Stem Cell Therapy for Parkinson’s Disease? U.S Study Offers Hope

Brain cells engineered in a lab sheds light on Parkinson’s disease, may bring cure. There isn’t much physical pain involved, but it’s still a terrible disease. Marked by trembling arms and legs, muscular rigidity and poor balance, Parkinson’s disease worsens over time.

Beginning with problems in walking or talking, one third of sufferers later go on to develop dementia — failing memory, short attention span and personality changes. Those who don’t still suffer from a slowing down of information processing that makes it difficult to complete simple tasks like balancing a checkbook.

Worse, almost half of Parkinson’s patients suffer from mental pain. They become clinically depressed and most suffer from anxiety and panic attacks—sudden, overpowering fears, accompanied by breathlessness, sweating, chest pain, choking and dizziness. Almost all Parkinson’s patients have to put up with an inability to sleep at night, then drowsiness during daytime.

For a long time, there’s been no cure for this terrible disease. Drugs can be used to alleviate some of the most troubling symptoms, but the disease’s terrible advance can’t be stopped.

But new research from New York’s University of Buffalo may soon usher the development of a cure.

In a breakthrough research they portray as a “game changer,” scientists in the United States have successfully applied a stem-cell engineering technique to create human brain cells that are an exact replica of neurons in one type of Parkinson’s disease.

At this stage of medical research, it’s still virtually impossible to study how brain cells function in Parkinson’s patients. By developing these brain cells in the lab, researchers from New York’s University of Buffalo have sidestepped having to conduct invasive brain surgery to study the brain disease.

The newly developed brain cells have allowed researchers to observe exactly how mutations in the parkin gene cause one type of the disease that affects one in 10 Parkinson’s patients.

In the other nine out of 10 Parkinson’s cases, scientists don’t understand why neurons die. But in 10 percent of cases, the disease is caused by a mutation of genes.

Studying the brain cells they created, the Buffalo University researchers were able to see how mutations of the parkin gene interrupt dopamine behavior, produce more free radicals—and by doing so destroy dopamine neurons, causing Parkinson’s disease.

The new research is a breakthrough in two ways:
• It has helped scientists get to the bottom of how Parkinson’s assails the human nervous system.
• It offers a realistic replica on which to test new treatments for Parkinson’s. This could help lead to the development of a drug to cure the genetic form of Parkinson’s, and maybe the other forms as well.

Before the researchers created the human neuron model, research on a cure for Parkinson’s faced this obstacle: researchers couldn’t study Parkinson’s in lab animals since the animals that lack the parkin gene don’t develop the brain disease.

“This is the first time that human dopamine neurons have ever been generated from Parkinson’s disease patients with parkin mutations,” says lead researcher Dr. Jian Feng.

“Before this, we didn’t even think about being able to study the disease in human neurons,” he adds. “The brain is so fully integrated. It’s impossible to obtain live human neurons to study.”

The study, published on Feb. 8 in the journal Nature, looks only at a tenth of Parkinson’s cases. But understanding how the parkin gene works can help shed light on the disease as a whole—as well as other brain-based diseases.

By enabling researchers to “non-invasively” study the disease at its cellular level, Dr. Feng says, his team’s accomplishment is advancing the study of Parkinson’s and other neurological diseases, “It finally allowed us to obtain the material we needed to study the disease.”

Stem cells to create the neural model
To make the human neurons the scientists used a technique successfully tested by other researchers in the past.

They took skin cells from four volunteers—two healthy control subjects and two people with Parkinson’s disease caused by a parkin gene mutation. They then transformed these into a type of stem cells called “induced pluripotent stem cells”— iPS cells, or iPSCs—that can develop into almost any type of cells in the body.

Then, they turned the iPSCs into brain cells and found that the cells from the Parkinson’s patients turned into brain cells that contained a mutated form of the “parkin” gene.

Human cells were first turned into IPSCs in 2007 by researchers in Japan. These stem cells are similar to embryonic stem cells, but are less controversial because they’re created from the cells of human adults and don’t require the destruction of embryos.

Only last month, researchers from the University of California San Diego led by neuroscientist Dr. Larry Goldstein independently applied the same technique to come up with a similar neural model of another neurodegenerative disease, Alzheimer’s disease.

What the researchers saw with the neuron model
The “Parkinson’s-brain-cells-in-a dish” they created allowed Dr. Feng’s team to observe the parkin gene at work.

In normal brains, parkin controls the production of an enzyme called monamine oxidase or MAO that, in turn, checks the brain-signaling chemical dopamine.

When parkin is mutated, the regulation is lost, how dopamine behaves is no longer controlled by brain cells—and what Dr. Feng calls the “neural computation” needed for movement is hindered.

According to him, human’s large brains may require more dopamine to control bipedal or fully upright movement, unlike the quadrupedal movement—or movement on all four limbs—of most mammals.

The mutation also causes the brain cells to lose their ability to control the production of monoamine oxidase (MAO) that can be toxic and, appear to contribute to oxidative stress at high levels, killing off dopamine neurons.

Maintaining the protective function of parkin could be key to finding a cure for Parkinson’s disease—and Dr. Feng’s team now want to test new treatments that might prevent this damage from happening, thereby stopping this form of Parkinson’s.

The researchers, in fact, have already shown that they can reverse the defect by putting a normal parkin gene into diseased neurons.

Dr. Michelle Gardner, research development manager at Parkinson’s United Kingdom, tells BBC that the study is particularly exciting because it provides a new way to investigate this genetic form of Parkinson’s.

“Parkinson’s UK funded research has already shown that parkin plays a key role in how Parkinson’s develops in the brain nerve cells that die,” she says.

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