Promising New Alzheimer’s Treatment Eradicates Tau Tangles

🧠 In this episode, we delve into groundbreaking research from the UK Research and Innovation team that has developed promising new therapies to target and destroy aggregated tau proteins associated with Alzheimer’s disease. This innovative approach could revolutionize the treatment of neurodegenerative diseases.

🔬 **Innovative Treatments Using TRIM21:**
- Researchers have successfully targeted tau aggregates in Alzheimer’s, showing potential for broader application in neurodegenerative diseases like motor neuron disease, Parkinson’s disease, and Huntington’s disease.
- The new therapies selectively target and destroy disease-linked tau aggregates, leaving healthy tau proteins intact.
- The approach also removes already established tau aggregates in mice, not just preventing the formation of new aggregates.

🌟 **Advantages of TRIM21-Based Therapies:**
- TRIM21-based therapies offer two key advantages: they only destroy disease-linked tau aggregates and remove already established tau aggregates in mice.
- The therapies utilize the unique capabilities of a protein called TRIM21, which is a key part of the immune response to viruses.

🧬 **Challenges in Targeting Tau:**
- Tau ‘tangles’ form inside nerve cells and are strongly associated with cognitive decline as Alzheimer’s disease progresses.
- It is difficult for antibody therapies to access tau inside cells, so they do not remove existing tau aggregates inside cells – at best, they prevent aggregates from spreading.
- Other techniques, such as anti-sense oligonucleotides (ASOs), act on all tau in the brain and therefore also remove ‘healthy’ tau, with unknown long-term side effects.

💡 **Innovative Approach Using TRIM21:**
- This new technique utilizes a 2010 discovery from Dr. Leo James’ lab at the MRC Laboratory of Molecular Biology of the role of TRIM21.
- TRIM21 detects antibody-bound viruses and tags them for destruction by the cell’s proteasome.
- By switching out antibodies that bind viruses for antibodies that bind to tau, TRIM21 was re-directed to send tau aggregates to be destroyed by the proteasome.

🔬 **Development of New Tau Aggregate Therapies:**
- Scientists have used TRIM21 to create two new therapies to target tau aggregates.
- The first therapy, ‘RING-nanobody’, combines a tau-binding nanobody with the TRIM21 RING.
- The second therapeutic, ‘RING-Bait’, has the TRIM21 RING joined to a copy of the tau protein itself, acting as bait to incorporate TRIM21 RING into the aggregate.

📊 **Promising Results in Mice Models:**
- The researchers delivered the DNA encoding the TRIM21 therapies into cells containing aggregated tau and found it cleared the tau tangles, leaving ‘healthy’ tau undamaged.
- Elderly mice with tau protein aggregates were injected with a single dose of the gene therapy vector containing either the treatment or a placebo.
- Within a few weeks, there was a significant reduction in the amount of aggregated tau in the brain cells of the treated animals.
- Mice given the RING-Bait treatment showed significantly better motor function, as assessed by an AI program that scored how well they ran.

🌟 **Implications for Future Neurodegenerative Disease Therapies:**
- The RING-Bait approach reduces disease severity in model systems, suggesting that the selective removal of tau aggregates is a valid therapeutic approach.
- The beauty of RING-Bait lies in its broad adaptability and the potential to tackle other conditions characterized by the accumulation of pathological protein clusters.

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