Stem Cell-Derived Dopaminergic Neurons Rescue Motor Defects in Parkinsonian Monkeys

Source: Journal of Clinical Investigation

Date December 3, 2012

 Researchers have derived dopaminergic neurons from bone marrow stem cells in monkeys.

Parkinson's disease is a degenerative disorder of the central nervous system that is characterized by tremors, rigidity, slowness of movement, and difficulty walking. It is caused by loss of the neurons that produce the neurotransmitter dopamine (known as dopaminergic neurons). One of the primary goals in Parkinson's disease research is to develop a replacement for dopaminergic neurons.

In a new study, researchers led by Takuya Hayashi at the RIKEN Center for Molecular Imaging Science in Kobe, Japan, derived dopaminergic neurons from bone marrow stem cells in monkeys. The cells were retrieved during a standard bone marrow aspiration and then treated with growth factors that directed the stem cells to become dopaminergic neurons. The monkeys that donated the stem cells were treated with a chemical to induce Parkinson's disease and then received a transplant of the new dopaminergic neurons that had been derived from their own bone marrow stem cells. Monkeys that received the transplant showed significant improvement in motor defects.

This study demonstrates that dopaminergic neurons derived from adult bone marrow stem cells can be safely used to improve motor function in Parkinson's disease in monkeys.

The research is published in the Journal of Clinical Investigation.

Scientists Pinpoint Key Player in Parkinson's disease neuron loss Stem cell study may help to unravel how a genetic mutation leads to Parkinson's Symptoms

Source: Salk Institute for Biological Studies
Date: October 19, 2012

LA JOLLA, CA—By reprogramming skin cells from Parkinson's disease patients with a known genetic mutation, researchers at the Salk Institute for Biological Studies have identified damage to neural stem cells as a powerful player in the disease. The findings, reported online October 17, 2012 in Nature, may lead to new ways to diagnose and treat the disease.

The scientists found that a common mutation to a gene that produce the enzyme LRRK2, which is responsible for both familial and sporadic cases of Parkinson's disease, deforms the membrane surrounding the nucleus of a neural stem cell. Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons, such as the ones that respond to dopamine.

The Salk researchers found that a common genetic mutation involved in Parkinson's disease deforms the membranes (green) surrounding the nuclei (blue) of neural stem cells. The discovery may lead to new ways to diagnose and treat the disease.

Researchers Turn Skin Cells into Brain Cells, A Promising Path To Better Parkinson's Treatment

Source: Johns Hopkins Medicine
Date: July 17, 2012

Summary:

Using adult stem cells, Johns Hopkins researchers and a consortium of colleagues nationwide say they have generated the type of human neuron specifically damaged by Parkinson’s disease (PD) and used various drugs to stop the damage. Their experiments on cells in the laboratory, reported in the July 4 issue of the journal Science Translational Medicine, could speed the search for new drugs to treat the incurable neurodegenerative disease, but also, they say, may lead them back to better ways of using medications that previously failed in clinical trials.

Patient-derived Stem Cells Could Improve Drug Research for Parkinson's

Source: National Institute of Neurological Disorders and Stroke
Date: July 4, 2012

Summary:

Researchers have taken a step toward personalized medicine for Parkinson's disease, by investigating signs of the disease in patient-derived cells and testing how the cells respond to drug treatments. The study was funded by the National Institutes of Health.

The researchers collected skin cells from patients with genetically inherited forms of Parkinson’s and reprogrammed those cells into neurons. They found that neurons derived from individuals with distinct types of Parkinson's showed common signs of distress and vulnerability – in particular, abnormalities in the cellular energy factories known as mitochondria. At the same time, the cells' responses to different treatments depended on the type of Parkinson's each patient had.

The results were published in Science Translational Medicine.

Rebuilding the brain’s circuitry Healthy neurons can integrate into diseased areas

Source: Harvard Medical School
Date: November 24, 2011

Summary:

Neuron transplants have repaired brain circuitry and substantially normalized function in mice with a brain disorder, an advance indicating that key areas of the mammalian brain are more reparable than was widely believed. Collaborators from Harvard University, Massachusetts General Hospital (MGH), Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) transplanted normally functioning embryonic neurons at a carefully selected stage of their development into the hypothalamus of mice unable to respond to leptin, a hormone that regulates metabolism and controls body weight. These mutant mice usually become morbidly obese, but the neuron transplants repaired defective brain circuits, enabling them to respond to leptin and thus experience substantially less weight gain.

