Neurologist Lee Stein Has High Hopes for Promising New Drug
As a student in the late 1970s at the Medical College of Georgia, Lee Stein, MD, became interested in neurology because he likened the work to solving a puzzle.
This was before MRIs came along and treatments were scarce to non-existent for neurologic diseases and disorders such as multiple sclerosis, Parkinson's and epilepsy. Doctors had to evaluate patients based on history and examination.
But over the course of Stein's career, including 15 years at Semmes Murphey and now 17 years at Neurology Clinic in Cordova, medications have become available to treat those illnesses.
"The disease that's out there that we really haven't answered the question of how to stop it, how to slow it down with medications where we can alter the course of the disease, is Alzheimer's," he said.
So now, as he did in his early days as a neurologist, Stein is back to trying to solve a puzzle. He and his group are involved in several studies, including an ENGAGE global trial of the pre-Alzheimer's drug aducanumab, a Biogen product. This drug, like a number of others, is a monoclonal antibody that targets amyloid, which causes damage to the brain.
"Approximately two years ago, positive Phase 1 aducanumab trial results were made available," Stein said. "There was a palpable excitement in neurology, Alzheimer's and business circles. I reviewed this data with my research coordinator, and within three months we were involved in the trial.
The doctor said Neurology Clinic became more involved with research six or seven years ago, including MS-related research.
"I have a big interest in multiple sclerosis and have a large MS practice," he said. "We were involved with four medications that ended up going out onto the market. So as we worked through this, Alzheimer's was sort of the next step.
"It became very obvious that the next interest that I had or the group had was to get actively into Alzheimer's research."
Although dementia has been around since ancient times, it wasn't until 1901 that the disease became associated with German psychiatrist Alois Alzheimer. Yet it wasn't until much later in the century that Alzheimer's disease fully entered the public's conscience. Until then, problems with memory were generally labeled as senility or dementia.
That began to change as the population started to live longer. Now, according to the Alzheimer's Association, more than 5 million Americans have Alzheimer's, and that number could grow to 16 million by 2050.
"Unfortunately, as we grow older, Alzheimer's becomes more and more common," Stein said. "When our parents and our grandparents 30 years ago were living into their mid to late 70s, many of them didn't grow old enough to develop Alzheimer's disease.
"By age 80, close to 40 percent of 80-year-olds will have Alzheimer's. By age 85, 50 percent will have it."
Also worrisome is the cost related to the disease.
"If we get down to the nitty gritty, it's a disease that's going to cost probably close to $250 billion this year to support and care for these individuals," he said. "It's a huge problem - the cost of medicine and how we can afford this."
As Alzheimer's has become more prominent, research has increased accordingly. Within the past five to 10 years, Stein said, "we're seeing huge amounts of research, huge amounts of money going into research projects. A lot of this is coming from pharmaceutical companies, obviously.
"At present there are more than 100 agents out there in the pipeline, and about 70 percent of those are diseased-modifying agents, agents that are trying to slow down the progression of the disease. The other 30 percent are more symptomatic to try to improve cognitive function. We want to do both.
"We have several medications that can help cognitive function but really don't alter the course of the disease, meaning you come off that medication and you drop back to the level where you would be without the medicine."
Even more recently, neurologists have adopted a new approach - start treatment earlier.
"As we've gotten deeper into research," Stein said, "we've realized that we don't want to wait for patients to develop Alzheimer's. We want to find patients in a pre-Alzheimer's situation, patients who have mild cognitive impairment or even almost normal cognitive function. The idea is to catch patients early on and try to treat them, to try to slow or stop the progression of the disease altogether."
The fact that some prospective medications for Alzheimer's have proved ineffective has led researchers to conclude that maybe they didn't start the medications soon enough.
In the meantime, one of the difficulties for not only patients but also doctors is how to distinguish between memory lapses of normal aging vs. the onset of Alzheimer's. Stein's evaluations generally begin with taking a patient's history and some memory testing. That often is followed by an MRI, and possibly laboratory studies "which really rule out other etiologies. On occasion we will send patients for a more extensive neuropsychologic evaluation."
Also available are PET scans, which offer a way to asses risk of Alzheimer's by evaluating how glucose is metabolized in the brain. Amyloid scans, performed almost exclusively in research studies because of their cost, check for telltale amyloid deposits in the brain.
They are all pieces in what has proved to be a very challenging puzzle.