Pharmaceutical companies developing Alzheimer’s drugs have faced one hurdle after another. The most effective treatments are difficult to get into the brain, while those that show success in animals have yet to benefit humans.
Two startup companies aim to solve these problems by targeting the brain electrically rather than chemically. They’re both using technologies that have proven successful for other brain disorders. One company plans to use deep brain stimulation, which has been used to treat tens of thousands of Parkinson’s patients. The other hopes to find success with transcranial magnetic stimulation, a noninvasive approach used to treat depression and as a research tool to stimulate or inhibit specific parts of the brain.
In deep brain stimulation, electrical pulses are delivered to a dysfunctional part of the brain via a surgically implanted electrode, stimulating neural activity. The technology is being used or tested for a growing number of disorders, including medication resistant epilepsy, depression, and obsessive compulsive disorder. Neurosurgeon Andres Lozano, at the University of Toronto, became interested in its potential for treating Alzheimer’s thanks to an unexpected finding published in 2008. Researchers were testing to see if they could help a morbidly obese patient lose weight by stimulating a part of the brain that governs satiety. Follow-up tests revealed that the patient showed a significant improvement in memory.
Brain imaging revealed that the obesity treatment activated various brain structures involved in memory. Such structures have typically deteriorated in Alzheimer’s patients, and Lozano’s idea is to use deep brain stimulation to boost activity in the memory circuits that patients have left. Late last year, Lozano formed startup Functional Neuromodulation with Daniel O’Connell, founder of Neuroventures and now its CEO, to commercialize the technology.
It’s still unclear how well the approach will work in people with the neurodegenerative disorder. A small study published last fall showed mixed results. The treatment appeared to slow cognitive decline in a few patients, but had no effect in others. However, researchers did find that deep brain stimulation reversed one of the markers of Alzheimer’s: impaired glucose metabolism in the brain. Preliminary evidence suggests that it is more effective when used at earlier stages of the disease.
As with deep brain stimulation therapies for other conditions, the key to improving its effectiveness may lie in slight changes in the location of the stimulation, or in the electrical parameters used to stimulate the brain. Researchers are now doing animal studies to explore how deep brain stimulation triggers the release of chemicals involved in neuron growth and survival. (Some drug treatments now being studied for Alzheimer’s are designed to replace or boost these chemicals.) The company is also planning a larger study to be conducted at multiple centers across the country, O’Connell reported at a neurotechnology conference in San Francisco on Monday.
Another approach comes from Israeli startup Neuronix, which has developed a noninvasive treatment for Alzheimer’s based on transcranial magnetic stimulation. This method involves activating specific regions of the brain with targeted magnetic pulses. Neuronix targets the stimulation to specific brain regions and combines it with cognitive training tasks designed to activate those regions. For example, if the device targeted a region known as Broca’s area, which is involved in language, the patient would alternate between brain stimulation and word-related tasks on a computer screen.
In a clinical trial conducted in Israel in which patients underwent treatment for 45 minutes, five days a week for six weeks, researchers found that treated patients showed significant improvement in cognitive function compared to those given a sham treatment. Those improvements held steady during three months when patients underwent one to three treatments per week.
A year later, with no treatment, patients had deteriorated somewhat but were still much better than they were when they started, said Neuronix CEO Eyal Baror at the conference. The benefits are moderate—perhaps in line with cholinesterase inhibitors, the most common class of drugs now used to treat Alzheimer’s, which can alleviate some symptoms but do little to slow the progression of the disease. The device is already approved for use in Europe, and the company is now planning clinical trials in the United States.
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