Functional Neuromodulation has initiated the ADvance study in the USA and Canada to assess deep brain stimulation (DBS) in patients with mild Alzheimer’s disease. ADvance will evaluate the safety and potential clinical benefit of DBS of the fornix (DBS-f), a major inflow and output pathway in the brain’s memory circuit. Research suggests this is an area affected early in the development of Alzheimer’s. The first ADvance patient enrolled has been successfully implanted.
ADvance is a randomised double-blind controlled trial initially involving 20 people aged 55-80 with mild Alzheimer’s disease. The trial will compare the effects of DBS turned on to those observed with the system turned off. The patients will undergo regular physiological, psychological and cognitive assessments for 12 months at which time those patients in the off group will be eligible to have the system activated. Brain imaging measures of changes in glucose metabolism and the size of key structures involved in memory will also be assessed at multiple time points.
The study is co-chaired by Andres Lozano, RR tasker chair in Stereotactic and Functional Neurosurgery at the University Health Network and University of Toronto and scientific founder of the company; and Constantine Lyketsos, Elizabeth Plank Althouse professor, Johns Hopkins University, and director, Johns Hopkins Memory and Alzheimer’s Treatment Center.
The study is currently recruiting patients at Toronto Western Hospital, Johns Hopkins Bayview Medical Center, the Banner Alzheimer’s Institute in Phoenix, and the University of Florida Center for Movement Disorders and Neurorestoration. The study is under institutional review for participation at a few additional leading Alzheimer’s clinical research centres in the USA.
ADvance is informed by a pilot study of DBS-f in six Alzheimer’s patients conducted at Toronto Western Hospital by Lozano and his team. A follow-up paper evaluating the relationship between brain metabolism and clinical outcomes in that study was recently published in Archives of Neurology. That publication reported increased glucose metabolism in key brain networks after stimulation, indicating an increase in neuronal activity and better functional connectivity in areas affected by Alzheimer’s. At one year, this increase in brain metabolism correlated with better outcomes in cognition, memory and quality of life.
“DBS-f delivers stimulation to a critical location in the brain’s memory circuit that seems to enhance activity in the circuit and drive neuronal activity in other brain regions impacted by Alzheimer’s. ADvance will enable us to assess further whether stimulating the brain with DBS-f can drive neural activity in a way that might lead to better clinical outcomes,” said Lyketsos, ADvance national co-chair.
“As people are increasingly aware, there is an urgent need for new and better ways to treat Alzheimer’s. DBS is a promising new approach that has a successful track record in a number of other brain disorders,” said Dan O’Connell, Functional Neuromodulation co-founder and CEO. “We have worked closely with a stellar group of scientific, clinical and regulatory experts to design ADvance as a feasibility study to determine if DBS-f could constitute a new circuitry-based approach to treating this devastating disease. We look forward to expanding the study to more leading Alzheimer’s centres in the USA.”