In Need of Brain Breakthroughs

Several years ago, when Kim Spletter began experiencing stiff muscles and difficulty walking, she chalked it up to her exercise regimen. Yet even after she'd scaled her workouts back, the symptoms continued to worsen. Soon Spletter, who lives in Frederick, Maryland, was experiencing tremors in her left leg and muscle rigidity. When doctors ultimately diagnosed the retired Montgomery County sheriff, who was then 45, with Parkinson's disease, she was devastated.

Then last year, her physician encouraged Spletter to participate in a new clinical trial at the University of Maryland Medical Center that would target and heat the brain cells interfering with her motor skills. Over the course of four hours, Spletter received a series of focused ultrasound waves applied through her skull. After the 11th wave, she'd regained 70 percent of her strength on the side of her body affected by her condition.

"The results were instantaneous," says Spletter nearly a year after the treatment. "I feel like I've been given a second chance. I'm biking, running and even teaching an indoor cycling class specifically designed for people with Parkinson's."

As aging Baby Boomers usher in what is expected to be a "silver tsunami" of neurodegenerative disease, researchers are working urgently to speed up the search for more effective treatments, if not cures. At the moment, 1 million Americans have Parkinson's, and by 2030 that number is expected to jump by 80 percent. The Alzheimer's Association predicts that the number of Americans 65 and older suffering from the devastating brain disorder will almost triple to 13.8 million by 2050. A national effort known as the BRAIN Initiative (for Brain Research through Advancing Innovative Neurotechnologies) was launched by the White House in 2013 to unlock the mysteries of the brain by developing tools to examine how "individual brain cells and complex neural circuits interact at the speed of thought." Scientists hope that this sort of brain "mapping" could lead to better answers not only for people with Alzheimer's and Parkinson's but also with brain tumors, depression, multiple sclerosis and other neurological conditions. Meantime, here are a few promising updates from the brain research front lines:

Progress Against Parkinson's Disease

The best that medicine can do at the moment to fight Parkinson's, a disorder in which the motor cells stop communicating properly due to a lack of the neurotransmitter dopamine, is to control the symptoms: tremors, stiffness, difficulty with walking and balance, depression and dementia. Current treatments generally rely on drugs that replace or act like dopamine. When drugs don't suffice or side effects interfere, a surgical procedure known as deep brain stimulation can sometimes be helpful. DBS therapy involves drilling a hole in the skull and inserting a thin electrode to target motor circuits that an MRI can identify as not functioning properly. Electrical pulses from a device similar to a cardiac pacemaker, implanted under the skin of the abdomen or near the collarbone, stimulate the brain region and block nerve signals that cause symptoms.

The focus of research lately has been on less invasive ways to improve quality of life, as well as on the continued quest for medications that slow the rate at which Parkinson's progresses. (Some drugs that look promising are currently in clinical trials, as is gene therapy.) The procedure performed on Spletter, focused ultrasound guided by MRI, creates a heat lesion at a targeted neural circuit that essentially resets the damaged circuit. The patient is awake and monitored in real time so that doctors can precisely aim the beam and conduct physical tests to see if symptoms are fading.

It's known that focused ultrasound can make Parkinson's symptoms less debilitating, says Dr. Howard Eisenberg, principal investigator and a neurosurgeon at the University of Maryland Medical Center. "What we don't know yet is how long the results will last. Kim was our first patient," he says, and she is "doing great." It's still too early in testing to know if the treatment could be repeated.

Spletter, who arrived for the procedure in a wheelchair and walked out without assistance, says she's been given a new lease on life. "I am hoping the focused ultrasound treatment will last long enough for researchers to find a cure or improve the current medications," she says.

[See: 5 Ways to Cope With Mild Cognitive Impairment.]

New Approaches to Tackling Deadly Brain Tumors

Treating brain cancer is a notoriously difficult matter. Drugs are often blocked by the blood-brain barrier; surgery carries the risk of damaging tissue responsible for vital functions. For inoperable tumors, radiation is often the answer, but it, too, can damage healthy tissue. And at a certain point a maximum dose may be reached.

One tack doctors are taking when tumors recur or can't be safely accessed through standard surgery is applying heat -- in this case generated by a laser -- to kill rogue cells. Although laser treatment for cancer isn't new, the technology has advanced, allowing greater precision. And in contrast to radiation, repeating the procedure is sometimes an option. Guided by MRI, doctors thread a laser catheter about the size of a pencil lead through a small opening in the skull and into the center of a tumor.

