Cure SMA has awarded a $75,000 research grant to Robert Kalb, MD, at Northwestern University Feinberg School of Medicine, for his project, “Effects of diminished SMN on segmental spinal cord innervation of motor neurons.”
Dr. Kalb and his team have conducted studies that indicate that there are abnormal connections to motor neurons in their worm model of SMA. More precisely, they have shown an imbalance of excitatory to inhibitory spinal cord circuitry exists. In this study, they propose to examine this balance in various mouse models of disease.
If the abnormal wiring found in worms is also found in mouse models of disease, fixing these connections could have a positive effect on motor function in the SMA. Furthermore, these connections would represent novel therapeutic targets for drug development.
Meet Dr. Kalb
Who are you?
I was a Biology Major at Wesleyan University and went to Medical School in NYC (at the time called Cornell University College of Medicine). During my Neurology Residency at Yale University, I fed my appetite for basic science research by working in the laboratory of Susan Hockfield in the Section of Neuroanatomy. I was fortunate to get NIH support for postdoctoral research and opened my own lab at Yale in 1990. After about a decade, I moved to the Children’s Hospital of Philadelphia (part of the University of Pennsylvania School of Medicine) where I continued my basic science research into the normal development of motor neurons as well as motor neuron diseases. My lab moved to Northwestern University a few weeks ago. My main research interests are the cellular and molecular biology of neurons in health and disease.
How did you first become involved with SMA research?
My lab became interested in the relationship between molecular pathways that control aging and various neurodegenerative diseases. Over the past ~10 years we have increasingly used the microscopic worm C.elegans in our studies and there is a worm SMN. Loss of function mutations in the worm SMN gene lead a disease model of SMA that is tractable for genetic studies. We uncovered a genetic pathway that prolongs life and enhances motor function in the worm model of SMA and we are now interested determining if this pathway is relevant to mammalian models.
What is your current role in SMA research?
The main focus of my lab’s efforts in SMA research is to determine if what he have learned in the worm is true in mouse models of disease. If so, I think we may be poised to translate that worm to humans.
What do you hope to learn from this research project?
We hope to determine if there are abnormal connections to motor neurons in mouse models of SMA like those we see in our worm model of SMA.
How will this project work?
To look at the “wiring diagram” of connections onto motor neurons, we will use a virus based tracing system. When combined with other tools, this will allow us to precisely map who is talking to motor neurons and whether this is defective in mouse models of SMA.
What is the significance of your study?
If the connections to motor neurons are aberrant in mouse models of SMA, drugs may be designed to make up for the loss of those connections. This could lead to improvement in movement in individuals with SMA.
Basic Research Funding
This grant to Dr. Kalb is part of $1,325,000 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.