Repair at the cellular-level of the hypothalamus — a critical and complex region of the brain that regulates phenomena such as hunger, metabolism, body temperature, and basic behaviors such as sex and aggression — indicates the possibility of new therapeutic approaches to even higher-level conditions such as spinal cord injury, autism, epilepsy, ALS (Lou Gehrig’s disease), Parkinson’s disease, and Huntington’s disease.


The findings are to appear Nov. 25 in Science.

Stem Cell Study Offers Hope for Parkinson's Patients

Source: University of Edinburgh
Date: August 23, 2011

Summary:

Scientists at the University of Edinburgh have for the first time generated stem cells from one of the most rapidly progressing forms of Parkinson's disease. The development will help research into the condition as it will enable scientists to model the disease in the laboratory to shed light on why certain nerve cells die.

The research, led by the University of Edinburgh in collaboration with UCL (University College London), then used these skin cells to generate brain nerve cells affected by the disease. The ability to generate these nerve cells will make it easier to monitor the effectiveness of potential new drugs that could slow or halt progress of the condition. The aim would be to find drugs that can prevent the death of these key cells -- known as neurons -- which break down as a result of Parkinson's. The research was published in the journal Nature Communications.

Hope for millions of Alzheimer's sufferers as scientists make brain cells from human skin

Source: The Independent
Date: 14 July 2011


The Independent reports researchers from the Stanford University School of Medicine have converted adult skin cells directly into mature nerve cells:

Skin cells from a 30-year-old woman have been turned directly into mature nerve cells similar to those found in the brain using a procedure that promises to revolutionise the emerging field of regenerative medicine. Scientists said they were astonished to discover that they could convert a person's skin tissue into functioning nerve cells – bypassing an intermediate stem-cell stage – by the relatively simple procedure of adding a few short strands of RNA, a genetic molecule similar to DNA. The breakthrough could soon lead to the generation of different types of human brain cells in a test tube which could be used to study a range of neurodegenerative conditions such as Parkinson's and Alzheimer's disease.

Efficient process using microRNA converts human skin cells into neurons, study shows

Source: Stanford University
Date: July 13, 2011

Summary:

The addition of two particular gene snippets to a skin cell’s usual genetic material is enough to turn that cell into a fully functional neuron, report researchers from the Stanford University School of Medicine. The finding, published online July 13 in Nature, is one of just a few recent reports of ways to create human neurons in a lab dish. The new capability to essentially grow neurons from scratch is a big step for neuroscience research, which has been stymied by the lack of human neurons for study.

Stem Cells Reverse Disease in a Model of Parkinson's Disease

Source: Journal of Clinical Investigation
Date: May 16, 2011

Summary:

A team of researchers -- led by Sang-Hun Lee, at Hanyang University, Republic of Korea, and Kwang-Soo Kim, at Harvard Medical School, Belmont, -- has now compared the ability of cells derived from different types of human stem cell to reverse disease in a rat model of Parkinson disease and identified a stem cell population that they believe could be clinically relevant.

The researchers found several problems with cells derived from virus-based human iPS cells that precluded their use in the Parkinson disease model but found that nerve cells derived from protein-based human iPS cells reversed disease when transplanted into the brain of rats modeling Parkinson disease. They therefore conclude that protein-based human iPS cells could be used in the treatment of individuals with Parkinson disease.

The study is published in the Journal of Clinical Investigation.

Dopamine Controls Formation of New Brain Cells

Source: Karolinska Institutet
Date: 8 April 2011

Summary:

A study of the salamander brain has led researchers at Karolinska Institutet to discover a hitherto unknown function of the neurotransmitter dopamine. In an article published in the scientific journal Cell Stem Cell they show how in acting as a kind of switch for stem cells, dopamine controls the formation of new neurons in the adult brain. Their findings may one day contribute to new treatments for neurodegenerative diseases, such as Parkinson's.

