Ohio – In a new study, researchers with The Ohio State University Wexner
and Nationwide Children’s
are now creating personalized model systems for patients with Amyotrophic
lateral sclerosis (ALS, also known as Lou Gehrig’s disease) by using skin cells
collected from patients at Ohio State’s ALS/MND Clinic.
study led by Dr. Stephen J. Kolb of the Department of
Neurology at Ohio State’s Wexner Medical Center and Dr. Brian K. Kaspar of The Research
Institute at Nationwide Children’s Hospital, is published in PNAS.
conversion is a recently established method to generate neuronal progenitor
cells (NPCs) from skin fibroblasts in a fast and efficient manner. In this
study, researchers show that direct conversion can be used to model
neurodegenerative diseases such as ALS. Because the origin of ALS is mainly
sporadic with unknown cause, methods to model the disease are urgently needed.
produced NPCs are differentiated into astrocytes, which are involved in motor
neuron death in ALS. Skin-derived astrocytes show similar toxicity toward motor
neurons as astrocytes from autopsies of patients. This tool now allows studying
ALS while the patient is still alive and can help in testing potential
therapeutics for individual patients.
to model ALS is very difficult because we don’t know what causes it, and most
of our models for neurodegenerative diseases are based on genetic models,” said
Kolb, who is also a member of the Department of Molecular and Cellular
Biochemistry at Ohio State and the Center for RNA Biology at Ohio State’s
Wexner Medical Center. “In neurodegenerative diseases, it is difficult to study
the cells that are involved while the individual with the disease is still
study opens the door to a rapid and efficient manner in which to model an ALS
patient. Within a month we can take a skin fibroblast from a patient and direct
those cells into motor neurons, astrocytes and oligodendrocytes, all cells
involved in this disease,” said Kaspar, who is also a member of the Department
of Neuroscience at Ohio State. “Once we have generated patient specific cells,
we can start to investigate why motor neurons are dying, in our attempts to
understand the underlying mechanisms for what is going wrong in this
study was funded by U.S. National Institutes of Health Grants R01 NS644912-4
and RC2 NS69476-01, a Packard Center for ALS Research Grant P2ALS and the
Helping Link Foundation to Dr. Kaspar’s research program.
is a prime example of clinical and basic scientists working together to create
personalized model systems to model each patient’s individual disease,” said Kaspar.
“We are trying to determine what makes astrocytes toxic to motor neurons in patients
who develop ALS, and how to block that toxicity.”
is ALS Awareness Month, designed to bring attention to this devastating
disorder affecting mainly upper and lower motor neurons in the motor cortex,
brainstem and spinal cord. Patients typically suffer from muscular atrophy and
paralysis, ultimately leading to death within 5 years after diagnosis.
Approximately 5,600 people in the United States are diagnosed with ALS each
year, and it is estimated that as many as 30,000 Americans may have the disease
at any given time, according to the ALS Association.
researchers include Kathrin Meyer, Laura Ferraiuolo, Carlos J. Miranda, Shibi
Likhite, Sohyun McElroy, Samantha Renusch, Dara Ditsworth, Clotilde Lagier-Tourenne,
Richard A. Smith, John Ravits, Arthur H. Burghes, Pamela J. Shaw and Don W.
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Click here for a high-quality
photo of Dr. Stephen Kolb.
here for a high-quality photo of Dr. Brian Kaspar.
Eileen Scahill, Medical Center Communications, Eileen.Scahill@osumc.edu or 614-293-3737.