The State of SMA – Toward Improved Therapeutics and Care

September 7, 2023 / No Comments / Uncategorized

Each year, Cure SMA collaborates with our Scientific Advisory Board to plan a Special Session that will be held during the Annual Research & Clinical Care Meeting. This Special Session is designed to focus on a topic that is currently of great interest to both researchers and clinicians. This year’s Special Session, “The State of SMA – Towards Improved Therapeutics and Care,” was an opportunity to better understand the current population of individuals living with SMA and their unmet needs. A main goal of the session was to discuss how these unmet needs and remaining questions about clinical care should inform the next phases of basic research.

In this year’s two-part Special Session, speakers were invited to present an overview of the current state of research or care in their area of expertise. Each speaker focused on outstanding questions or issues in their field, with the goal of stimulating conversation among session attendees during the Panel Discussions at the end of each part of the session.

Below is a summary of each presentation in this year’s Special Session.

Click on the following links for summaries of the Basic Research Session and the Clinical Research and Clinical Drug Development Sessions.

Part 1: The Evolving SMA Patient Population: Unmet Needs and Impact of Early Treatment

Moderator: Charlotte Sumner, MD ~ Johns Hopkins University School of Medicine

1. Introduction to the Session

Charlotte Sumner, MD ~ Johns Hopkins University School of Medicine

& Stephen Kolb, PhD ~ The Ohio State University Wexner Medical Center

2. SMA in the United States: Perspectives from Multiple Real World Data Sources

Lisa Belter, MPH & Sarah Whitmire, MS/MA ~ Cure SMA

Main Points:

In this presentation, the speakers showed how data from the Cure SMA Community Update Survey, Newborn Screening Registry, and Clinical Data Registry can be used to understand the current population of individuals living with SMA.
In particular, they focused on the impacts of SMA treatment and the unmet needs of the SMA community.

3. Where Are They Now? The SMA Newborn Screening Identified Infants’ Clinical Journey

Crystal Proud, MD ~ Children's Hospital of The King's Daughters

Main Points:

Proud shared her experience in providing care to infants with SMA who were identified via newborn screening. She highlighted both progress and challenges.
Challenges that were discussed among the audience were the incidence of orthopedic complications such as hip dysplasia and scoliosis and how to best treat those conditions.

What’s Next? Drugs in the Pipeline

Thomas Crawford, MD ~ Johns Hopkins Medical

Main Points:

Crawford gave an overview of the drugs currently being tested in clinical trials for use in treating SMA.
He then focused on the investigational muscle drugs that may be used in combination with the FDA-approved, SMN-enhancing therapies such as those in clinical trials being conducted by Scholar Rock and Biohaven Pharmaceuticals.

Panel Discussion

Part 2: The Importance of Understanding SMA Pathobiology and Identification of New Druggable Targets

Moderator: Stephen Kolb, MD, PhD ~ The Ohio State University Wexner Medical Center

1. What Genetics and Biochemistry Have Told Us about SMA and SMN: Where We Go from Here

Arthur Burghes, PhD ~ The Ohio State University Wexner Medical Center

Main Points:

Burghes explained that in the first era of genetic discovery for SMA, SMN1 was identified as the gene responsible for SMA, and SMN2 was revealed to be both a powerful modifier of disease and a target for SMA treatments.
He went on to describe how using SMN mutants (copies of the SMN gene that have changes in the genetic sequence) can help researchers better understand the functions of the SMN protein.

2. The Role of SMN at the Neuromuscular Junction: Known Functions and Remaining Questions

Umrao Monani, PhD ~ Columbia University Medical Center

Main Points:

Monani described a novel role for the SMN protein in which it is involved in the assembly of what is known as the “SNARE complex” at the neuromuscular junction. Knowing that the SMN protein plays this role helps explain how low levels of SMN protein, which is expressed everywhere in the body, result in motor neuron disease.
He also highlighted future experiments that would give more insight into how the disruption of SNARE complex assembly in SMA results in motor neuron death.

3. Understanding Neuronal Vulnerability: Lessons from Mouse Models

Lyndsay Murray, PhD ~ University of Edinburgh

Main Points:

Murray described that while motor neuron loss is a well-understood characteristic of SMA, not all motor neurons are equally vulnerable. Some motor neuron populations are lost early in the disease while others remain intact at the end-stage of disease.
She added that understanding the basis of this selective vulnerability could give critical insight into the factors which allow for certain motor neuron populations to better withstand the low levels of SMN protein in SMA. This insight could in turn help researchers find new strategies to design drugs that protect vulnerable motor neurons in people with SMA.