In a groundbreaking study, Ben Emery, Ph.D., and Gregory Duncan, Ph.D., have successfully developed innovative mouse models that corroborate the critical link between the inability to repair the myelin sheath surrounding nerves and subsequent neuron loss. These newly created models not only contribute significantly to the ongoing research endeavors of the Emery lab but will also serve as invaluable resources for fellow scientists working on multiple sclerosis (MS) and related demyelinating diseases. (OHSU/Christine Torres Hicks)
Multiple sclerosis is a debilitating neuroinflammatory disease affecting nearly 3 million individuals globally, a condition marked by the progressive loss of myelin—the vital fatty layer that encases nerve cells in both the brain and spinal cord. Chronic degradation of this protective myelin sheath endangers neurons, leading to an alarming increase in disability for individuals diagnosed with demyelinating conditions such as MS.
Research indicates that the chronic loss of myelin results in profound damage to nerve fibers, yet the underlying mechanisms that cause neuron damage remain poorly understood. This study seeks to unearth the complexities involved in this neurodegenerative process.
“Either by pharmacologically or genetically blocking this pathway, we could prevent the death of neurons in these chronically demyelinated mice,” emphasized Ben Emery, Ph.D., the corresponding author of the study and Warren Distinguished Professor in Neuroscience Research at OHSU School of Medicine. His insights shed light on the potential for innovative therapeutic approaches targeting neuron survival.
The reason behind the variability in myelin repair rates among individuals remains enigmatic, a disparity that is further complicated by the observation that myelin regeneration occurs more rapidly in standard mouse models than in human subjects. To gain a clearer understanding of this process, researchers genetically modified the mice to obstruct remyelination, thereby creating a model that more accurately mirrors the pathological states observed in human MS patients.
This seminal study examines two distinctive mouse models exhibiting demyelination: one that possesses the ability to undergo remyelination and another that does not, resulting in persistent myelin loss. Although both models present neuronal damage, the non-remyelinating mice display more pronounced neuron death and heightened inflammation. In contrast, the remyelinating mouse model exhibits less neuron death and shows better overall recovery. The lead author, Gregory Duncan, Ph.D., a postdoctoral scholar in Emery’s lab, played a pivotal role in the development of this mouse model and the discovery of the crucial link between protein pathways and neuron death.
“These genetic models that Greg’s really pioneered are going to be useful for not only our lab, but probably many others to test neuroprotective strategies in this ongoing work on MS and other demyelinating diseases,” Emery noted, highlighting the far-reaching implications of their work.
Through their research, they found that the mice unable to remyelinate exhibited increased activity in a specific protein pathway associated with nerve cell death. Notably, when researchers inhibited this pathway, they were able to successfully prevent neuron death in the damaged mice. In contrast, the remyelinating mice did not activate this specific pathway, establishing a direct correlation between the pathway’s activity and long-term myelin loss.
“It might suggest that inhibiting this pathway could be beneficial in preventing neurodegeneration or slowing the progression of MS,” Duncan suggested, emphasizing the necessity of targeted therapies to mitigate potential side effects due to the pathway’s numerous roles in development and regeneration.
The collaborative efforts of Duncan and Emery signify a promising step forward in understanding the intricate mechanisms of neuron damage, paving the way for further investigation into this complex process. Their innovative model will prove essential for future research aimed at unveiling more about neurological damage and recovery.
In addition to Duncan and Emery, the research team included co-authors from OHSU: Samantha Ingram, B.S., Katie Emberley, B.S., Jo Hill, M.S., Michael McCane, B.S., Skylar J. Ferrara, Ph.D., Brittany Stedelin, M.D., Benjamin Sivyer, Ph.D., Sue A. Aicher, Ph.D., Anusha Mishra, Ph.D., Jonathan W. Nelson, Ph.D., and Thomas S. Scanlan, Ph.D., along with collaborators from the University of California, San Francisco.
This research was made possible through generous funding from various organizations, including Race to Erase MS, NINDS, Collins Medical Trust, the National Multiple Sclerosis Society, and the American Heart Association. Duncan received additional support through a postdoctoral fellowship and a career transition award, underscoring the importance of collaborative efforts in advancing scientific research.
All animal research conducted at OHSU is subject to thorough review and approval by the university’s Institutional Animal Care and Use Committee (IACUC), which prioritizes both the health and safety of research animals as well as the individuals involved in the care of these creatures. The IACUC ensures that all animal research proposals demonstrate scientific value and justify the use of live subjects.
OHSU is committed to maintaining the integrity of its research processes by actively monitoring and managing any external relationships that its researchers may possess. In this instance, both Scanlan and Emery have significant interests in Autobahn Therapeutics, a company that may have commercial stakes in the results of this research, ensuring transparency in all aspects of their work.
