This article is part of a series of Cure SMA grant announcements being shared throughout the winter/spring.

Cure SMA has awarded a $190,000 research grant to Umrao Monani, Ph.D., of Columbia University, for his project titled, “Genetic suppressors of the SMA phenotype.” Dr. Monani is associate professor of Neurology and Pathology & Cell Biology, and a member of the Center for Motor Neuron Biology and Disease, at Columbia University.

Dr. Monani and his team believe that while SMN repletion is a notable advance in the quest to treat SMA, its effects are muted unless implemented early in infancy. Notably, infant patients who miss this therapeutic “window of opportunity” see considerably less benefit from drug intervention than those administered treatment early. This limitation of SMN-repletion therapies stems, at least in part, from an incomplete understanding of how low SMN protein levels cause motor neuron dysfunction and death. One way to address this void in our understanding of SMA pathology involves the identification of factors that modify the disease.

In Dr. Monani’s study, he proposes to identify genetic factors that modify disease. He and his team have recently identified one such modifier that, when expressed in model mice, dramatically suppresses disease. They have also found that its effects are influenced by the genetic background of the mice being tested—meaning mice with different genetic backgrounds display differences in suppression of disease symptoms. The goal of this project is to map and identify the genetic components responsible for these differences. The outcome will not only inform the basic biology of SMA but could also serve to identify novel targets for improved treatments that may be used in combination with SMN-regulating therapeutics.

Meet Dr. Monani

Tell us about your work?

I am an associate professor of Neurology and Pathology & Cell Biology, and a member of the Center for Motor Neuron Biology and Disease, at Columbia University. I received my B.Sc. from St. Xavier’s College in Bombay, India, and my Ph.D. from Ohio State University.

How did you first become involved with SMA research?

I began studying SMA in 1993 while doing graduate work at Ohio State University. In 1997, I attended my first Cure SMA (then Families for SMA) conference and met the parents of a child with SMA. I was profoundly moved and have been researching the disease ever since, first in private industry and currently in academia in my own laboratory at Columbia University.

What is your current role in SMA research?

My lab uses mouse models to understand the biology underlying SMA, with a goal to eventually find the most optimal treatment for the human disease. We were amongst the first to demonstrate how important SMN is to the development and health of the structures where the motor neurons communicate with muscle cells. We continue to use the model mice to find factors that reduce disease severity without necessarily changing SMN levels.

What do you hope to learn from this research project?

The principal objective of this research project is to exploit differences in the SMA phenotype (characteristics or traits) observed in model mice, as compared to non-SMA controls to identify new genes associated with the disease.

How will this project work?

To identify the novel gene(s) associated with SMA, regions of the genome linked to severe or mild disease severity will be sought. These regions will eventually be narrowed using genetic markers until the specific gene or genes of interest are identified.

What is the significance of your study?

Despite progress in treating SMA, not much is known about how low SMN protein causes neuromuscular disease. The significance of the project stems from attempts to address this important question as a means of improving current SMA therapies by understanding other genes that may be influencing disease severity.

About Cure SMA’s Basic Research Funding

This grant to Dr. Monani is part of $1,100,000 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.