Top 10 Alzheimer’s Disease Stories of 2019
We look forward to bringing the same quality of coverage to those living with Alzheimer’s in the coming year. Here are the 10 most-read stories of 2019, with brief summaries of what made each one relevant to the Alzheimer’s community.
Genentech began enrolling patients into a Phase 2 trial (NCT03828747) to measure how an experimental compound called RO7105705 affects cognitive function and functional abilities in Alzheimer’s patients over a 49-week period. The compound is a humanized monoclonal antibody designed to prevent toxic forms of tau protein from spreading between cells within the brain. The spread of tau protein is known to hasten the onset and progression of cognitive decline in Alzheimer’s disease. Given Tau’s central role in Alzheimer’s, several other anti-Tau drug trials are underway, including another Phase 2 trial run by Genentech (NCT03289143), a Phase 1b/2a trial of an anti-Tau vaccine, and early-stage trials of Tau aggregation blockers.
A modified Mediterranean-ketogenic diet can regulate bacteria in the gut that may contribute to the development and progression of cognitive impairment and Alzheimer’s disease, according to a recent pilot study (NCT02984540). Among 17 study participants, the Mediterranean diet led to unique microbial patterns in 11 patients with mild cognitive impairment, which corresponded with reduced levels of tau protein and beta-amyloid molecules. “Determining the specific role these gut microbiome signatures have in the progression of Alzheimer’s disease could lead to novel nutritional and therapeutic approaches that would be effective against the disease,” said Hariom Yadav, PhD, one of the study’s coauthors.
An antiviral medicine may help halt the decline of cognitive function in Alzheimer’s patients who are positive for a herpes simplex virus, according to preliminary results from a Phase 2 trial (NCT02997982). A previous study showed a link between herpes simplex virus type 1 (HSV1) and Alzheimer’s disease, which suggested that anti-herpes medications such as valacyclovir, also known as Valtrex, may help Alzheimer’s patients. Over a four-week period, valacyclovir was given to 36 patients with early Alzheimer’s disease, who had markers of HSV infection and carried a variant of the apolipoprotein E gene (APOE-ε4) that’s associated with a higher risk of early Alzheimer’s. Results from the first 10 patients to complete the trial showed improvements in cognitive function with no reported side effects. These encouraging results merit larger placebo-controlled follow-up studies, the researchers said.
A potential vaccine against a key protein in Alzheimer’s disease progression was found to be safe and well-tolerated among patients in a Phase 2a clinical trial (NCT02551809). The vaccine candidate, called UB-311, triggers an immune response against beta-amyloid, which accumulates in the brains of Alzheimer’s patients, without causing potentially dangerous inflammation. Preliminary data indicated that the vaccine could stabilize patients’ cognitive abilities and behavioral functions. Because this study consisted of only 43 patients, these benefits showed no statistical significance.
Patients from this study were eligible to participate in a Phase 2 extension study (NCT03531710) to evaluate the long-term safety, tolerability, and potential efficacy of UB-311. However, the study was terminated, following a review of baseline data and an error in treatment assignment.
Two Phase 3 trials evaluating a potential antibody against beta-amyloid had to be discontinued, due to a lack of evidence that it would successfully halt dementia progression in Alzheimer’s patients. Crenezumab was designed to target beta-amyloid, a key driver of Alzheimer’s disease, and to reduce inflammation in the brain, which is a severe side effect of beta-amyloid immunotherapy for Alzheimer’s disease. Although these two trials — CREAD 1 (NCT02670083) and CREAD 2 (NCT03114657) — had to be stopped, crenezumab is being investigated in the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease trial (NCT01998841). Meanwhile, Genentech continues to conduct two Phase 3 trials for gantenerumab, which targets beta-amyloid, and the Phase 2 TAURIEL trial of RG6100 (NCT03289143), which targets several species of tau protein.
Yerba santa, a plant native to California, holds neuroprotective and anti-inflammatory potential for Alzheimer’s disease, according to one study. A team from the Salk Institute for Biological Studies discovered that a compound within yerba santa, called sterubin, prevented cells from dying of oxytosis — a process in which cells die from an inability to protect themselves against reactive oxygen species (harmful agents responsible for a phenomenon called oxidative stress).
Oxytosis is linked to age-related neurodegeneration, which is found in Alzheimer’s and other diseases of the central nervous system. Sterubin prevented the production of reactive oxygen species in nerve cells by stabilizing glutathione levels. Furthermore, sterubin increased levels of Nrf2 and ATF4, important regulators of nerve cell metabolism and function. “[W]e believe that sterubin deserves further examination in the context of Alzheimer’s disease, as well as other neurodegenerative diseases,” the Salk team wrote.
“The light goes off in your brain and you don’t know what is going to happen,” journalist Greg O’Brien said about his experience living with Alzheimer’s disease. In 12 conversations recorded over a three-year period, O’Brien shares his insights about life and Alzheimer’s with David Shenk, who’s written extensively about the disease. Raw, touching, and deeply engaging, the two men delve into the realities of living with Alzheimer’s on their podcast, called The Forgetting. “You can hear the difference from one episode to the next,” Shenk said. “There is a real benefit to having recorded this over a period of time. We wanted to show the progression of the disease until we can’t do so anymore.” Listen to The Forgetting via WCAI’s website, iTunes, Stitcher, and Facebook.
Researchers have found evidence to link a bacteria to Alzheimer’s disease upon discovering Porphyomonas gingivalis, a bacteria that causes the gum disease known as chronic periodontitis, in the brains of Alzheimer’s patients. P. gingivalis releases toxic enzymes called gingipains, which cause tau proteins to crumble into the insoluble fragments that contribute to Alzheimer’s progression. The study found that gingipains were toxic to neurons in cell culture and in mice, and that certain compounds effectively blocked gingipain production. One such compound, called COR388, is being tested in a Phase 1 trial (NCT03331900).
Carrots won’t improve night-time vision, but, together with green tea, they might prove useful in treating Alzheimer’s disease. A recent study showed that compounds within the two plants reversed cognitive deficits, lowered the accumulation of toxic amyloid beta, and reduced brain inflammation and oxidative cell damage in mice. EGCG, found in green tea, crosses the blood-brain barrier to reduce the levels of amyloid beta. Ferulic acid, found in carrots, functions as both an anti-inflammatory and antioxidant. Administered together to mice, they effectively restored spatial working memory, along with several other measures of cognitive function. If the same results hold true for humans, the compounds would enable a therapy that can be brought rapidly to market, because rather than having “to wait 10 to 12 years for a designer drug (…) you can make these dietary changes today,” said the study’s senior author Terrence Town, PhD, a researcher at the University of Southern California.
At Alzheimer’s News Today, we hope these stories and our reporting throughout this year help to better inform and improve the lives of everyone affected by Alzheimer’s.
We wish all our readers a happy 2020.