
Scavenger' cells in the nervous system linked to rare genetic disease Calibr, the drug development arm of Scripps Research, and other collaborators find microglia play a critical role in SMA disease progression.
September 30, 2022
LA JOLLA, CA Spinal muscular atrophy (SMA) is a devastating, rare genetic disease that causes muscle weakness and eventually atrophy all throughout the body. Scientists at Calibr, the drug development arm of Scripps Research, and additional partners have now identified how a critical immune cell known as the microglia impacts SMA.
Published in Glia in July 2022, the findings provide a foundational understanding of SMA and how the interconnected neuro-immune network influences the disease. These insights could help lead to more effective medicines that target the newly discovered pathways.
While there are three drugs currently on the market to treat SMA, they can be toxic and aren't completely effective at alleviating the life-threatening nature of the disease, says co-first author Zaida A. Gloria, a principal scientist at Calibr. As our discoveries indicate, we're beginning to understand the reason is because of just how multi-faceted the disease is. There's now promise in creating medicines that target these additional pathways, while improving lifespan and overall quality of life for patients.
SMA is characterized by a deletion or mutation in SMN1, the gene that produces the survival motor neuron (SMN) protein. Without this protein, the muscles that control activities like breathing, swallowing and walking begin to weaken. If left untreated, most patients with SMA don't survive past two years of age.
While SMA research has historically always centered on enhancing SMN protein expression, the researchers were interested in the supportive roles of other immune cells instead, such as the microglia. The microglia are cells responsible for eating up' dying cells and debris (a process called phagocytosis); migrating around the central nervous system; and sending chemical messengers to recruit additional helper cells to injury sites.
The microglia can be thought of as the nervous system's scavengers and surveyors they call out to the immune system if something is wrong or needs more attention, says co-first author Guzal Khayrullina, PhD, Uniformed Services University of the Health Sciences (USUHS) neuroscience graduate. We wanted to understand how reduced levels of SMN impacts this cell, as very limited research has specifically focused on this question before.
In the study, the researchers utilized mice with low levels of SMN protein, as well as induced pluripotent stem cells (iPSCs) taken from patients with SMA. iPSCs are made by taking a person's skin or blood cells and then reprogramming them back into their earlier, native state before they've become specialized into a specific cell type. This was an important component of the study, as there is not much work focusing on microglia differentiated from SMA patient-derived iPSCs.
In SMN-deficient mice, the team found the microglia in the lumbar region of the spinal cord have a rounded shape with reduced processes, which suggests these cells are in an activated state. By studying the microglia differentiated from SMA-patient iPSCs, they also saw that the SMN-deficient microglia had increased cell migration and phagocytosis. Taken together, these activities could potentially impact the SMA disease pathology overall.
These discoveries solidified our theory that SMA is not just a disease of motor neurons and is likely influenced by multiple different cell and tissue types, says senior author Barrington Burnett, PhD, associate professor and vice chair for research at USUHS. We can now explore how the SMN protein regulates the communications between microglia and motor neurons and the contributions of this interaction to the disease progression, and as a result, develop additional therapies that can make currently available treatment options even more effective.
The researchers plan to further examine the complex nervous and immune system networks involved in SMA, as well as study an additional brain cell type called astrocytes shown to be implicated in the disease.
The study was funded by the Vanier CIHR Doctoral Research Award; Frederick Banting and Charles Best CIHR Doctoral Research Award; Canadian Institutes of Health Research; and the National Institute of Neurological Disorders and Stroke.
In addition to Gloria, Khayrullina and Burnett, authors of the study, Survival motor neuron protein deficiency alters microglia reactivity, included Kristen A. Johnson of Calibr; Matthew Stinson, Natalya Belous, Elizabeth M. Bergman, Fritz W. Lischka, Jeremy Rotty and Clifton L. Dalgard of the Uniformed Services University of the Health Sciences; and Marc-Olivier Deguise, Sabrina Gagnon, Lucia Chehade and Rashmi Kothary of Ottawa Hospital Research Institute and the University of Ottawa.
Rare Diseases Calibr
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
27/05/2026
Telestream has announced that its Board of Directors has appointed Benjamin Desbois as Chief Executive Officer, effective July 1, 2026. Desbois, currently Teles...
27/05/2026
ESPN garnered 10 awards; NBC's Sunday Night Football received the Outstandin...
27/05/2026
Matrox Video is celebrating its 50th anniversary, marking five decades of operations from its headquarters in Montreal, Canada. Founded in 1976, the company has...
