What You’ll Learn Here
This article breaks down a research review about brain-derived neurotrophic factor (BDNF) and its role in Huntington’s disease (HD). BDNF is a "growth factor" that helps keep brain cells healthy. We’ll explain how HD disrupts BDNF, what this means for symptoms, and why scientists are studying BDNF as a potential treatment target.
A Quick Overview of Huntington’s Disease
Huntington’s disease (HD) is a rare, inherited neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. This mutation leads to a buildup of abnormal proteins in the brain, damaging cells over time—especially in the striatum, a region critical for movement and mood.
- Symptoms: Over time, HD causes uncontrollable movements (chorea), difficulty with thinking and memory, and mood changes like depression or irritability.
- Onset: Most people develop symptoms between ages 35–45, but it can start earlier (juvenile HD) in rare cases.
- Prevalence: Affects about 5–14 people per 100,000 in Western countries; currently, there’s no cure, and treatments focus on managing symptoms.
Why BDNF Matters for Brain Health
BDNF is like a "nurturing protein" for brain cells. It:
- Helps neurons grow, survive, and connect with each other.
- Is especially important for striatal neurons—the cells most damaged in HD.
- Supports learning, memory, and mood by keeping brain circuits strong.
In healthy brains, BDNF is made in the cortex (the brain’s "command center") and transported to the striatum. When BDNF levels drop, striatal neurons lose this support and start to die—leading to HD symptoms.
How Huntington’s Disease Harms BDNF
Research shows HD disrupts BDNF in three key ways:
1. Less BDNF Production
The mutant HTT protein (mHTT) blocks the BDNF gene, reducing how much BDNF the cortex makes. Think of it like a factory being shut down—fewer "nurturing proteins" are made.
2. Broken Transport Systems
Normal HTT helps carry BDNF from the cortex to the striatum via "cellular highways" (axons). mHTT clogs these highways, so BDNF gets stuck and can’t reach the striatum.
3. Faulty Signaling
Even if some BDNF reaches the striatum, mHTT messes up how neurons "receive" BDNF. The main BDNF receptor (TrkB) can’t trigger survival signals, leaving neurons vulnerable.
Can Boosting BDNF Help Treat HD?
Scientists are testing ways to restore BDNF levels or fix its signaling in HD. Here are the most promising approaches:
1. Gene Therapy
- What it is: Using viruses to deliver the BDNF gene directly into the brain (e.g., striatum).
- How it works: The virus "infects" cells, making them produce more BDNF.
- Progress: In animal studies, this increased BDNF, reduced brain cell loss, and improved movement and memory. Human trials are still early.
2. Stem Cell Therapy
- What it is: Transplanting stem cells engineered to produce BDNF into the brain.
- How it works: These cells act as "mini factories," releasing BDNF where it’s needed most.
- Progress: In mice, stem cell transplants reduced striatal shrinkage and improved mood and lifespan. More research is needed to test safety in humans.
3. Drugs That Boost BDNF
- Existing drugs: Some approved medications (e.g., the antidepressant sertraline, the multiple sclerosis drug glatiramer acetate) slightly increase BDNF levels. In mice, these drugs improved movement and slowed brain cell loss.
- New compounds: Experimental drugs like pridopidine (a sigma-1 receptor agonist) and 7,8-dihydroxyflavone (a TrkB "booster") are being tested to enhance BDNF signaling. Pridopidine is in late-stage human trials for HD.
4. Lifestyle Changes
- Exercise and enrichment: In mice, voluntary wheel-running and stimulating environments (toys, social interaction) increased BDNF levels and delayed symptom onset. While not a cure, these may support brain health in people with HD.
What This Means for You or a Loved One
- Hope, but patience: BDNF-based treatments are promising, but most are still in animal or early human studies. It may take years before they’re widely available.
- Current care: Talk to your doctor about symptom management (e.g., medications for chorea or depression) and supportive therapies (physical/occupational therapy).
- Clinical trials: Ask your healthcare team about opportunities to join trials testing BDNF-related treatments—this helps advance research!
Gaps in Research & Next Steps
Scientists still need to solve key challenges:
- Delivery: Getting BDNF into the brain safely (the blood-brain barrier blocks many drugs).
- Timing: When is the best time to start treatment? Before symptoms appear (pre-manifest HD) or after?
- Side effects: Too much BDNF could trigger seizures or other issues, so precise dosing is critical.
Key Takeaways
- BDNF is a vital "growth factor" that keeps brain cells healthy, especially in the striatum.
- Huntington’s disease reduces BDNF production, transport, and signaling, leading to neuron death and symptoms.
- Treatments to boost BDNF (gene therapy, stem cells, drugs) show promise in animals, but more research is needed for humans.
- Lifestyle changes like exercise may support BDNF levels and slow symptom progression.
Talk to Your Doctor
Use this information to start a conversation:
- "Could BDNF-related research affect my treatment plan in the future?"
- "Are there clinical trials for HD treatments I should consider?"
- "How can I support my brain health now?"
You know your body best—partner with your care team to stay informed and advocate for your needs.
This article is based on a research review published in Current Neuropharmacology (2024). Always consult a healthcare provider for medical advice.