Cure SMA has awarded a $70,000 research grant to Dr. Christine DiDonato at Lurie Children’s Hospital of Chicago for her project, “Assessing mediators of muscle weakness in SMA mice.”
Individuals with SMA do not produce survival motor neuron (SMN) protein at high enough levels, leading to debilitating and often fatal muscle weakness. One of the key unanswered research questions is where and when SMN needs to be delivered in order to provide benefit to those with SMA.
Through work with a new and unique mouse model, Dr. DiDonato and her team have discovered that increasing SMN in the central nervous system does not completely alleviate the symptoms of SMA, suggesting there are also defects in the skeletal muscles that may need to be addressed. This grant will fund further work with this mouse model to better understand where and how SMA therapies should be targeted.
Meet Dr. DiDonato
Who are you?
I’m a basic science researcher that was born and raised in Akron, Ohio. I now live in Chicago and I’m an Associate Professor in the Department of Pediatrics at the Ann & Robert H. Lurie Children’s Hospital and Northwestern University.
How did you first become involved with SMA research?
I started in SMA research while a PhD graduate student at Ohio State University. At that time the gene responsible for SMA was not known. My thesis project focused on refining the area to search for the SMA causing gene and identify and test candidate genes.
What is your current role in SMA research?
My lab has created a number of mouse models that represent the varying forms of SMA and we are using them and other techniques to understand how SMN functions in both motor neurons and skeletal muscle and what are the downstream consequences of Smn loss and ways in which we can bypass those problems and then we perform pre-clinical studies to determine if they can provide functional benefit in our SMA mouse models as a potential for future therapies.
What do you hope to learn from this research project?
We will study a special SMA mouse that we have generated that has increased SMN levels in its motor nerves and low SMN levels everywhere else. This mouse develops muscle weakness as a young adult and with age the mouse becomes weaker and loses more function. We believe this is specifically due to a problem in the skeletal muscle since the motor nerves appear normal and have normal amounts of SMN.
How will this project work?
We will study the skeletal muscles of these mice and various control mice to determine if there are structural defects within the muscle cell. Specifically, we will determine if SMN is indeed localized to the sarcomere and whether there is a problem with muscle cell fusion.
What is the significance of your study?
Our research using these newly developed mice has uncovered the fact that specifically increasing SMN only within the central nervous system does not completely correct everything, as we have unmasked a skeletal muscle problem. This may have important implications for current therapies in clinical trials and future therapies that are being delivered. Therefore, our work is aimed at better understanding the problems within the skeletal muscle and finding to improve its function.
Basic Research Funding
This grant to Dr. DiDonato is part of $890,000 in new basic research funding that we’re currently announcing. Please see below for links to other recent announcements.
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.