Biopsied brain tissue yields regenerative cells - potential Parkinson's therapy?

TORONTO – Canadian researchers are taking a novel approach in trying to find an effective treatment for Parkinson’s disease — and it involves taking advantage of small holes drilled in the skull for another therapeutic procedure.

During surgery to implant electrodes into the brains of Parkinson’s patients — an increasingly common procedure known as deep brain stimulation, or DBS — doctors at Western University have been removing a tiny scoop of brain cells from selected patients, then growing them in the lab.

The hope is that regenerative cells contained in the biopsied tissue could one day be reprogrammed as therapeutic agents and reimplanted into a patient’s own brain to treat Parkinson’s or other neurodegenerative diseases like Alzheimer’s and multiple sclerosis.

“With further advances, it’s possible that these cells could be transformed in the laboratory to yield specific cell types needed for a particular disease, for example, dopamine neurons in Parkinson’s disease,” said neurosurgeon Dr. Matthew Hebb.

In Parkinson’s disease, brain cells that secrete the chemical dopamine are progressively destroyed, leading to tremors and other movement-related symptoms.

In a recently published study of 19 Parkinson’s patients who had brain biopsies during DBS surgery, the researchers say they were able to grow millions of patient-specific cells, which would not be rejected by the body’s immune system if reimplanted.

While most of the cells eventually stop dividing and die, “what takes over is this population of cells that has a very good regenerative capacity,” Hebb, who led the study, said Wednesday from London, Ont.

“It looks like they’re a type of progenitor cell, but they have a very complex makeup,” he said. “We’ve grown these cells and they have characteristics of cells that may be potentially manipulated into a particular cell type.”

Progenitor cells are early descendants of stem cells. Like stem cells, they can give rise to different types of cells, but unlike their ancestors, they cannot divide and reproduce indefinitely.

The cells grown by Hebb’s team express proteins, called neurotrophic factors, that protect brain cells. So it’s possible they might somehow be recruited to halt the progression of Parkinson’s disease by stopping the death of neurons in affected parts of the brain.

The key question to answer, he said, is what is the potential of these cells?

“And I think it’s important, especially when we talk about Parkinson’s disease and other neurodegenerative conditions, it’s important that we don’t characterize these cells as growing neurons from patients’ brains because we don’t have evidence that that’s what we’ve done.”

The research team, whose study is the cover story in the October issue of the Federation of American Societies for Experimental Biology journal, has begun studies to test how the human cells function when implanted into the brains of specially bred lab animals.

But Hebb said it likely will be many years of testing before researchers know if the implanted cells would be safe for humans and effective as a treatment.

Scientists, he said, need to look for better ways to get therapeutic agents into patients’ brains. Many drugs or potential cell-based therapies given orally or by IV injection are unable to successfully breach the blood-brain barrier, so they can’t directly target diseased areas of the brain.

“We really need to think outside the box and look at innovative strategies to approach these problems,” said Hebb. “And I think this is a new way to look at cell therapy.”

Dr. Andres Lozano, head of neurosurgery at the University of Toronto, treats patients with Parkinson’s and other conditions using deep brain stimulation. He called the London group’s research “a pretty exciting finding.”

“It has implications because we might be able to, for example, use these cells and expand them and put them back into the brain or we might be able to use these cells to test new drugs to see if they’re effective,” Lozano, who was not involved in the research, said from Montreal.

Lozano was in Montreal attending the World Parkinson Congress, a four-day meeting that has brought together about 3,000 people from around the world — patients with the disease, clinicians who treat them and researchers working toward treatments and a cure.

One of the most thought-provoking presentations came from researchers at the University of Pennsylvania, who are looking at how Parkinson’s disease spreads in the brain, a process that is not understood, he said.

The group led by Dr. Virginia Lee hypothesizes that the progression may result from abnormal molecules subverting normal molecules one by one to “propagate illness through the brain,” he said.

“It starts off probably in a small area and can spread like a fire that spreads in the forest … It’s a new avenue, a new idea, the fact that Parkinson’s can spread almost like an infection in the brain.”

Lozano said such research suggests that doctors need to start identifying Parkinson’s and treating it long before symptoms appear because the initial spark for the disease is obviously lit years earlier.

For patients with a family history of the disease, imaging studies might be able to show if the disease in its early stages is lurking in the brain, he said.

“That would be the time to intervene.”

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