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“Artificial” Stem Cells May Help Reveal Parkinson’s Causes, Treatments

In a study published in the July 4, 2012 issue of Science Translational Medicine, researchers report that they have generated “artificial” stem cells from five people living with inherited forms of Parkinson’s. Induced pluripotent stem cells (iPSCs) are artificial stem cells that scientists make in the lab by taking cells from adults (often from the skin) and treating them to remove their “specialized” function. After developing iPSCs, researchers can manipulate the cells into more specialized types.

A multi-institutional research team that included PDF-supported scientists generated the iPSCs in this study from people with mutations in PINK1 or LRRK2, two genes linked to inherited PD. The team was led by Ole Isacson, M.D., at Harvard Medical School and funded by the National Institute of Neurological Disorders and Stroke. After creating the iPSCs, Dr. Isacson’s team grew them into dopamine neurons, the cell type affected by PD. They compared them with similarly iPSC-derived neurons created from two people without PD.

Results

  • iPSC-derived neurons from people with genetic forms of PD were more vulnerable to toxic chemicals than were neurons from healthy people.
  • Neurons from people with genetic forms of PD showed impaired mitochondrial functioning and energy production as compared with neurons from healthy people.
  • Researchers “rescued” PD neurons from mitochondrial problems by treating them with chemicals such as coenzyme Q10. The different genetic forms of PD showed different responses to the treatments.

What Does It Mean?

In spite of progress, scientists do not know what causes PD, even among the minority of people with PD who carry known genetic mutations. By studying iPSCs,

Dr. Isacson and his colleagues tried to better understand the cellular mechanism for PD. They theorize that the cells from people with genetic forms of PD were more sensitive to chemical exposure because of problems in mitochondria, which cause a shortage of energy in the cell. Their use of iPSC technology is of interest because skin cells can be easily obtained and could be used one day to tailor therapies uniquely suited to an individual. In fact, this study suggests that different forms of PD may respond differently to treatments.

Researchers need to next generate iPSCs from a larger group of people, including those with sporadic PD, to confirm these results.

 

Colonoscopy May Detect Early Parkinson’s Disease

In the future, doctors may be able to diagnose early Parkinson’s disease (PD) with a colonoscopy, according to a new study funded in part by the Parkinson’s Disease Foundation (PDF) and published in the May issue of Movement Disorders. In PD, a protein called alpha-synuclein forms abnormal clumps, killing the brain’s dopamine-producing neurons. Scientists have also detected alpha-synuclein clumps in nerve cells of the colon and skin of people with PD. This had led to a theory that PD begins in tissues outside the brain. Kathleen Shannon, M.D., and her colleagues at the PDF Research Center at Rush University Medical Center wondered whether the presence of alpha-synuclein aggregating in colon tissue could predict PD development. They studied colon biopsy samples from three people with PD, collected by colonoscopy two to five years before the people showed symptoms of PD. They detected alpha- synuclein by staining the protein with dyes or fluorescent molecules.

Results

  • Alpha-synuclein protein was detected in nerve cells of colon tissue from all three people who later developed symptoms of PD.
    No alpha-synuclein was detected in colon tissue samples from 23 healthy people without PD.

What Does It Mean?

The detection by Dr. Shannon’s team of alpha-synuclein in the colon tissue samples of people who later developed PD, supports a hypothesis that the disease may possibly begin in neurons of the intestinal wall and later spread to the brain. This study is the first to show alphasynuclein in colon tissue before onset of PD. Doctors diagnose PD by observing symptoms such as tremor. Yet up to 20 percent of suspected cases of PD are misdiagnosed.

If the findings from this very small study are replicated in studies involving larger samples, it may be possible one day to use colonoscopy to predict who will develop PD. Because doctors already recommend that people age 50 and older have a colonoscopy every few years, it would be relatively easy to test colon tissue biopsies for the alpha-synuclein protein.

Early detection of PD would help facilitate a search for a cure, or for interventions that slow the disease. But first, it will be important to confirm the results in larger populations of people with and without PD.

 

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Next in Fall 2012 News & Review: How the Brain Copes with Parkinson's