Brain cell replacement for Parkinson’s boosted by monkey study – The San Diego Union-Tribune

By JoanneRUSSELL25

A brain cell replacement therapy reduced Parkinsons disease symptoms in monkeys, Japanese researchers report in a study released Wednesday. The positive result boosts prospects to test the therapy in people.

The goal is to implant neurons derived from stem cells into the brains of Parkinsons patients, a project pursued by scientists in San Diego, New York, Britain and Sweden as well as in Japan. If all goes well, the neurons will function as replacements for those destroyed in the disease.

In addition, human testing of a related brain cell therapy from Carlsbads International Stem Cell Corp. is already under way in Australia.

While treatments exist for the movement disorders caused by Parkinsons, none of them actually halt progression. Replacing the brain cells destroyed in Parkinsons holds the promise of actually reversing the disease.

Moreover, success with Parkinsons could pave the way to treating many other neurodegenerative diseases, such as ALS (Lou Gehrigs disease) and perhaps Alzheimers, along with brain and spinal cord injuries. These afflictions cost hundreds of billions annually, and most importantly, produce immense suffering in patients and caregivers.

Years of extensive research are required before any such therapy can be tried in people. Testing in monkeys or other primates is often regarded as the last step before human treatment can be contemplated.

The study was published in the journal Nature. Its senior author was Jun Takahashi, a prominent stem cell researcher at Kyoto University in Kyoto, Japan. Go online to for the study.

There is precedent to suggest the therapy might work. Beginning decades ago, brain cells taken from human fetuses have been implanted into the brains of Parkinsons patients, with mixed results. Some patients experienced improved movement control. But others gained nothing, or experienced uncontrolled movements.

Scientists in the field say using stem cells should provide improved results. Stem cells can be made in greater quantity than the limited number of fetal brain cells available. In addition, the stem cells and neurons made from them can be analyzed for quality before implantation.

The study was praised by regenerative medicine researcher Tilo Kunath at the University of Edinburgh, in comments provided by the UK Science Media Centre.

This is extremely promising research demonstrating that a safe and highly effective cell therapy for Parkinsons can be produced in the lab, Kunath said.

Such a therapy has the potential to reverse the symptoms of Parkinsons in patients by restoring their dopamine-producing neurons. The next stage will be to test these therapies in a first-in-human clinical trial.

In the study, researchers produced neurons that secrete dopamine, a neurotransmitter deficient in Parkinsons disease. These neurons were made from human stem cells derived from both healthy people and those with Parkinsons.

The researchers then implanted the human neurons into 10 monkeys whose own dopamine-making neurons had been destroyed. The monkeys were given immunosuppressive drugs to prevent rejection of the human cells.

The human neurons integrated into the brains of the monkeys and functioned as dopamine-making neurons. The monkeys improved in movement ability, save for one monkey that became ill and was euthanized. Both cells from healthy and Parkinsons patients were effective.

A companion study in Nature Communications demonstrated a method of immune-matching the cells to reduce the immune response. Takahashi was also senior author of that study. Go online to for the study.

Both studies used artificial embryonic stem cells, called induced pluripotent stem cells (IPS). These act-alike cells are not derived from embryos, but are genetically reprogrammed from adult cells, usually skin cells.

The IPS cells appear to act virtually identically to embryonic stem cells, but dont raise the ethical objections many have to using embryonic stem cells. These cells were invented in 2006 by a team led by Shinya Yamanaka, a co-author of the Nature Communications study.

Moreover, the cells can be made from the patients themselves, which is not expected to cause an immune reaction. This is the approach taken by the San Diego team, including scientists at The Scripps Research Institute.

Carlsbads International Stem Cell Corp. uses a different approach. It starts with unfertilized, or parthenogenetic, human egg cells. These are grown into immature neurons that are implanted. The cells are expected to grow not only into dopamine-making neurons, but other kind of brain cells that preserve the remaining neurons.

The Australian clinical trial has gathered evidence of safety, and continued testing is under way determine efficacy.

The Nature study dovetails with research by the San Diego group, Summit for Stem Cell, (, including scientists at The Scripps Research Institute and doctors at Scripps Health.

The group proposes to treat Parkinsons patients with neurons grown from their own IPS cells. The scientists have received funding from the California Institute for Regenerative Medicine, the states stem cell agency.

The studies support the personalized approach that we are taking for a neuron replacement therapy for Parkinson's disease patients, said Jeanne Loring and Andres Bratt-Leal, stem cell scientists at The Scripps Research Institute.

Two points from the studies should be highlighted, Loring and Bratt-Leal said by email.

Parkinson's disease is a late-onset disorder, they said. That means that there was nothing wrong with the neurons that people with Parkinson's were born with. Few PD patients have a family history of the disease, which suggests that genetic mutations did not cause their disease.

So for the great majority of patients, transplantation of their own neurons is a promising approach to relieving symptoms, without having to take expensive and risky immunosuppressive drugs, they said.

The Summit for Stem Cell scientists are members of an international partnership of laboratories developing neuron replacement therapies for Parkinsons, called GForce PD.

Takahashi belongs to the partnership, as do scientists in the UK, Sweden and New York. These use both embryonic and IPS stem cells. The Summit for Stem Cell effort is the only one using patient-matched IPS cells, Loring and Bratt-Leal said.

Brain cells reprogrammed to make dopamine, with goal of Parkinsons therapy

Parkinson's stem cell therapy shows signs of safety

Parkinson's therapy funded by California's stem cell agency

Dopamine-making neurons can be chemically controlled in animal model of Parkinson's

Stem cell clinical trial for Parkinson's begins

Summit for Stem Cell

(619) 293-1020

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