Originally published on April 1, 2014.

Cure SMA is leading the way to a world without SMA by advancing a comprehensive research program, of which basic research is a key component. Cure SMA has awarded 79 basic grants for a total of $9,507,612 in the past 10 years. Dr. Chien Ping Ko at The University of Southern California will receive $75,000 to explore the role of glial cells in SMA.

The Role of Glia Cells in SMA

Objective: The present proposal will investigate the involvement of two types of glial cells (supporting cells for neurons), called astrocytes and microglia, in SMA pathogenesis.
Research Strategy: We will use genetically engineered mice to restore or reduce SMN expression selectively in astrocytes. We will also use cell-based assays to study the mechanisms of neuron-astrocyte interactions and neuron-microglia interactions in SMA.
Significance: The results of the proposed studies would provide a novel concept that, in addition to motor neurons, glial cells may also play a key role in SMA pathogenesis. The elucidation of new roles of astrocytes and microglia in SMA would in turn lead to new therapeutic approaches by targeting these glial cells.
Funding Made Possible by a Generous Donation to Cure SMA from The Dhont Family Foundation.

Meet Dr. Ko:

Who are you?
My name is Chien-Ping Ko.  I was born in Taiwan and came to the US in 1971.  I received my PhD in physiology from Washington University in St. Louis, and did my postdoctoral training in neurobiology at the University of Colorado and then the National Institutes of Health.  Since 1981, I have been a faculty in the Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA.   

How did you first become involved with SMA research?
I have long been interested in how neuromuscular junctions (NMJs) work, form and maintain.  In the middle of 2000s, my research group became interested in whether and how NMJs might be involved in motor neuron diseases.  We first studied amyotrophic lateral sclerosis (ALS), a late-onset motor neuron disease that affects adults.  By reading literatures on various motor neuron diseases, we were intrigued by the possibility of NMJ involvement in spinal muscular atrophy (SMA).  Given that the genetic basis of SMA has been much better characterized and various animal models are available, I thought that my expertise in the NMJ might contribute to better understanding of whether and how defects in NMJs and other nerve connections (called synapses) may play a role in SMA.

What is your current role in SMA research?
We have recently found that NMJs in several muscles (such as neck muscles) are severely defective and that synapses from proprioceptive sensory neurons onto motor neurons in the spinal cord are drastically reduced in a mouse model mimicking the severe type of SMA.  We are now using NMJs in these vulnerable muscles and central synapse loss as benchmarks to test in vivo the effectiveness of certain candidate compounds in this severe mouse model.  We are also characterizing NMJs and central synapses in several new mouse models that are less severe.  In addition, we are testing whether and how glial cells may play a role in the pathogenesis of SMA.  Our ultimate goal is to better understand the fundamental biology of synaptic defects and hope to find treatments to restore these defects in SMA.

2014 Cure SMA Research Mission and Funding

The overall mission at Cure SMA is a world without SMA. Making this happen requires scientific research investments. Thus, our main research goal at Cure SMA is to accelerate the discovery of an effective treatment and cure for SMA by funding and advancing a comprehensive research program, including:

•    Basic Research to reveal the best ways of making SMA drugs,
•    Drug Discovery to make new drugs,
•    Developing Clinical Trial infrastructure to help test new drugs, and
•    Clinical Care Research to improve the quality of life in SMA patients.
In addition to the basic research funding announced in this edition of Compass, Cure SMA will invest in more research in 2014 to advance our vision of a world without SMA. Please be on the lookout for two upcoming Requests for Proposals (RFPs) for additional research funding from Cure SMA in 2014 in the following research areas: 1) Drug Discovery – Overseen by the Translational Advisory Council, and 2) Clinical Care – Overseen by the Medical Advisory Council.