University of Pittsburgh researchers have discovered a novel method to disrupt pathological protein inclusions, which are a hallmark of many degenerative diseases such as ALS, FTD, Alzheimer’s, and Multisystem Proteinopathy. By utilizing nucleic acids and nucleic acid analogs, they have shown that these inclusions can be prevented. This improvement could lead to new therapeutic strategies for treating these diseases.
Description
Intracellular protein inclusions are commonly found in neurodegenerative diseases and are often composed of RNA/DNA binding proteins. The researchers discovered that these inclusions form when the proteins are not bound to nucleic acids. By adding RNA substrates or sequences with high affinity for specific RNA/DNA binding proteins, such as TDP-43, they were able to prevent the formation of these inclusions in live cells. This method leverages the natural binding properties of nucleic acids to disrupt the aggregation process, offering a targeted approach to treating proteinopathies.
Applications
- Therapeutic development for neurodegenerative diseases
- Research tool for studying protein aggregation
- Potential treatment for ALS, FTD, Alzheimer’s
Advantages
This innovative approach provides a targeted method to disrupt protein inclusions without affecting other cellular pathways, reducing the risk of off-target effects. It leverages existing knowledge of RNA/DNA binding proteins and their interactions, making it a feasible and promising therapeutic strategy. Additionally, the use of oligonucleotide therapy is already established in treating other conditions, such as spinal muscular atrophy, which supports the potential for rapid development and clinical application.
Invention Readiness
The technology has been validated in vitro, demonstrating the ability to prevent the formation of protein inclusions by adding specific RNA sequences. The researchers used an optogenetic method to generate protein inclusions and showed that these inclusions only formed when the RNA binding protein TDP-43 was not able to bind its RNA targets. By adding a specific RNA sequence with high affinity for TDP-43, they successfully prevented the formation of aggregates. The next steps include in vivo studies to confirm the efficacy and safety of this approach in animal models.
IP Status
https://patents.google.com/patent/US20210169914A1
