In patients with Huntington’s disease, proteins misfold and clump together. Now scientists have designed a polymer that prevents protein aggregates. This is based on animal experiments, where proteins bonded to a polymer instead of each other. Hence, these ‘designer polymers’ disrupt protein interactions in order to preserve cell health.
With the research from Northwestern and Case Western Reserve universities, the treated animals lived longer, behaved more like mice without the disease. Here the treatment successfully rescued neurons to reverse symptoms.
The treated mice also experienced no significant side effects, confirming the therapy is nontoxic and well tolerated.
The breakthrough is the first polymer-based therapeutic for Huntington’s disease. The condition is an incurable, debilitating illness that causes nerve cells to break down in the brain.
Patients with Huntington’s disease have a genetic mutation that triggers proteins to misfold and clump together in the brain. These clumps interfere with cell function and eventually lead to cell death. As the disease progresses, patients lose the ability to talk, walk, swallow and concentrate. Most patients die within 10 to 20 years after symptoms first appear.
The new treatment uses peptide-brush polymers, which act as a shield to prevent proteins from binding to one another.
The treatment needs further testing, however the researchers hope that one day the treatment could be administered as a once-weekly injection to delay disease onset or reduce symptoms in patients with the genetic mutation.
The new study builds on earlier research that identified a protein (valosin-containing protein) that abnormally binds to the mutant Huntington protein, causing protein aggregates. These aggregates accumulate within a cell’s mitochondria, an organelle that generates the energy needed to power a cell’s biochemical reactions. Without functioning mitochondria, the cells become dysfunctional and then self-destruct.
The peptide faced several limitations. Since they are easily broken down by enzymes, peptides have a short lifespan in the body and often have difficulty effectively entering cells. For the peptide to inhibit Huntington’s disease, it needs to cross the blood-brain barrier in large enough quantities to prevent large-scale protein aggregation.
To overcome these obstacles, the researchers developed a biocompatible polymer that displays multiple copies of the active peptide. The new structure has a polymer backbone with peptides attached like branches. Not only does the structure protect the peptides from destructive enzymes, but it also helps them cross the blood-brain barrier and enter cells.
The research appears in the journal Science Advances. The study is titled “Proteomimetic polymer blocks mitochondrial damage, rescues Huntington’s neurons and slows onset of neuropathy in vivo.”
