Scientists at Northwestern and Case Western Reserve universities have developed the first polymer-based therapeutic for Huntington’s disease, a debilitating illness that causes nerve cells to break down in the brain. This disease is triggered by a genetic mutation that leads to proteins misfolding and clumping in the brain, disrupting cell function and ultimately causing cell death. Patients with Huntington’s disease lose motor skills and cognitive abilities, with most dying within 10 to 20 years of symptom onset.
The new treatment utilizes peptide-brush polymers, which shield proteins from binding to each other, preventing clumps that contribute to the progression of the disease. Initial studies in mice have shown promising results, with neurons being rescued and symptoms reversed without significant side effects. Researchers envision that this therapy could potentially be administered as a weekly injection to delay disease onset or alleviate symptoms for patients with the genetic mutation.
The study, set to be published in Science Advances, addresses the urgent need for effective treatment options for Huntington’s disease, a devastating condition without a cure. The lead researcher, Nathan Gianneschi from Northwestern University, highlights the severity of this disease and the lack of available treatments to reverse or stop its progression. The focus of the therapy is on disrupting the interactions between misfolded proteins, addressing a key aspect of the disease’s pathology.
The development of the polymer treatment builds upon previous research by Xin Qi from Case Western Reserve University, who discovered a protein called valosin-containing protein (VCP) that binds abnormally to mutant Huntington protein, leading to protein aggregates that damage mitochondria within cells. By uncovering a peptide that disrupts this interaction, the team laid the foundation for the current study. The peptide, however, had limitations when used alone, due to its vulnerability to enzyme breakdown and difficulty entering cells.
To overcome these challenges, Gianneschi and his team created a biocompatible polymer that incorporates multiple copies of the active peptide, providing a more effective method of disrupting protein interactions in Huntington’s disease. Through laboratory experiments with mouse models, the polymer treatment showed enhanced stability in the body and prevented mitochondrial damage, leading to improved brain cell health and longer survival in mice with Huntington’s disease. These results give hope for potential future treatments for neurodegenerative diseases.
The successful development of this polymer-based therapeutic for Huntington’s disease represents a significant advancement in the field of neurodegenerative disease research. By addressing the underlying mechanisms of disease progression and providing a way to disrupt harmful protein interactions, the treatment offers new possibilities for delaying disease onset and reducing symptoms in affected individuals. Further optimization and exploration of the polymer’s potential in other neurodegenerative diseases are planned, reflecting a commitment to advancing scientific knowledge and translating research into meaningful clinical outcomes. The personal connection of researchers to individuals affected by Huntington’s disease underscores the drive and motivation behind this innovative approach to treatment.