Oligosaccharide binds better to amyloid-β than monoclonal antibodies, and enhanced clearance of the protein from the brain, improving cognition in Alzheimer's disease, according to Chinese researchers.
The study, which was presented at the 7th Clinical Trials Conference on Alzheimer’s Disease, tested the safety and efficacy of oligomannurarate (GV-971, Shanghai Greenvalley Pharmaceutical Company) in a double-blind, placebo-controlled phase II trial in patients with mild to moderate Alzheimer’s disease.
Monoclonal antibodies have previously been used to bind sites of amyloid-β, but no efforts have been able to change the disease course.
Oligomannurarate targets multiple sites of amyloid-β, and so the researchers, including Shifu Xiao, MD, PhD, from Shanghai Jiao Tong University School of Medicine in China, and colleagues, hypothesized that it would inhibit amyloid-β aggregation and have lower neurotoxicity.
Men and women aged 50 to 85 years with confirmed Alzheimer’s disease and Mini-Mental State examination scores of 10 to 24 were given either 600 mg/day or 900 mg/day of oligomannurarate or placebo for six months. At 24 weeks, the 900 mg/day group showed a trend towards improved cognitive scores.
Upon evaluation of cerebrospinal fluid of patients receiving the 600 mg/day or 900 mg/day doses at 24 weeks, the 900 mg/day group had increased levels of amyloid-β1-42, suggesting a clearance of amyloid from the brain into the cerebrospinal fluid.
Overall, the treatment was safe and well tolerated, and the researchers plan to now continue with the 900 mg/day dose in a phase III trial.
Shooting at the same target but with a different kind of arrow, Chinese researchers have shown that an oligosaccharide that binds more than one region of amyloid-β (Aβ) enhances clearance of the protein from the brain and improves cognition among patients with mild to moderate Alzheimer’s disease (AD).
“Family members perceived improvements after 24 weeks [of] treatments,” Shifu Xiao, MD, PhD, from Shanghai Jiao Tong University School of Medicine in China told attendees here at the 7th Clinical Trials Conference on Alzheimer’s Disease (CTAD).