Cure SMA has awarded a $200,000 research grant to Charlotte Sumner, MD, at Johns Hopkins University, for her project, “Neurofilaments as markers of neurodegeneration in SMA.”

Dr. Sumner and her team are looking at the neuronal-specific cytoskeletal protein neurofilaments (NFs) released during axonal degeneration. These NFs can be measured in blood and/or cerebral spinal fluid (CSF) using highly sensitive single molecule detection systems. In preliminary studies, in the nusinersen ENDEAR trial, NF levels were increased in SMA patients and decreased, but did not normalize after nusinersen treatment. These initial data indicate that NFs are promising novel biomarkers of disease activity and therapeutic responsiveness; however, no studies to date have characterized NF levels in SMA preclinical models in which the timing of drug initiation and drug dose can be readily manipulated.

This grant to Dr. Sumner will allow her team to characterize baseline blood NF levels over developmental time in SMA mice and to determine alterations in the context of tissue-specific increases in SMN expression and SMA therapeutics delivered at different time points and doses. The team will also assess blood and CSF NF levels in SMA patients of different ages before and after Spinraza treatment. Together these studies will provide critical insights regarding the time course of neurodegeneration in SMA and inform strategies to optimize SMA therapeutics.

Meet Dr. Sumner

Who are you?

I am a clinician-scientist who cares for adults with SMA and other inherited neuromuscular disorders. I also direct a research laboratory focused on understanding the cellular and molecular mechanisms that cause SMA and devising strategies to optimize treatments.

How did you first become involved with SMA research?

I first became exposed to SMA research as a postdoctoral fellow under the mentorship of Kenneth Fischbeck. I jumped all in after attending my first Cure SMA meeting in 2002.

What is your current role in SMA research?

We are attempting to better understand the pathologies of motor neurons and other cell types that cause the symptoms of SMA and devise new strategies that can be used in combination with current drugs to maximize therapeutic efficacy.

What do you hope to learn from this research project?

The objective of this application to evaluate blood neurofilament light chain (NF-L) levels as a biomarker of SMA disease activity and therapeutic responsiveness.

How will this project work?

We will measure blood NF-L levels in SMA mice at baseline at different time points and determine changes when SMN is increased in specific cell types or when mice are treated with SMN-inducing therapeutics. We will also determine NF-L levels in patient blood and CSF samples isolated from patients who are initiating nusinersen.

What is the significance of your study?

If successful, these results would provide further insights regarding the time course of neurodegeneration in SMA and the impact of therapeutic intervention. These observations could aid in optimizing therapeutic efficacy of currently available drugs and future therapeutics in SMA patients.

Basic Research Funding

This grant to Dr. Sumner is part of $1,150,000 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.

Past Announcements 

$150,000 to Veronica Pessino, PhD

$150,000 to Laxman Gangwani, PhD