What You’ll Learn
This article breaks down recent research on neuroinflammation (inflammation in the brain) in Huntington’s disease (HD). You’ll discover how brain cells called glia drive inflammation, which biomarkers might help diagnose HD earlier, and new treatments targeting inflammation that are being tested.
A Quick Look at Huntington’s Disease
Huntington’s disease (HD) is a rare, inherited brain disorder caused by a faulty gene called HTT. This gene has extra repeats of a DNA segment (CAG), leading to a toxic protein that damages brain cells. Over time, HD causes involuntary movements (chorea), memory loss, mood changes, and difficulty with daily tasks. Symptoms usually start in adulthood (around age 45), but some people develop it earlier (juvenile HD).
Why This Research Matters
Most HD research focuses on the toxic protein itself, but inflammation in the brain (neuroinflammation) is also a key player. This review pulls together the latest findings on how neuroinflammation worsens HD and how targeting it might slow the disease. For patients and families, this could mean earlier diagnosis, better symptom management, and new treatment hope.
Neuroinflammation in HD: What the Research Shows
1. Brain Cells Called “Glia” Drive Inflammation
Glia are support cells in the brain that keep neurons (nerve cells) healthy. In HD, three types of glia go haywire, fueling inflammation:
- Microglia: The brain’s “immune cells.” Normally, they clean up damage, but in HD, they become overactive, releasing harmful chemicals (like TNF-α and IL-6) that damage neurons.
- Astrocytes: These cells regulate brain chemistry (e.g., balancing glutamate, a brain chemical that excites neurons). In HD, they fail to soak up excess glutamate, causing “excitotoxicity” (neuron overstimulation) and more inflammation.
- Oligodendrocytes: These make myelin, the “insulation” around neurons that helps signals travel. In HD, they produce less myelin, weakening neuron communication and triggering inflammation.
2. The Body’s Immune System Also Plays a Role
HD isn’t just a brain disease—the body’s immune system (peripheral immunity) is overactive too. Studies show:
- Blood cells (like monocytes) in HD patients release more inflammatory chemicals.
- Gut bacteria imbalances may worsen inflammation, linking gut health to brain symptoms.
- Inflammation elsewhere in the body (e.g., in the heart or liver) can “leak” into the brain, making neuroinflammation worse.
3. Biomarkers: Clues to Diagnose and Track HD
Biomarkers are measurable signs of disease. For HD, researchers are testing:
- NfL (Neurofilament Light Chain): A protein released when neurons break down. High levels in blood or spinal fluid predict faster HD progression.
- YKL-40: Made by astrocytes; elevated in early HD, even before symptoms appear.
- Tau and PDE10A: Tau (a brain protein) and PDE10A (a signaling molecule) levels change in HD and may help track brain damage.
4. New Treatments Targeting Inflammation
Several therapies are being tested to calm neuroinflammation in HD:
- C1q Antibodies (e.g., ANX005): Block a protein (C1q) that overactivates microglia. Early trials show it reduces inflammation markers in the brain.
- Laquinimod: An oral drug that calms immune cells. It improved motor function in HD mice and slowed brain shrinkage in small human trials, though larger studies are needed.
- Gene Therapy + Immunotherapy: Combining treatments that lower toxic huntingtin protein (e.g., AMT-130) with anti-inflammatory drugs may work better than either alone.
What This Means for Patients and Families
- Earlier Detection: Biomarkers like NfL or YKL-40 could help diagnose HD before symptoms start, when treatments may be most effective.
- New Hope for Treatments: Inflammation-targeting drugs are in trials, though they’re not yet approved. Ask your doctor about clinical trials.
- Managing Symptoms: Reducing inflammation might ease symptoms like mood swings or movement problems, even if it doesn’t cure HD.
Gaps in Research and Future Steps
While progress is promising, challenges remain:
- Animal models don’t fully mimic human HD, so some treatments that work in mice fail in people.
- We need better ways to measure inflammation in the living brain (e.g., imaging tools).
- Personalized treatments (tailored to a patient’s specific inflammation patterns) may be the next step.
Key Points to Remember
- Neuroinflammation starts early in HD and worsens brain damage.
- Glia (microglia, astrocytes, oligodendrocytes) and the body’s immune system drive this inflammation.
- Biomarkers like NfL and YKL-40 could help diagnose HD earlier.
- New drugs targeting inflammation are being tested, but more research is needed.
Talk to Your Doctor
If you or a loved one has HD, ask your healthcare team:
- How can I track disease progression (e.g., through blood tests for NfL)?
- Am I eligible for clinical trials testing anti-inflammatory treatments?
- What lifestyle changes (e.g., diet, exercise) might help reduce inflammation?
Understanding neuroinflammation brings us closer to better care for HD. Stay informed, and advocate for research—progress is possible.