By Jill Adams | Illustrations by Gordon Studer
Basic Research Briefs
How Herniated Discs Lead to Chronic Pain & Disability
Understanding how spinal discs — soft cushions tucked between the vertebrae — function is crucial to understanding back pain. With injury or age-related degeneration, the disc’s soft center bulges out and presses on nerves, resulting in pain.
A new animal model of disc pathology may provide important answers to disc herniation, according to recent research led by Makarand Risbud, PhD, James J. Maguire Jr. Professor of Spine Research.
In the study published in Science Advances, Dr. Risbud and his colleagues, including a former MD, PhD student Emanuel Novais and recent PhD graduate Olivia Ottone, describe a specific strain of inbred mice that form bulging or herniated discs naturally. Previous models have used injury to actively trigger the condition in mice. But this does not necessarily mimic the spontaneous disease process seen in people, including cellular changes and altered immune responses.
The researchers detected changes in the immune system that occurred prior to the disc troubles. This was surprising because immune responses are typically thought to come after injury or infection. Dr. Risbud will continue to study whether this immune dysregulation is triggering disc herniation in some way.
The new animal model might also reveal how disc problems can progress to chronic pain. “Most herniated discs resolve, but some lead to chronic pain. We do not yet understand why,” says Dr. Risbud.
A Key Protein Sheds Light on Huntington’s Disease
By Marilyn Perkins | Illustrations by Gordon Studer
Huntington’s disease is a genetic disorder that kills nerve cells in the brain, causing people to lose their cognitive and motor abilities. Recent research published in Nature and led by biochemistry researcher Anna Pluciennik, PhD, is revealing new molecular pathways behind the disease. The research team included graduate researcher Fenglin Li, research associate Ashutosh Phadte, and postdoctoral research fellow Mayuri Bhatia.
Huntington’s is characterized by an abnormal repeating sequence in the DNA. As people with Huntington’s age, this sequence gets longer, causing DNA strands to misalign. This creates extra loops in the DNA, leading to the production of a toxic protein that eventually kills nerve cells.
Using an electron microscope the team was able to visualize a protein previously implicated in the disease called FAN1 acting like a pair of scissors, snipping off extra loops of abnormal DNA. To do this, FAN1 teamed up with another protein, called PCNA, forming a stable complex. Dr. Pluciennik found that mutations associated with earlier disease onset also made the FAN1-PCNA complex less stable and therefore less effective at removing extra pieces of DNA.
“Based on our research, if we make the FAN1-PCNA complex more stable, it could be protective and delay disease onset,” says Dr. Pluciennik, a member of the Sidney Kimmel Medical College. “This positions the complex as a promising therapeutic target.”