27/05/2026
Major League Baseball has announced a series of initiatives tied to America's Semiquincentennial, including a national marketing campaign, Fourth of July br...
27/05/2026
Advanced Systems Group (ASG) has announced that Brian Gross has joined the company as an Account Manager on its Audio team, based in the Burbank office. He will...
27/05/2026
Nielsen has released new research on soccer fandom ahead of the FIFA World Cup 2...
27/05/2026
ESL FACEIT Group (EFG) has unveiled a new partnership with TikTok to bring broad...
27/05/2026
FIFA's Oscar Sanchez gives a deeper look to how this tournament will be cove...
27/05/2026
The soon-to-be senior from Charlottesville is building her skills in replay, TD, and even creative content for HokieVision and its ACC Network productions
In t...
27/05/2026
FOX Sports' Mike Davies breaks down the vision for this summer's showcas...
27/05/2026
HBS's Paul King, FIFA's Oscar Sanchez preview how the masses at home wil...
27/05/2026
FOX's MLB coverage dominated the night at the 47th Annual Sports Emmy Awards...
27/05/2026
One of the most memorable Postseasons in baseball history would have had no memo...
27/05/2026
NBC's Sunday Night Football is among the most decorated and most watched programs in the history of television. It added to its jam-packed trophy case on Tu...
27/05/2026
The 2026 Sports Emmys marked a watershed moment for Prime Video Sports. After bu...
27/05/2026
With the Opening Match just over two weeks away, the entire sports-production-te...
27/05/2026
Spotify already brings together listeners' favorite music, podcasts, and audiobooks in one place. Now, we're trialing a new format that expands the cont...
27/05/2026
The best podcast moments deserve more than just a mental note. That's why today, we're making those moments easier to save and share with clips.
Whethe...
27/05/2026
On Purpose is one of the most popular podcasts in the world, known for conversat...
27/05/2026
On May 8, 1,500 of Olivia Rodrigo's top fans gathered in Barcelona's Tea...
27/05/2026
Hybrid design combines large-diaphragm capsule & ribbon
JZ Microphones have teamed up with Grammy-winning producer and engineer Marc Urselli to develop a ne...
27/05/2026
Three new plug-ins inspired by classic tape effects
AIR Music Tech's latest release delivers a set of plug-ins that aim to capture the character, moveme...
27/05/2026
Piano played on the edge of silence
The Crow Hill Company's Vaults collection offers a continual rotation of instruments that are given away for free fo...
27/05/2026
Recreates Moog's iconic Memorymoog polysynth
Arturia's vast software instrument range offers a combination of new and old, with innovative modern so...
27/05/2026
Offers loudness levelling for speech and dialogue
Accentize have built up a solid reputation with their audio-restoration tools, and their latest plug-in is...
27/05/2026
10,000 units strong - The Rohde & Schwarz R&S M3SR Radio 4400 Rohde & Schwarz celebrates a major manufacturing milestone, producing its 10,000th R&S M3SR Radi...
27/05/2026
The XL Converge 300P radio system emerges with a groundbreaking feature set enhancing the mission-critical communications of public safety, federal and critica...
27/05/2026
Pairing Two47 MCX software with existing LTE networks means tailored system upgrades that can save time, money and lives....
27/05/2026
PAC-3 MSE offers improved range, speed, and maneuverability, making it an effect...
27/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
27/05/2026
Star Trek VFX: Recreating John Knoll's Iconic Warp Stars without a Slitscan ...
27/05/2026
Adventure World Uses Blackmagic Replay for Marine Live
Brie Clayton May 27, 2026
0 Comments
Large screen displays and slow motion replays dynamically ...
27/05/2026
Berklee Alumna and Assistant Professor Olivia P rez-Collellmir to Premiere Origi...
27/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
27/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
27/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
27/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
27/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
27/05/2026
Co-founder Dan Castles to transition to Executive Chair; internal promotion reinforces continuity and long-term growth
Telestream, a global leader in media wor...
27/05/2026
Big Blue Marble today announced that its Nakolos platform is the first end-to-end 5G Broadcast solution worldwide to implement the complete feature set introduc...
27/05/2026
Lightware recently hosted the Girls' Day event in April at its headquarters in Budapest, welcoming students for an interactive introduction to engineering a...
27/05/2026
27 May 2026
VEON's Kyivstar and Uklon Launch Ukraine's First Live Testi...
27/05/2026
May 27th, 2026 May 27, 2026
Press Materials Available Here
TRIBECA X Announc...
26/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
26/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
26/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...