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
In its sixth year, the broadcaster's coverage has become a global brand and ...
01/06/2026
Designed to solve a common problem in broadcasting, the automated workflow detects, identifies, removes, and documents copyrighted music
AudioShake has introdu...
01/06/2026
The sports-analytics company combines its data with proprietary AI to help leagu...
01/06/2026
Category line-up & sponsors announced
Photo: Paul Clarke
The Production Music Awards (PMA) have announced that submissions are now officially open ahead of...
01/06/2026
New hybrid sample/synthesis instrument revealed
Excite Audio have just released the latest instalment in their Evolve series, which has been developed in co...
01/06/2026
Latest TONEX expansion captures three rare vintage amps
The newest addition to IK Multimedia's ever-growing TONEX line-up introduces a set of three incr...
01/06/2026
Musically intelligent soft synth gets upgraded
Scaler Music will be probably be best known to many for their music theory tools, but their product range al...
01/06/2026
SBS confirms its broadcast sponsors for FIFA World Cup 2026
1 June, 2026
Media releases
SBS has secured Hyundai, Hisense, Macca's, Rexona, bet365, Com...
01/06/2026
Rohde & Schwarz Satellite Industry Days 2026 guided by the motto From Earth to ...
01/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/06/2026
Marshall Electronics is showcasing a comprehensive lineup of next-generation POV cameras, purpose-built to power today's connected AV environments, at InfoC...
01/06/2026
Adobe Announces Concept to Vector
Deepa Subramaniam June 1, 2026
0 Comments
One of the biggest frustrations we hear from designers is how difficult it...
01/06/2026
Vampire Feature Night Patrol Graded with DaVinci Resolve Studio
Brie Clayton June 1, 2026
0 Comments
Colorist shapes dark, gritty tone for horror thri...
01/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/06/2026
Mardi 2 juin 14h00
FilmLight (ARRI), 10 rue Ren Boulanger, 75010 Paris
Rejoignez-nous pour d couvrir comment FLAPI (l'API FilmLight) peut transformer e...
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...
31/05/2026
Olivia P rez-Collellmir to Premiere Original Work at Gaud Centennial in Barcelona The Berklee graduate and faculty member will debut her choral symphony with...
31/05/2026
Back to All News
Netflix Wins 15 Awards at the Canadian Screen Awards - See Pho...
31/05/2026
Taiwan is home to more than 500 NVIDIA ecosystem partners. More than 1 million N...
31/05/2026
As factories move from isolated automation to plant-wide intelligence, manufacturers need AI systems that can connect live machine signals, quality systems, wor...
31/05/2026
The NVIDIA AI Cloud ecosystem is accelerating the global buildout of AI factory infrastructure. Partners are expanding capacity to meet growing demand from ente...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Zero in on one that says yes (and no)
Andy Marken May 29, 2026
0 Comments
Hero image courtesy of Deposit Photos
For content creators the most difficu...
29/05/2026
With InfoComm 2026 just weeks away, NDI is giving attendees plenty of reasons to...
29/05/2026
Reaffirming a partnership that has defined Canadian sports broadcasting since 19...
29/05/2026
Mobile/tablet is No. 2 device for watching TV, suggesting that the sports-production industry needs to take another look at the format
Ring Digital's Sprin...
29/05/2026
Berliner Ensemble, one of Berlin's five major theater companies, has expande...
29/05/2026
Solid State Logic will showcase its new compact, fly-away TCA Tour audio product...
29/05/2026
Gerald (Jerry) Pierce, a pioneering technologist who helped shape the digital transformation of the motion picture industry, passed away last month on April 12 ...
29/05/2026
Paramount+ will be the English-language U.S. home for Barclays Women's Super...
29/05/2026
Further strengthening its virtualisation strategy to fully support broadcasters ...
29/05/2026
Swiss broadcaster Canal Alpha has deployed Harmonic's award-winning, software-based XOS Advanced Media Processor to modernize playout operations across cant...
29/05/2026
PTZOptics will showcase a new generation of intelligent video workflows at InfoComm 2026, June 17-19, Las Vegas. Visitors to booth N8227 will see how PTZOptics ...
29/05/2026
Arizona's Family has launched the Arizona's Family Sports (AZFS) streaming app, a new direct-to-consumer destination for live, local sports. The app is ...
29/05/2026
Starting in 2027, DAZN will be the exclusive home of The Canadian Football Leagu...
29/05/2026
Comcast Business has detailed the advanced network infrastructure it has deploye...
29/05/2026
In two-day event, leaders from academia and industry explored solutions to chall...
29/05/2026
The Basketball Tournament (TBT), now entering their 13th year of competition, ha...
29/05/2026
Roku has launched FOX One as a Premium Subscription on The Roku Channel in the U.S. Roku customers can now subscribe to FOX One using their Roku account for liv...
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.
