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TORONTO—The fully human monoclonal antibody gantenerumab may reduce levels of neurogranin, a postsynaptic degradation marker specific to Alzheimer’s disease, according to a post hoc analysis described at the Alzheimer’s Association International Conference. Gantenerumab, however, does not affect levels of YKL-40, also known as chitinase-3-like protein 1, which is thought to be an inflammation marker mainly derived from astrocytes.
Philip Scheltens, MD, PhD, Director of the Alzheimer Center at the VU University Medical Center in Amsterdam, and colleagues conducted a trial to determine whether gantenerumab would influence dementia severity. The researchers screened people for prodromal Alzheimer’s disease by administering the Free and Cued Selective Reminding Test and measuring their level of CSF amyloid beta-42. They randomized 797 patients to placebo or to 105-mg or 225-mg doses of gantenerumab administered every four weeks by subcutaneous injection. CSF was collected at week 52 for some patients and at week 104 for all patients. A subset of 114 patients underwent amyloid PET. The trial’s primary end point was the Clinical Dementia Rating Scale Sum of Boxes. The study was halted after a futility analysis found no difference between treatment groups. 
During the study, the researchers measured levels of total tau, phospho tau, amyloid beta, neurogranin, and YKL-40. Post hoc analysis revealed that total tau tended to increase slightly in the placebo group, remain stable among patients receiving 105 mg of gantenerumab, and decline slightly among people receiving 225 mg of gantenerumab. Differences were significant at both time points.
At week 104, the investigators observed a significant decrease in phospho tau for both doses of gantenerumab. At the same time point, patients receiving the higher dose of gantenerumab had a decrease in neurogranin. “All three biomarkers showed a dose- and time-dependent decrease” following gantenerumab treatment, said Dr. Scheltens. Treatment did not affect levels of amyloid beta or YKL-40, however.
Among patients who underwent amyloid PET, the researchers observed a small and nonsignificant reduction in amyloid beta following treatment with gantenerumab. They noted a correlation between amyloid beta and phospho tau, but not between amyloid beta and total tau. “We do not exactly understand why that is the case,” said Dr. Scheltens.
“These biomarkers are … highly correlated among each other,” and this correlation is specific to Alzheimer’s disease, he added. Patients with Creutzfeldt–Jakob disease or stroke may have large increases in total tau, but not in phospho tau or neurogranin. Furthermore, neurogranin is not elevated in other neurodegenerative diseases such as frontotemporal dementia or dementia with Lewy bodies. “This is a characteristic pattern,” said Dr. Scheltens.
A higher dose of gantenerumab may reduce levels of amyloid beta, and further study of the therapy is needed, Dr. Scheltens concluded.
—Erik Greb
Suggested Reading
Bohrmann B, Baumann K, Benz J, et al. Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. J Alzheimers Dis. 2012;28(1):49-69.
Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69(2):198-207.
Panza F, Solfrizzi V, Imbimbo BP, et al. Efficacy and safety studies of gantenerumab in patients with Alzheimer’s disease. Expert Rev Neurother. 2014;14(9):973-986.
TORONTO—The fully human monoclonal antibody gantenerumab may reduce levels of neurogranin, a postsynaptic degradation marker specific to Alzheimer’s disease, according to a post hoc analysis described at the Alzheimer’s Association International Conference. Gantenerumab, however, does not affect levels of YKL-40, also known as chitinase-3-like protein 1, which is thought to be an inflammation marker mainly derived from astrocytes.
Philip Scheltens, MD, PhD, Director of the Alzheimer Center at the VU University Medical Center in Amsterdam, and colleagues conducted a trial to determine whether gantenerumab would influence dementia severity. The researchers screened people for prodromal Alzheimer’s disease by administering the Free and Cued Selective Reminding Test and measuring their level of CSF amyloid beta-42. They randomized 797 patients to placebo or to 105-mg or 225-mg doses of gantenerumab administered every four weeks by subcutaneous injection. CSF was collected at week 52 for some patients and at week 104 for all patients. A subset of 114 patients underwent amyloid PET. The trial’s primary end point was the Clinical Dementia Rating Scale Sum of Boxes. The study was halted after a futility analysis found no difference between treatment groups.
During the study, the researchers measured levels of total tau, phospho tau, amyloid beta, neurogranin, and YKL-40. Post hoc analysis revealed that total tau tended to increase slightly in the placebo group, remain stable among patients receiving 105 mg of gantenerumab, and decline slightly among people receiving 225 mg of gantenerumab. Differences were significant at both time points.
