Throughout 2018, Alzheimer’s News Today brought you stories of important discoveries, treatment developments, clinical trials, and other events related to Alzheimer’s disease.
As we look forward to providing more news to those living with Alzheimer’s as well as their family members and caregivers this year, here are the 10 most-read stories of 2018.
No. 10 — “Phase 3 Trials of Gantenerumab Likely to Decide Clinical Benefit, Roche Says in Interview”
In an interview with Alzheimer’s News Today, Rachelle Doody, MD, Roche’s global head of neurodegeneration, talked about the clinical development of Roche’s amyloid-targeting antibody candidate, called gantenerumab, for early — prodromal — Alzheimer’s. While a clinical trial in 2014 was discontinued because data showed no improvements in cognition or function with gantenerumab over a placebo, a thorough analysis of data collected since 2010 showed that the therapy at higher doses could lower the levels of aggregated beta-amyloid, the main component of the senile plaques characteristic of Alzheimer’s.
Following early studies in Alzheimer’s disease that showed the active component of aspirin, called acetylsalicylic acid, could improve cognitive functions and reduce the incidence of Alzheimer’s disease, researchers investigated the mechanism behind this protection. In this study, they showed that low-dose aspirin boosts the clearance of amyloid plaques, a hallmark of Alzheimer’s disease, by promoting its uptake and destruction in newly produced lysosomes — small vesicles essential for cellular waste destruction.
No. 8 — “Merck Stops Phase 3 Trial of Verubecestat in Early Alzheimer’s Patients Amid Concerns Over Benefit”
The search for an Alzheimer’s treatment has been hampered by setbacks, including one in February 2018 when, following a recommendation by an external data monitoring committee, Merck decided to stop its Phase 3 clinical study testing verubecestat (MK-8931) in patients with early-stage Alzheimer’s disease. The APECS study (NCT01953601) was testing the safety and efficacy of verubecestat in prodromal Alzheimer’s patients, but the trial was stopped because of concerns about the therapy’s benefits after analyzing data compiled at the time. At the same time, however, Biogen announced the recruitment of more patients to its two Phase 3 studies — EMERGE (NCT02484547) and ENGAGE (NCT02477800) — testing aducanumab (BIIB037), a potential therapy to decrease amyloid plaques in early Alzheimer’s patients.
No. 7 — “Bryostatin-1 Can Reverse Cognitive Decline in Moderate-to-Severe Alzheimer’s, New Data Shows”
Adding to the many possible treatments being investigated for Alzheimer’s, Neurotrope reported how its candidate therapy Bryostatin-1 may potentially help reverse cognitive decline in patients with moderate to severe Alzheimer’s. This benefit was sustained for at least four weeks after the treatment ended and was even more pronounced in the absence of the therapy memantine (sold in the U.S. as Namenda and Namzaric). The results prompted a new Phase 2 trial (NCT03560245), which is currently recruiting participants, to confirm the benefits of bryostatin.
No. 6 — “Roche Set to Start Two Phase 3 Trials of Gantenerumab in People with Early to Mild Alzheimer’s”
After a long research process that defined gantenerumab’s optimal dose, Roche launched two Phase 3 trials to test the antibody’s efficacy in people with early to mild Alzheimer’s. The trials — GRADUATE1 (NCT03444870) and GRADUATE2 (NCT03443973) — will run for two years at sites across the U.S., Canada, Europe, South America, Australia, and Asia. Both trials are currently recruiting participants to confirm early data showing the likelihood of “very good reductions of amyloid at the higher dose,” Rachelle Doody, MD, Roche’s global head of neurodegeneration, said in an interview with Alzheimer’s News Today.
No. 5 — “Saving Brain Connections by Targeting Synaptic Proteins May Treat Alzheimer’s, Study Finds“
Researchers at the Karolinska Institutet in Sweden reported how proteins in nerve cell synapses — the junctions between two nerve cells that allow them to communicate — are abnormal in the brains of patients with Alzheimer’s disease, correlating with the rate of cognitive decline. The findings support the therapeutic targeting of synaptic proteins as a potential strategy for early disease intervention.
In an example of how approved therapies for certain diseases may carry broader benefits to diseases without effective treatment, Canada’s IntelGenx launched a Phase 2a proof-of-concept trial to evaluate whether the old asthma medication montelukast may be an option for treating Alzheimer’s disease. The study (NCT03402503) is currently recruiting, and stems from research showing that montelukast halts inflammation, driven by factors called leukotrienes, and boosts generation of nerve cell progenitors — those that ultimately give rise to neurons.
Early data from the Phase 1b PRIME trial (NCT01677572) showed how long-term use of Biogen’s aducanumab — an antibody targeting beta-amyloid aggregates — may help prevent progression of Alzheimer’s in patients in the early stages of the disease. Biogen is currently evaluating the effectiveness and safety of aducanumab in early Alzheimer’s disease in two Phase 3 trials, ENGAGE (NCT02477800) and EMERGE (NCT02484547).
While most Alzheimer’s research focuses on the brain, the gut microbiome is increasingly seen as a key player in serious and chronic neurodegenerative diseases. In this study, researchers proposed a term — “mapranosis” — to capture the process by which amyloid proteins produced by certain gut microbes can modify the structure of amyloid proteins in the brain produced by neurons, leading to inflammation in the central nervous system. These findings support research on a gut-brain communication axis and how understanding its intricate and delicate interactions may lead to therapies for Alzheimer’s and other neurodegenerative diseases.
Japanese authorities formally approved the first stem cell therapy for the treatment of mild to moderate Alzheimer’s patients. The therapy, developed by the biotech company Nature Cell and the Biostar Stem Cell Research Institute, both based in South Korea, uses stem cells extracted from patients’ own (autologous) fat (adipose) tissue, which are expanded in the laboratory until they reach high numbers, and injected back into patients’ blood. “With the start of stem cell treatment, Biostar will support Alzheimer’s patients from all over the world — including Japan, Korea, China, and the U.S., starting in Japan — to restore their memory and ultimately their humanity,” said Jeong-Chan Ra, the lead investigator of the team who developed the therapy.
Alzheimer’s News Today hopes that the information we provide in 2019 will educate, inform, and improve the lives of patients with Alzheimer’s and their loved ones.
We wish all our readers a happy and inspiring 2019.