"Traditionally, brain surgery has been a very intensive procedure, requiring multiple night stays, hours of surgery and postoperative recovery time," says Dr. Julian Bailes, chair of the department of neurosurgery and co-director of the Northshore Neurological Institute at Northshore University HealthSystem in Chicago. The laser procedure "only requires an incision the size of a coffee stirrer, one stitch, and an overnight hospital stay." He and his colleagues are among the first in the country to use the MRI-guided laser system Visualase to treat inoperable tumors including glioblastoma and high-grade gliomas and metastases to the brain from elsewhere. A similar device, NeuroBlate, is being used at the Cleveland Clinic and other hospitals.

While the data on how patients fare is still extremely limited, Bailes says the outcomes he is seeing are very encouraging; early results are showing the procedure can extend lives, even if only by weeks or months.

Will the promise of immunotherapy, which is now being used to treat lung cancer, melanoma and leukemia, extend to brain cancer? A number of approaches enlisting the immune system are being tried, including one against glioblastoma that removes the patient's T cells, engineers them to attack the tumor and reinfuses them.

And a treatment developed by researchers at Duke University was recently designated a "breakthrough therapy" by the Food and Drug Administration for its success attacking glioblastoma through the injection of a modified poliovirus directly into the tumor. The virus infects the tumor, signaling the immune system that it is an enemy. A phase one clinical trial showed a 22 percent three-year survival rate, compared to the normal 4 percent rate. The first two patients, who were treated in 2012, are still cancer-free. The breakthrough designation means the FDA will expedite getting the treatment developed and approved.

[See: Emerging Treatments for Alzheimer's Disease.]

Attacking Alzheimer's Before Symptoms Arise

It's long been thought that a buildup of amyloid beta protein, which accumulates outside nerve cells and begins to block communication between neurons, is largely responsible for the ravages of this disease. All people naturally produce the protein, and a May study from Massachusetts General Hospital adds evidence that it may even play a role in the immune system, protecting the brain against pathogens. But certain genetic and environmental factors may contribute to some people's handling the protein poorly.

This theory of the disease has focused efforts on finding effective anti-amyloid agents. Those that have reached the testing stage so far have worked only modestly and not well enough to impress the FDA. Researchers now think that's because amyloid beta begins to do its harm, damaging brain cells' synapses, long before the characteristic plaques form and symptoms are distinguishable. And drugs to date have only been tested in people who already have symptoms. Current medications for Alzheimer's may ease symptoms for a time by supporting neurotransmitters involved in cell communication, but they do not treat the underlying disease or delay its progression.

A number of avenues are now being investigated to intervene much earlier, says Dr. Lawrence Honig, director of the Clinical Core of the Alzheimer's Disease Research Center at Columbia University. Rather than focus on amyloid, Dr. Frank Longo, a professor of neurology and neurological sciences at Stanford University, is working on a way to keep brain cells from degenerating. He's testing a molecule called LM11A-31 that binds to receptors on the cells and triggers the receptors "in a way that counteracts that degenerative signaling inside the cell," he says. The drug is moving to phase two trials now.

Another clinical trial just getting underway, organized by researchers at Brigham and Women's Hospital in Boston, will focus on an anti-amyloid antibody called solanezumab. The trial will rely on advanced brain scan technology to spot early amyloid buildup in people who have no signs of Alzheimer's and will test whether the drug could have an effect at this stage.

"We hope that starting treatment much earlier in the disease, before symptoms are present, as well as treating for a longer period of time, will slow cognitive decline and ultimately prevent Alzheimer's disease dementia," says Dr. Dennis Selkoe, a Harvard Medical School neurologist and co-director of Brigham's new Ann Romney Center for Neurological Diseases. A thousand participants across more than 60 sites in the U.S., Canada and Australia will be monitored for three to five years to determine whether solanezumab can help the brain to clear the amyloid beta and delay or prevent the onset of symptoms.

The Ann Romney Center was designed to accelerate treatments for and prevention of all the major brain diseases by gathering researchers focused on the different disorders in one place to share their work. It grew out of a conversation that Ann Romney, the wife of former Massachusetts Gov. Mitt Romney, had with Dr. Howard Weiner, director of the Multiple Sclerosis Program at Brigham and Women's. Romney has MS, and Weiner, who is her neurologist, mentioned how MS research was leading to breakthroughs in Alzheimer's disease; protollin, a drug he had studied for MS, for example, unexpectedly cleared plaques from the brains of mice. Fascinated by that potential for collaboration to speed results, Romney spearheaded a fundraising effort. The center will house up to 300 researchers as well as serve patients with a range of brain disorders.

Weiner and Selkoe have been collaborating to develop vaccines for MS and Alzheimer's. In the case of Alzheimer's, Weiner says, they are now working with several pharmaceutical companies to manufacture a protollin-based nasal vaccine that could be tested as a way to clear plaque in people. Like the solanezumab trial, the nasal vaccine is aimed at slowing the disease or even preventing it.

[See: Easy Ways to Protect Your Aging Brain.]

With Peter Rathmell