Breaking News: Squeaky Mice Bring Insights into Multiple Sclerosis!
Researchers Ben Emery, Ph.D. and Gregory Duncan, Ph.D. develop exciting new models to tackle MS! (OHSU/Christine Torres Hicks)
Ah, Multiple Sclerosis—a medical conundrum wrestling with the nerve-wracking realities of myelin breakdown—like watching a sad little bubble wrap pop one by one! Nearly 3 million people worldwide are affected, battling with the consequences of demyelination; it’s like a really bad game of “pop goes the weasel,” except the weasel is your nervous system. But thanks to Dr. Ben Emery and the ever-determined Dr. Gregory Duncan at OHSU, we might just have some fabulous new tools—cue the superhero theme music! 🎶
What’s the Big Idea?
According to Emery himself, they’ve created mouse models—because let’s be honest, they’re the real MVPs of medical research—showing a direct connection between the inability to repair the protective nerve covering (that’s myelin, folks) and the loss of neuronal function. Simply put, when the fluffy insulation around your nerves isn’t doing its job, it’s not just your Wi-Fi that suffers, it’s your entire nervous system!
Two Types of Mice: A Tale of Two Models
In a classic “Tale of Two Cities” twist, we’ve got two mouse models on the stage. One has the ability to snuggle back into shape and repair its myelin, while the other? Well, it’s a bit more of a drama queen, wallowing in chronic loss and nerve damage. The researchers found that the mice who lumped it up and fixated on their blown gaskets showed less neuron death. In contrast, the poor creatures that couldn’t fix their fluffy coats were like that friend who keeps complaining about their love life without ever putting in the effort—lots of drama, no wins!
This Is Where It Gets Exciting
Now hold onto your stethoscopes, folks. The study discovered that the unlucky mice that couldn’t remyelinate were also hyperactive, much like kids on a sugar rush, in terms of a particular protein pathway linked to nerve cell death. But fear not! When researchers put a genetic leash on this pathway, BAM!—neuron death stayed away like it was shielding itself from an annoying ex. Emery and Duncan suggest blocking this protein pathway could be your golden ticket to preventing neuron death and potentially slowing down the progression of MS. However, let’s be prudent—dramatic restorations should always come with a side of caution, right?
Why Is This Important?
The implications here are as juicy as a gossip column. The tools developed in this study are not just for Emery’s lab—oh no! They’re for the entire scientific community. This means that scientists worldwide can now play with these models to uncover more secrets about MS and other demyelinating diseases. It’s like giving everyone in the lab a party hat—now everyone’s invited to the solution-finding fiesta!
Meet the Team
We should really give a bow to everyone involved in this groundbreaking research: from the pioneering geniuses like Seeking Ben and Greg (that’s altruism par excellence) to a cast of co-authors who could fill a small city. Hats off folks, hats off!
Ben Emery, Ph.D. – The mastermind behind the magic!
Gregory Duncan, Ph.D. – The wizard of mouse models!
Final Thoughts
As we wrap things up, remember that while these mouse models may help us understand MS and demyelination better, human brains are still a bit trickier than rodent minds. But this study? It’s the first step in overcoming the odyssey of nerve damage and opening doors to new treatment avenues! Now if only they could figure out how to get the mice to actually clean their fluffy coats—think of the possibilities!
Until next time, stay curious, stay informed, and maybe give a nod of respect to your local scientists—they’re on the frontline, battling the bizarre world of neurological maladies one mouse at a time!
Ommunity to explore neuroprotective strategies across a range of demyelinating diseases, potentially leading to groundbreaking therapies for conditions like Multiple Sclerosis and beyond. The genetic models created by Duncan are set to open new avenues in research, making them essential for understanding and combating neurological damage.
The Road Ahead
As the scientific community grapples with the complexities of neuroinflammation and myelin repair, Emery and Duncan’s work stands as a beacon of hope. Their innovative approach highlights the importance of targeting specific protein pathways, a strategy that might one day transform the treatment landscape for MS patients. By leveraging these mouse models, researchers can delve deeper into the mechanisms of neuron survival and repair, creating a pathway paved with promise for future therapeutic interventions.
As we push forward, the enthusiasm in the lab is palpable, much like the excitement trailing a new album drop from your favorite band. With ongoing support from various organizations and collaborative efforts across institutions, the quest to unravel the mysteries of Multiple Sclerosis is gaining momentum. Here’s hoping that the insights gained from our squeaky little friends lead to a brighter future for the millions affected by this condition!
