able to explore further the influence of iRhom2 on neuroinflammation in mice. iRhom2 recently emerged as a protein of note in AD as it aids the maturation of an enzyme called TACE (tumor necrosis factor-α converting enzyme) guiding it towards a cell’s plasma membrane where the enzyme releases a cell-signalling cytokine (TNFα), implicated in the regulation of inflammatory processes. While mice studies have shown that TNFα-dependent inflammation can lead to sepsis and rheumatoid arthritis, it is also thought that the process contributes to neuroinflammatory signalling events, which can cause harm in the brain.

The EU-funded iRhom2 in AD project worked with mice that are prone to develop the hallmarks of AD, amyloid plaques and memory deficits. The team genetically altered iRhom2 in the mice then analysed the progression of the pathology using an array of biochemical and histological methods, together with a number of behavioural tests to assess cognitive decline. The results were somewhat surprising.

We initially hypothesised that iRhom2 would affect one specific aspect of neuroinflammation in AD. What we discovered was even more exciting as it actually affects several different aspects of neuroinflammation simultaneously. So modulating iRhom2 appears particularly well suited to interfere with AD,” explains project coordinator Prof. Dr. Stefan Lichtenthaler.

Source: https://cordis.europa.eu/