The study was conducted using salamanders which unlike mammals recover fully from a Parkinson's-like condition within a four-week period. Parkinson's disease is a neurodegenerative disease characterised by the death of dopamine-producing cells in the mid-brain. As the salamander re-builds all lost dopamine-producing neurons, the researchers examined how the salamander brain detects the absence of these cells. This question is a fundamental one since it has not been known what causes the new formation of nerve cells and why the process ceases when the correct number have been made.

What they found out was that the salamander's stem cells are automatically activated when the dopamine concentration drops as a result of the death of dopamine-producing neurons, meaning that the neurotransmitter acts as a constant handbrake on stem cell activity.

Stanford scientists build Parkinson's disease in a dish with cells from Google founder's mom

Source: San Jose Mercury News
Posted: March 27, 2011 07:56:46 AM PDT

Summary:

The San Jose Mercury News reports scientists at the Stanford University School of Medicine have grown cells with traits of Parkinson's disease in a lab:

...Stanford University scientists say they have re-enacted this tragedy in a petri dish -- growing the young neurons from the donated skin cells of Parkinson's patient Genia Brin, the mother of Google co-founder Sergey Brin -- and then watching them sicken and perish. This feat, co-authored in this month's issue of the journal Cell by Stanford's Renee Reijo Pera, could accelerate the search for a cure of the crippling disorder. The research makes it possible, for the first time in medical history, to study the diseased cells and test compounds that might slow or even prevent their development.

Research May Lead to New Treatments for Parkinson’s Disease and Other Neurological Disorders

Source: Marshall University Research Corporation
Date: March 24, 2011

Summary:

Scientists at Marshall University are conducting research that may someday lead to new treatments for repair of the central nervous system. The group has identified and analyzed unique adult animal stem cells that can turn into neurons. The neurons they found appear to have many of the qualities desired for cells being used in development of therapies for slowly progressing, degenerative conditions like Parkinson's disease and Huntington's disease and multiple sclerosis, and for damage due to stroke or spinal cord injury. The research was published in a recent issue of the Journal of Cellular Physiology.

Researchers discover drug that stops progression of Parkinson's disease in mice

Source: University of Colorado Denver
Date: March 8, 2011

Summary:

AURORA, Colo. – In a major breakthrough in the battle against Parkinson’s disease, researchers at the University of Colorado School of Medicine have discovered a drug that stops the progression of the degenerative illness in mice and is now being tested on humans. The results have been published on-line in the Journal of Biological Chemistry.

Scientists create neurons with symptoms of Parkinson's disease from patient's skin cells

Source: Stanford University School of Medicine
Date: March 3, 2011

Summary:

Neurons have been derived from the skin of a woman with a genetic form of Parkinson’s disease and have been shown to replicate some key features of the condition in a dish, say researchers at the Stanford University School of Medicine. The scientists hope to use the neurons to learn more about the disorder and to test possible treatments. Such a tool is critical because there are no good animal models for Parkinson’s disease. It also validates the use of induced pluripotent stem cells, or iPS cells, to model various diseases. The research which appears in the March issue of Cell Stem Cell.

Scientists successfully use human induced pluripotent stem cells to treat Parkinson's in rodents

Source: Buck Institute for Age Research
Date: August 16, 2010

Summary:

Researchers at the Buck Institute for Age Research have successfully used human induced pluripotent stem cells (iPSCs) to treat rodents afflicted with Parkinson's Disease (PD). The research, which validates a scalable protocol that the same group had previously developed, can be used to manufacture the type of neurons needed to treat the disease and paves the way for the use of iPSC's in various biomedical applications. Results of the research, from the laboratory of Buck faculty Xianmin Zeng, Ph.D., are published August 16, 2010 in the on-line edition of the journal Stem Cells.

A news story was published about this study in today's Contra Costa Times.

Stem cells to aid study of Parkinson's

Source: University of Oxford
Date: 15 July 2010

Summary:

A new stem cell technology is to be used by Oxford University researchers to better understand the causes of Parkinson’s disease. The technique will use skin samples to grow the brain cells thought to be responsible for the onset of Parkinson’s disease, allowing these important neurons to be studied in detail.

