Stem Cell For Parkinsons Disease? Prof. Jun Takahashi Study – Kyoto University

Stem cells can treat Parkinson’s symptoms in monkeys — Japanese scientists. Dopamine makes us human. A neurotransmitter in the brain, it regulates movement and emotional response, and plays a major role in feeling pleasure and learning.

Low levels of dopamine cause depression, loss of motor control, addictions, cravings, compulsions and poor attention and focus. Schizophrenia, attention deficit disorders and other psychiatric disorders are also linked to dopamine activity gone awry.

Lack of this neurotransmitter also causes Parkinson’s disease — the dreaded neurodegenerative disorder that gained wider public understanding after American actor and 1980s teen heartthrob Michael J. Fox revealed in 1998 that he suffered from it.

Death of brain cells in the substantia nigra, a structure in the brain’s mid region in charge of reward, addiction and movement, is what causes the dopamine shortage in Parkinson’s.

While Parkinson’s doesn’t involve a lot of physical pain, it’s still a terrible disease. First, it involves a lot of mental pain. Half of all people who suffer from Parkinson’s also endure clinical depression, anxiety and panic attacks — sudden, overpowering fears that come like storms together with breathlessness, sweating, chest pain, choking and dizziness.

Beginning with problems in walking or talking, the disease is marked by trembling arms and legs, muscular rigidity and poor balance. Parkinson’s sufferers have difficulty sleeping at night, and then consequently, feel drowsy during the daytime.

The disease worsens over time, and a third of sufferers go on to develop dementia — failing memory, short attention span and personality changes. The remaining who don’t, still suffer from a slowing down of information processing that makes it hard to complete simple mental tasks.

Drugs can be used to alleviate the most troubling symptoms of Parkinson’s, but today, there’s still no cure.

Right now, nothing can stop the disease’s awful advance — even it’s the second most common neurodegenerative disorder after Alzheimer’s disease. More than six million people worldwide — about 1.7 million in China, one million in the United States, about 100,000 in Canada and 1.2 million Europeans — suffer from Parkinson’s.

No cure yet exists, but scientists across the world are hard at work searching for one.

Stem cell for Parkinsons Disease?
Recently Japanese researchers used human embryonic stem cells (hESCs) to create dopamine-producing nerve cells, which they transplanted into four crab-eating monkeys that had Parkinson’s disease — successfully reducing the symptoms in the lab animals.

This breakthrough is particularly significant because it means the world is much closer to finding a cure for Parkinson’s.

In general, very early studies of stem cell therapies for various diseases are tested first in the lab on the different types of cells that are normally affected by one disease or another. It’s only when these treatments are shown to be successful several times over that they’re tested on animals.

First, they’re tested repeatedly on small animals — mainly lab rats or mice. After such tests on small-animals have been consistently successful, then the treatments can be tested on larger animals –goats and such.

It’s only after successful tests on large animals that treatments are tested on primates, which are genetically closer to human beings. When a therapy is repeatedly found to be successful in treating primates, then clinical trials on human beings are allowed — first to check that the treatment is safe and does not pose any harm to people, then to test if these treatments are effective.

The Japanese researchers led by Associate Prof. Jun Takahashi of the Kyoto University’s Institute for Frontier Medical Sciences are the first scientists in the world to report success of a stem cell treatment in primates. The study was reported in the online edition of U.S. journal Stem Cells.

Embryonic stem cells or hESCs, harvested from inside a blastocyst that develops from a human egg cell about a week after it’s fertilized, are pluripotent — that means they have the potential to become almost any type of tissue in the body.

What Dr. Takahashi and his team did was to use hESCs to cultivate a cell mass that was 35 percent composed of dopamine-producing neurons. They then transplanted these neurons into the four monkey and observed the lab monkeys over a one-year period.

