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...
06/05/2026
Gravity Media Chief RF Communications Engineer Glenn Willems uses Wisycom RF over Fiber and wireless solutions across major cycling events and international mar...
06/05/2026
A Sennheiser Spectera module is now available in Bitfocus Companion and Buttons, enabling direct integration of Spectera with the two software platforms. The mo...
06/05/2026
Ted Turner, the visionary media entrepreneur whose appetite for disruption helpe...
06/05/2026
Peacock is going all-in on the beautiful game - streaming all 104 FIFA World Cup...
06/05/2026
New pricing tiers for vocal/dialogue restoration tool
NoiseWorks Audio's AI-powered vocal and dialogue processing plug-in is now available in three diff...
06/05/2026
Popular mixing & routing software overhauled
Following a recent public beta test, RME have launched the final release version of the powerful mixing and rou...
06/05/2026
New SOS Video Feature
Focusrites ISA C8X is a milestone product that brings together the companys analogue heritage and their expertise in digital audio. Yo...
06/05/2026
Polands Miecznik-class frigates are part of the largest contract in Polish shipbuilding history. (Image Credit: PGZ Stocznia Wojenna)...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Riedel Communications today announced the expansion of its leadership structure as part of a strategic initiative to strengthen both its operational management ...
06/05/2026
For nearly three decades, Veteran Production Sound Mixer and Five-time Emmy Award Winner Dirk Sciarrotta has helped define the sonic identity of the long-runnin...
06/05/2026
ZEISS CinCraft LensCore: Cinema Lens Looks for Compositing
Brie Clayton May 6, 2026
0 Comments
ZEISS announces the launch of CinCraft LensCore, a nove...
06/05/2026
Wisycom Solves Extreme RF Challenges Across Miles of Live Action for Gravity Med...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Narrative Entertainment has partnered with Encompass to deliver high-quality subtitling of its Great! network content using the Altitude Intelligence AI assiste...
06/05/2026
SipRadius, widely recognized for making content processing and connectivity secure and seamless, is proud to launch a dramatic new approach to AI content creati...
06/05/2026
When the broadband and media industry gathers at ANGA COM in Cologne from May 19 to 21, Big Blue Marble will be at the forefront. The international broadcast an...
06/05/2026
Cinegy GmbH, a leading developer of software-defined television technology, is proud to exhibit at MPTS for the first time. Visitors to the stand will discover ...
06/05/2026
Val Jeanty Receives 2026 Doris Duke Artist Award Jeanty, a composer, percussionist, and turntablist, is the fourth Berklee recipient of the prestigious award ...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
When live cycling races and international marathons stretch for miles across cities and countryside, there is no margin for RF failure in live broadcast. As Chi...
06/05/2026
Oberkochen/Germany, May 5, 2026
ZEISS announces the launch of CinCraft LensCore, a novel solution for creating physically based cinematic lens looks for visual...
06/05/2026
06 May 2026
VEON's Kyivstar Authorized to Resell Starlink for Businesses & ...
06/05/2026
UKTV has secured the exclusive rights to the early back catalogue of iconic Australian drama series Neighbours, following a landmark content deal with Fremantle...
06/05/2026
Wednesday 6 May 2026
Sky commissions feature documentary to mark 10th anniversa...
06/05/2026
Wednesday 6 May 2026
Sky and Formula 1 agree long-term partnership across UK, Ireland and Italy
Sky in the UK & Ireland to remain the home of Formula 1 until ...
06/05/2026
Sky Zero Footprint Fund-backed TV campaign launches nationwide, supported by new...
06/05/2026
Wuppertal May 6, 2026
Riedel Expands Leadership Structure, Appoints Marc Engro...
06/05/2026
SAN JOSE, Calif. - May 6, 2026 - Harmonic (NASDAQ: HLIT) today announced its latest broadband innovations for ANGA COM 2026, highlighting its vision for a new e...
06/05/2026
Statement from Rupert Murdoch, Chairman Emeritus, Fox Corporation on Ted Turner&...
06/05/2026
Friday 8 May on RT One and RT Player
Meet the NSPCA team caring for and protecting animals in need in this six-part series
Fly on the wall, six-part series...
06/05/2026
The race to build the world's most powerful AI factories demands networking ...
06/05/2026
How changes to proteins can alter drug interactions for new precision therapies Scripps Research team maps how chemical modifications to proteins affect drug bi...
05/05/2026
Experts from the world of academia, tech, business, politics and media convened for a Thomson Talks at the Cambridge Disinformation Summit in April. It's th...
05/05/2026
Three phones were hardwired for power and transmission to the truck; camera feat...
05/05/2026
The creative studio behind campaigns for the NBA, Fanatics Sportsbook & Casino, ...
05/05/2026
Nielsen has announced results from a co-viewing pilot program covering February&...
05/05/2026
viztrick AiDi, an on-device AI solution developed by Nippon TV, delivered global...
05/05/2026
ARRI has announced Omnibar, a battery-powered, IP65-rated multi-color LED linear...
05/05/2026
Imagine Communications has announced that France T l visions is the first broadc...
05/05/2026
The Women's National Basketball Association (WNBA) and Bell Media today announced a multiyear agreement to broadcast and stream WNBA games in Canada beginni...
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.
