NIH, Medtronic-backed startup reports mixed Phase II deep brain stimulation data in Alzheimer's

The fornix, a bundle of nerve fibers in the brain--Courtesy of "BodyParts3D, The Database Center for Life Science licensed under CC Attribution-Share Alike 2.1 Japan"

Functional Neuromodulation, a startup backed by Medtronic ($MDT) and the National Institutes of Health, will advance its deep brain stimulation implant into a Phase III trial to treat Alzheimer's disease patients. DBS is a standard treatment for movement disorders, such as Parkinson's disease, but hasn't been widely applied to other brain disorders.

In the small Phase II ADvance trial, Functional Neuromodulation found that there was some clinical benefit to a subgroup of patients who were 65 and older. The trial was a randomized, double blind, placebo controlled trial of only 42 patients with an age of 45 to 85 who have mild Alzheimer's disease.

"The company is taking a unique approach to Alzheimer's disease by treating it as a disorder of the memory circuit that has become less active due to neuronal deterioration. By applying electrical impulses to the circuit, ADvance results suggest that DBSf may keep the memory circuit active," Dr. Anton Porsteinsson, a professor of psychiatry at the University of Rochester and a member of the independent data safety monitoring board for the study, said in a statement.

All patients received DBS implants that were used to stimulate or as a sham for 12 months; the system is applied to the fornix, a brain structure that connects the hippocampus, which is central to the consolidation of new memories, to other structures in the brain including the hypothalamus.

The 30 patient subgroup of older patients, with 15 patients in each of the sham and treatment arms, showed that treatment resulted in reduced cognitive decline after 12 months according to two different measures. However, the study wasn't adequately powered to achieve statistical significance for these groups on these measures: the Clinical Dementia Rating sum of boxes (CDR-SB) and the 12 item Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog 13).

The results did show a statistically significant change in glucose metabolism, which was shown to improve by roughly 20% to 22% but decline slightly in the placebo group. This change was statistically significant at 6 months and was maintained at 12 months.

"The results are encouraging," concluded Porsteinsson, "The study demonstrated an acceptable safety and a suggestion of clinical benefit in a subgroup of patients, which is supported by improvement in a biological marker. This approach clearly merits further clinical investigation."

The company expects to start enrollment in a Phase III trial of the DBSf program to treat Alzheimer's disease in mid-2016. It notes that there are currently 5 FDA-approved Alzheimer's disease treatments, but that they are of limited efficacy for about 6 to 12 months in around half of patients receiving them.

Functional Neuromodulation, based in Boston, MA, was founded in 2010 by Dr. Andres Lozano, a neurosurgery professor at the University of Toronto. He conducted a pilot study of DBS in 6 Alzheimer's patients with results published in the Annals of Neurology in October 2010.

Then in October 2011, the startup raised $10.4 million from Genesys Capital and Medtronic to back Phase II testing of DBS in mild Alzheimer's disease. Functional Neuromodulation also received a translational grant of up to $2.75 million to support the ADvance trial from the National Institute of Aging, which is part of the National Institutes of Health (NIH).

- here is the data announcement