Before the transplantation, all monkeys had violent shaking in their limbs — a classic symptom of Parkinson’s disease — and were unable to control their bodies. According to the researchers, the primates had remained nearly motionless inside their cages all day long before the transplant.

But three months after receiving the dopamine-producing nerve cells, they began to show improvements in their motor control, Dr. Takahashi told the Agence France Presse. About six months after the transplant, the primates were able to walk around their cages, he says.

The research team confirmed that normal nerve cells had been created in their brains after the transplant.

Raise neuron survival rate, lessen tumors
At the time of the implant, about 35 percent of the stem cells had already grown into dopamine neuron cells and a year after, around 10 percent remained alive.

Dr. Takahashi says he wants to increase the survival rate of dopamine neuron cells to 70 percent — thus improving the treatment’s effectiveness.

While the Japanese team has so far used embryonic stem cells — something that’s deemed unconscionable by religious persons — it’s likely to switch in the future to using induced pluripotent stem cells (iPSCs) that are created from human skin. That’s both to skirt the controversy over using human embryos, as well as to lessen the chance that donor stem cells are rejected by recipients after being transplanted — which is what happens when donors and recipients don’t match genetically.

Because of early controversy surrounding the use of hESCs, in 2006, scientists developed an alternative technique called induced pluripotency. This involved adding “transcription factors” to specialized cells like those found in skin to drive them back along the developmental timeline to an undifferentiated stem-cell-like state.

These iPSCs are then grown under various specific conditions to induce them to re-specialize into many different cell types. But the process often results in cancer-causing genes being activated; Pluripotent cells often cause cancers when transplanted into animals or humans.

In fact, the team’s just done that — transplanted iPSCs into monkeys — and are now looking to see if the monkeys with Parkinson’s disease show similar improvements in their motor control.

While the new findings hold promise for treating Parkinson’s using regenerative medicine, Japanese news agency Mainichi Shimbun reports that “more work is needed to find an effective treatment method as the study showed that derived nerve cells that were not appropriately matured led to the development of tumors.”

But the tumors were not malignant and could be treated, Mainichi reports.

“The challenge before applying it (the stem cell treatment) to a clinical study is to raise the number of dopamine neuron cells and to prevent the development of tumors,” Dr. Takahashi says.

“We’ll make further efforts to enhance the safety of these cell transplants,” Dr. Takahashi says. “And we hope to start clinical application studies as early as three years from now.”

iNPCs, iPSC technique without cancer risk, Parkinson’s cell replica
Earlier, American researchers from the Stanford University School of Medicine showed that skin from mice and humans could be directly converted into the “precursor” cells that become the three main parts of the nervous system — neurons, astrocytes and oligodendrocytes.

The newly created “induced neural precursor cells” or iNPCs are more flexibility and can be cultivated in large numbers in the lab. That’s important if they’re to be useful in transplantation or drug screening, the researchers explain. The findings were published online Jan. 30 in the Proceedings of the National Academy of Sciences.

Further down south in the U.S., a team of scientists at the University of Central Florida led by an American bioengineer of Japanese descent, Dr. Kiminobu Sugaya, developed a new iPSC technology.

The revolutionary technique allows scientists to generate millions of the type of stem cells they want from a single cell taken from an adult — without the usual risk of cancer.

The UCF technique uses only one gene to spur the creation of stem cells from an adult cell. The gene, called NANOG, has the genetic blueprint for a protein molecule known as a transcription factor. Dr. Sugaya’s team believes that this NANOG transcription factor is what helps stem cells maintain their pluripotency.

In New York, researchers at the University of Buffalo have recently applied a stem-cell engineering technique to successfully create Parkinson’s-in-a-dish — human brain cells that are an exact replica of neurons in one type of Parkinson’s disease.

By developing these brain cells in the lab, researchers can now study how brain cells function in Parkinson’s patients without having to conduct invasive brain surgery — something impossible given the limitations of today’s medical technologies.

With the newly developed cells, researchers are observing 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.

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