Cure SMA has awarded a $75,000 research grant to Yong-Chao Ma, PhD, Ann & Robert H. Lurie Children’s Hospital of Chicago, for his project, “Regulation of Motor Neuron Defects by Cdk5 Signaling in SMA”.
Dr. Ma and his team have found that the activity of a protein called Cdk5, cyclin-dependent kinase 5, is significantly increased in motor neurons affected by SMA. In this project they hope to find out why this protein displays increased activity when SMN protein levels are low and to test whether inhibiting the hyperactive Cdk5 activity can be used as a therapeutic strategy for SMA.
The team plans to use a combination of genetic, biological, and biochemical approaches to investigate how increased Cdk5 activity leads to motor neuron degeneration. They will also test reducing the activity of Cdk5 as a therapeutic strategy for rescuing motor neuron defects in SMA mouse models.
The proposed study will provide insights into our understanding of motor neuron degeneration in SMA. The findings could potentially led to the development of new therapeutic strategies that could be used in combination with approaches that work at the SMN level, to treat SMA from all directions for the best chance of a comprehensive and effective therapy.
Meet Dr. Ma
Who are you?
I received my PhD from the Weill Medical College of Cornell University and did my postdoctoral training at Harvard Medical School/Children’s Hospital Boston studying spinal motor neuron development.
How did you first become involved with SMA research?
My lab focuses on research into the molecular mechanisms regulating spinal motor neuron development. This work caused me to ask how dysregulation of spinal motor functions may contribute to SMA.
What is your current role in SMA research?
My group at Northwestern University/Children’s Hospital of Chicago Research Center studies cell signaling and gene expression mechanisms regulating healthy spinal motor neuron functions. Understanding how normal processes are dysregulated could lead to a better understanding of spinal motor neuron degeneration in SMA. To address these questions, my group uses SMA mouse and zebra fish models, human SMA induced pluripotent stem cells, and cultured spinal motor neurons as model systems. We employ a combination of molecular biological, biochemical, and genetic approaches to address this problem. We also collaborate closely with several other laboratories with complimentary expertise to explore novel pathogenic mechanisms and therapeutic strategies of SMA.
What do you hope to learn from this research project?
We hope to learn the role that Cdk5 hyperactivity plays in the degeneration of motor neurons. Understanding how this particular protein contributes to motor neuron loss would lend valuable insight into development of new therapies to prevent motor neuron degeneration in SMA.
What is the significance of your study?
Our study will provide will help us understand more about motor neuron degeneration in SMA. The findings could potentially lead to the development of new therapeutic strategies. These strategies could be used in combination with SMN-enhancing therapeutics, such as Spinraza, to achieve maximal therapeutic benefit.
Basic Research Funding
This grant to Dr. Ma is part of $1.03 million in new basic research funding that we’re currently announcing.
Basic research is the first step in our comprehensive research model. We fund basic research to investigate the biology and cause of SMA, in order to identify the most effective strategies for drug discovery. We also use this funding to develop tools that facilitate SMA research.