Anton Blatnik, PhD, at The Ohio State University has been awarded $100,000 for his research project, “Determining Primary Splicing Changes in Spinal Muscular Atrophy.”
Dr. Blatnik’s basic research grant is one of five awarded by Cure SMA in 2022 totaling $525,000.
Meet Dr. Blatnik
Tell us about yourself.
I am a lover of music, hard puzzles, and pursuing a comprehension of biology. In fact, I enjoy hard puzzles and biology so much, I have found my way to being a postdoctoral researcher in Dr. Arthur Burghes’s laboratory at The Ohio State University College of Medicine. I am determined to understand how low levels of SMN protein cause SMA. I received my undergraduate degree in biochemistry from Ohio Northern University in 2012. I thought this was an adequate background for a career as a musician until I read about two researchers at Ohio State, Drs. Arthur Burghes and Brian Kaspar, who were using a viral delivery system to provide gene therapy treatment for SMA. I joined their labs in 2013 as a graduate student, dedicating my focus to understanding SMN function.
In my thesis research, I developed a cell survival assay to test mutant SMN protein function, and I performed a screen to identify the lost function of mutant SMN proteins. I have melded genetic, biochemical, and viral-mediated translational approaches in cells and mice to continue these studies and address new questions. The emphasis of my current research is on RNA processing events, which I study in collaboration with Dr. Guramrit Singh.
How did you first become involved with SMA research?
I applied to the Ohio State Biochemistry Graduate Program with the initial intention of working on viral-mediated gene therapies. My timing couldn’t have been better because the clinical trials of what would eventually become onasemnogene abeparvovec were in their starting phases at Nationwide Children’s Hosptial, and the Burghes and Kaspar lab collaboration was in full swing! This immediate proximity to SMA was lifechanging for me, providing an environment that tangibly connected basic science interests with the needs of patients, and instilling a sense of purpose in pursuing a comprehension of biology.
What is your current role in SMA research?
My current focus is on understanding how low levels of SMN result in SMA, with the long-term aim of helping develop additional treatment options to meet the needs of patients who have suboptimal responses from the current suite of therapeutics. As an academic, understanding SMN functions and the consequences of limiting these functions can shed light on molecular and cellular events performed by every cell. In collaboration with Dr. Guramrit Singh, my current emphasis is on understanding the consequences of limiting the SMN protein’s role in Sm-ring assembly. I aim to build a genetics and biochemical research program with a foundation in SMA and SMN biology to explore RNA processing events in the context of neuromuscular disease.
What are the project goals?
This project aims to address the long-standing question, “Which function(s) of SMN are directly responsible for the development of SMA?” Specifically, I aim to expand the understanding of the role of the SMN protein in Sm-ring assembly.
The SMN protein has a number of functions in cells throughout the body. In SMA there is SMN protein deficiency, disrupting many of the processes that are important for cell health. One such process is Sm protein ring assembly. Sm proteins bind together to form rings that act as the core structures for larger protein complexes. These complexes are involved in processing RNA that is transported out of the nucleus and translated into protein elsewhere in the cell. Although SMN protein deficiency in SMA likely results in reduced Sm-ring assembly, a causal link between reduced Sm-ring assembly and the development of SMA has not been established.
The first aim of this project is to demonstrate that the association of Sm-rings with RNA is dependent on the presence of the SMN protein, and that this association functions as a signal to move these RNAs to specific locations within the cell. The second aim is to establish a causal link between reduced Sm-ring assembly and impaired processing of newly synthesized RNAs.
What will the results tell us?
The three FDA-approved SMA therapeutics all work by increasing SMN protein levels. Therefore, these treatments are referred to as “SMN-dependent.” Combining SMN-independent therapies and SMN-dependent therapies may result in more optimal treatment outcomes. Understanding the different functions of the SMN protein may reveal new strategies for developing SMN-independent treatments.
Importance of Basic Research
Each year, Cure SMA invites scientists from around the world to submit funding proposals for basic research projects that address specific unanswered questions in SMA biology. Our Scientific Advisory Board ranks the submitted proposals on both their scientific merit and relevance to the Cure SMA research priorities. This year, Cure SMA’s top basic research priorities include:
- Learning about the roles the survival motor neuron (SMN) protein plays throughout the body.
- Understanding the details of how SMN-dependent therapies work.
- Finding treatment targets other than SMN.
- Combining SMN-dependent therapies and other treatments to achieve the best possible outcomes.
Special thanks to the Nunemaker Family for partnering with Cure SMA in our quest to invest in research that will focus on ways to enhance muscle strength and function as well as investigating nerve muscle connections and the regeneration of nerves. To achieve these goals, the Nunemakers have generously offered to match all gifts up to $250,000. To join the Nunemakers in investing in the future of SMA, please visit this link.