Researchers from South Korea,
Sweden, and the United States
have collaborated on a project to restore neuron function to parts of the brain
damaged by Huntington’s disease (HD) by successfully transplanting HD-induced
pluripotent stem cells into animal models.
Induced pluripotent stem cells (iPSCs) can be genetically
engineered from human somatic cells such as skin, and can be used to model
numerous human diseases. They may also serve as sources of transplantable cells
that can be used in novel cell therapies. In the latter case, the patient
provides a sample of his or her own skin to the laboratory.
In the current study, experimental animals with damage to a
deep brain structure called the striatum (an experimental model of HD)
exhibited significant behavioral recovery after receiving transplanted iPS
cells. The researchers hope that this approach eventually could be tested in
patients for the treatment of HD.
“The unique features of the iPSC approach means that the
transplanted cells will be genetically identical to the patient and therefore
no medications that dampen the immune system to prevent graft rejection will be
needed,” said Jihwan Song, D.Phil. Associate Professor and Director of
Laboratory of Developmental & Stem Cell Biology at CHA Stem Cell Institute,
CHA University, Seoul, South Korea and co-author of the study.
The study, published online this week in Stem Cells, found
that transplanted iPSCs initially formed neurons producing GABA, the chief
inhibitory neurotransmitter in the mammalian central nervous system, which
plays a critical role in regulating neuronal excitability and acts at
inhibitory synapses in the brain. GABAergic neurons, located in the striatum,
are the cell type most susceptible to degeneration in HD.
Another key point in the study involves the new disease
models for HD presented by this method, allowing researchers to study the
underlying disease process in detail. Being able to control disease development
from such an early stage, using iPS cells, may provide important clues about
the very start of disease development in HD. An animal model that closely
imitates the real conditions of HD also opens up new and improved opportunities
for drug screening.
“Having created a model that mimics HD progression from the
initial stages of the disease provides us with a unique experimental platform
to study Huntington’s disease pathology” said Patrik Brundin, M.D., Ph.D.,
Director of the Center for Neurodegenerative Science at Van Andel Research
Institute (VARI), Head of the Neuronal Survival Unit at Lund University, Sweden,
and co-author of the study.
Huntington’s disease (HD) is a neurodegenerative genetic
disorder that affects muscle coordination and leads to cognitive decline and
psychiatric problems. It typically becomes noticeable in mid-adult life, with
symptoms beginning between 35 and 44 years of age. Life expectancy following
onset of visual symptoms is about 20 years. The worldwide prevalence of HD is
5-10 cases per 100,000 persons. Key to the disease process is the formation of
specific protein aggregates (essentially abnormal clumps) inside some neurons.
Link to the study abstract: “Neuronal Properties, In Vivo
Effects and Pathology of a Huntington’s Disease Patient-Derived Induced
Pluripotent Stem Cells” http://www.ncbi.nlm.nih.gov/pubmed/22628015