At week 104, the investigators observed a significant decrease in phospho tau for both doses of gantenerumab. At the same time point, patients receiving the higher dose of gantenerumab had a decrease in neurogranin. “All three biomarkers showed a dose- and time-dependent decrease” following gantenerumab treatment, said Dr. Scheltens. Treatment did not affect levels of amyloid beta or YKL-40, however.
Among patients who underwent amyloid PET, the researchers observed a small and nonsignificant reduction in amyloid beta following treatment with gantenerumab. They noted a correlation between amyloid beta and phospho tau, but not between amyloid beta and total tau. “We do not exactly understand why that is the case,” said Dr. Scheltens.
“These biomarkers are … highly correlated among each other,” and this correlation is specific to Alzheimer’s disease, he added. Patients with Creutzfeldt–Jakob disease or stroke may have large increases in total tau, but not in phospho tau or neurogranin. Furthermore, neurogranin is not elevated in other neurodegenerative diseases such as frontotemporal dementia or dementia with Lewy bodies. “This is a characteristic pattern,” said Dr. Scheltens.
A higher dose of gantenerumab may reduce levels of amyloid beta, and further study of the therapy is needed, Dr. Scheltens concluded.
—Erik Greb
Suggested Reading
Bohrmann B, Baumann K, Benz J, et al. Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. J Alzheimers Dis. 2012;28(1):49-69.
Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69(2):198-207.
Panza F, Solfrizzi V, Imbimbo BP, et al. Efficacy and safety studies of gantenerumab in patients with Alzheimer’s disease. Expert Rev Neurother. 2014;14(9):973-986.
TORONTO—The fully human monoclonal antibody gantenerumab may reduce levels of neurogranin, a postsynaptic degradation marker specific to Alzheimer’s disease, according to a post hoc analysis described at the Alzheimer’s Association International Conference. Gantenerumab, however, does not affect levels of YKL-40, also known as chitinase-3-like protein 1, which is thought to be an inflammation marker mainly derived from astrocytes.
Philip Scheltens, MD, PhD, Director of the Alzheimer Center at the VU University Medical Center in Amsterdam, and colleagues conducted a trial to determine whether gantenerumab would influence dementia severity. The researchers screened people for prodromal Alzheimer’s disease by administering the Free and Cued Selective Reminding Test and measuring their level of CSF amyloid beta-42. They randomized 797 patients to placebo or to 105-mg or 225-mg doses of gantenerumab administered every four weeks by subcutaneous injection. CSF was collected at week 52 for some patients and at week 104 for all patients. A subset of 114 patients underwent amyloid PET. The trial’s primary end point was the Clinical Dementia Rating Scale Sum of Boxes. The study was halted after a futility analysis found no difference between treatment groups.
During the study, the researchers measured levels of total tau, phospho tau, amyloid beta, neurogranin, and YKL-40. Post hoc analysis revealed that total tau tended to increase slightly in the placebo group, remain stable among patients receiving 105 mg of gantenerumab, and decline slightly among people receiving 225 mg of gantenerumab. Differences were significant at both time points.
At week 104, the investigators observed a significant decrease in phospho tau for both doses of gantenerumab. At the same time point, patients receiving the higher dose of gantenerumab had a decrease in neurogranin. “All three biomarkers showed a dose- and time-dependent decrease” following gantenerumab treatment, said Dr. Scheltens. Treatment did not affect levels of amyloid beta or YKL-40, however.
Among patients who underwent amyloid PET, the researchers observed a small and nonsignificant reduction in amyloid beta following treatment with gantenerumab. They noted a correlation between amyloid beta and phospho tau, but not between amyloid beta and total tau. “We do not exactly understand why that is the case,” said Dr. Scheltens.
“These biomarkers are … highly correlated among each other,” and this correlation is specific to Alzheimer’s disease, he added. Patients with Creutzfeldt–Jakob disease or stroke may have large increases in total tau, but not in phospho tau or neurogranin. Furthermore, neurogranin is not elevated in other neurodegenerative diseases such as frontotemporal dementia or dementia with Lewy bodies. “This is a characteristic pattern,” said Dr. Scheltens.
A higher dose of gantenerumab may reduce levels of amyloid beta, and further study of the therapy is needed, Dr. Scheltens concluded.
—Erik Greb
Suggested Reading
Bohrmann B, Baumann K, Benz J, et al. Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. J Alzheimers Dis. 2012;28(1):49-69.
Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69(2):198-207.
Panza F, Solfrizzi V, Imbimbo BP, et al. Efficacy and safety studies of gantenerumab in patients with Alzheimer’s disease. Expert Rev Neurother. 2014;14(9):973-986.