Researchers will gather data from over 1,000 patients with early stage Parkinson’s disease and take small samples of skin tissue to grow special stem cells – induced pluripotent stem cells (iPS cells). iPS cells can be generated from accessible tissue such as the skin and then used to generate specific types of cell. The researchers will use the iPS cells to grow dopamine neurons, the brain cells responsible for the production of dopamine. It is these cells which die in patients with Parkinson’s, leading to the onset of the disease.

Endometrial Stem Cells Restore Brain Dopamine Levels. Mouse Study May Lead to New Therapies for Parkinson’s Disease

Source: National Institute of Child Health and Human Development (NICHD)
Date: May 6, 2010

Summary:

Endometrial stem cells injected into the brains of mice with a laboratory-induced form of Parkinson’s disease appeared to take over the functioning of brain cells eradicated by the disease. The finding raises the possibility that women with Parkinson’s disease could serve as their own stem cell donors. Similarly, because endometrial stem cells are readily available and easy to collect, banks of endometrial stem cells could be stored for men and women with Parkinson’s disease.

This is the first time that researchers have successfully transplanted stem cells derived from the endometrium, or the lining of the uterus, into another kind of tissue (the brain) and shown that these cells can develop into cells with the properties of that tissue. The findings appear online in the Journal of Cellular and Molecular Medicine.

Novel Parkinson’s treatment strategy involves cell transplantation

Source: University of California, San Francisco
Date: March 25, 2010

Summary:

Scientists at the University of California, San Francisco have used a novel cell-based strategy to treat motor symptoms in rats with a disease designed to mimic Parkinson's disease. The strategy suggests a promising approach, the scientists say, for treating symptoms of Parkinson's disease and other neurodegenerative diseases and disorders, including epilepsy.

The scientists transplanted embryonic neurons from fetal rats into an area of the adult rat brain known as the striatum, which integrates excitatory and inhibitory neurotransmitter signals to control movement. In Parkinson's disease, cells that produce the neurotransmitter dopamine are damaged, and thus unable to project their communication wires, or axons, to the region. As a result, the balance of excitation and inhibition in the striatum is lost, causing the motor deficits that are a primary symptom of the disease.

In the study, the transplanted embryonic neurons migrated and integrated into the correct neural circuitry of the striatum, matured into so-called GABAergic inhibitory interneurons, and dampened the over-excitation in the region. The rats had improved motor function, as seen in their balance, speed, and length of stride during walking. Moreover, the healthy "control" rats in which the cells had been transplanted took longer strides and ran faster on a runway test.

How the pathology of Parkinson's disease spreads

Source: University of California - San Diego
Date: July 27, 2009

Summary:

Accumulation of the synaptic protein α-synuclein, resulting in the formation of aggregates called Lewy bodies in the brain, is a hallmark of Parkinson’s and other related neurodegenerative diseases. This pathology appears to spread throughout the brain as the disease progresses. Now, researchers at the University of California, San Diego School of Medicine and Konkuk University in Seoul, South Korea, have described how this mechanism works. Their findings – the first to show neuron-to-neuron transmission of α-synuclein – will appear in the Proceedings of the National Academy of Sciences (PNAS) on July 29. This insight will impact research into stem cell therapy for Parkinson's disease

Researchers define ideal time for stem cell collection for Parkinson's disease therapy

Source: Thomas Jefferson University
Date: November 19, 2008

Summary:

Researchers have identified a stage during dopamine neuron differentiation that may be an ideal time to collect human embryonic stem cells for transplantation to treat Parkinson's disease, according to data presented at Neuroscience 2008, the 38th annual meeting of the Society for Neuroscience. Lorraine Iacovitti, Ph.D., professor and interim director of the Farber Institute for Neurosciences of Thomas Jefferson University, and her research team found that neural progenitor cells that express the gene Lmx1a are committed to the midbrain dopamine neuron lineage, but still retain proliferative capacity. Because of these characteristics, the stage at which Lmx1a is expressed may be ideal for transplantation.