For Researchers > Clinical Research at Farber > Center for Alzheimer's Disease Research and Care > Anti-Amyloid Therapy for Hemorrhagic Stroke And Cerebral Amyloid Angiopathy

• Barry Rovner, M.D. Lead Farber Investigator
• Rodney Bell, M.D., Co-Principal Investigator Co-Investigator
• Steven M. Greenberg, M.D., Ph.D., Harvard Medical School/Massachusetts General Hospital, Principal Investigator for Multi-Center Trial

There is no known therapy for Cerebral Amyloid Angiopathy (CAA), an important cause of hemorrhagic stroke and other clinical syndromes in the elderly. The pathologic basis of CAA-related stroke is deposition of the amyloid beta peptide (a-beta) in cerebral vessels, and resultant degeneration of the vessel wall. We were one of five sites engaged in a phase 2 pilot study investigating the safety, tolerability, and preliminary efficacy of Cerebril for secondary prevention of recurrent CAA-related intracerebral hemorrhage. Cerebril is a small molecule designed to compete with glycosaminoglycans for binding to a-beta.

Preliminary studies have demonstrated that this compound penetrates to the CNS, inhibits a-beta fibril formation and a-beta-induced cellular toxicity, and reduces severity of CAA in a transgenic mouse model without evidence of major intrinsic toxicity. Participants were survivors of lobar hemorrhagic stroke, who are considered at high-risk for recurrence based on baseline gradient-echo MRI scan or apolipoprotein-E genotype. Patients were randomized to receive a daily dose of either 100, 200, or 300 mg of Cerebril, for a 16-month period, and were followed for adverse clinical events, laboratory abnormalities, and recurrent stroke or decline in cognitive, functional, or neurologic status. At 8 and 16 months of treatment, subjects underwent follow-up MRI scans to determine the appearance of new hemorrhagic lesions during treatment. In addition to testing a promising agent for CAA, the study has generated infrastructure organization and pilot data to serve as a springboard for future trials of emerging anti-amyloid treatments.

Preliminary data on 24 CAA patients with lobar cerebral hemorrhage who received one of the three dose regiments for 12 weeks were reported in April 2004. The data showed no safety findings of concern based on patient's clinical laboratory tests, vital signs and electrocardiograms during follow-up of physical exams. The most frequent adverse events, namely nausea and vomiting, were mild to moderate at all doses tested, and transient in the patients receiving 100 mg or 200 mg daily of Cerebril. Five patients withdrew prematurely, three due to nausea and vomiting and two because of expected complications of CAA.

A phase 3 trial of Cerebril is expected to be initiated soon.

The trial is being supported in part by NINDS. Neurochem, based in Laval, Canada, is developing Cerebril.