Slow glial cell transplants the progression of Huntington’s disease

Huntington’s disease has long challenged attempts to rescue the neurons they suffer. A new study in cellular reports shows that the transplantation of healthy healthy -healthy cells to the brains of adult animal models of the disease not only slowed the motor and cognitive deterioration but also the extended useful life. These findings change our understanding of Huntington’s pathology and open a potential path to cells based on adults that already show symptoms.

The glia are essential caregivers of neurons. The restoration of healthy glial support, even after the symptoms begin, could restart the expression of the neuronal gene, stabilize synaptic function and significantly delay the progression of the disease. This study changes Huntington’s perspective of a vision centered on neurons to one that shows a fundamental role for glial pathology in the conduction of synaptic dysfunction. It also tells us that the adult brain still has the repair capacity when it is directed to the correct cells. “

Steve Goldman, MD, PHD, co -director of the center of the University of Rochester for translational neuromedicine and the main author of the study

Huntington’s disease: beyond neurons

Huntington’s disease is a hereditary brain disorder caused by a mutation in the Huntingtin gene. This mutation leads to an abnormal protein that gradually damages nerve cells, particularly in a region called striatum, causing movement problems, mood changes and cognitive deterioration.

The scientific approach of this disease has traditionally focused on saving or replacing affected neurons, but decades of research in the Goldman laboratory have shown that brain support cells calculate the glia that plays a crucial role in how the disease develops.

Once it is considered mere “glue” that holds the neurons in its place, it is now known that the glia regulates neuronal health, controls inflammation and maintains the chemical balance of the brain. In Huntington, the glia becomes dysfunctional and can contribute to neuronal damage. By replacing the sick glia with healthy, scientists hope to restore the support environment that neurons require to function properly, potentially preserving the nerve cells that are lost in the disease.

Healthy glia transplant to symptomatic mice

The researchers used R6/2 mice, a well -established model of Huntington’s disease that develops motor and cognitive symptoms similar to those observed in people. At five weeks of age, when the symptoms have just begun, but before a severe decrease, these mice received injections directly in their strata of human progenitor cells, early elapl that can mature in different types of glial cells. The mice were tested in tasks that measure coordination, movement, memory and anxiety.

The team used the Single Core sequencing to see what genes were on or deactivated in the neurons of the treated mice. They also labeled individual neurons with a modified rabies virus to visualize their branch (dendrites) and connection points (thorns).

Of motor improvements to synaptic restoration

The treated mice showed a clear delay in motor and cognitive deterioration and lived several weeks longer than unrelated HD mice.

Neurons in R6/2 mice normally lose the expression of genes involved in the maintenance of functional synapses, connections between nerve cells. After the glial transplant, many of these genes effectively turned on. In addition, while neurons in mice that model Huntington’s disease generally have fewer branches and thorns, in Huntington’s mice received healthy glia, dendritic branch and column density are recovered to levels that approach normality.

“Although the treatment began after the symptoms appeared, significant improvements were still observed in the light of adult intervention potential,” said the study co -author, Abdellatif Benraiss, PHD, of the Medical Center of the University of Rochester. “This study shows that focusing on glial health in this case by transplanting healthy cells can significantly affect the progression of the disease, not only in newborn models but also in adults that already show symptoms.”

Expand and refine cell -based strategies

Researchers believe that healthy support cells could become part of a multiple treatment strategy, either alone or together with an approach aimed at genes. Future research must determine optimal delivery, dosage and time for this strategy. However, beyond that, combining glial replacement with other therapies, such as reducing mutant expression of hunting and replacing lost neurons, can generate even greater benefits.

“While mice models do not capture all aspects of human Huntington disease, these findings expand the therapeutic landscape to include replacement or glial repair as an attractive potential treatment strategy,” Goldman said.

Additional co-authors include the authors of the authors Carlos Villanueva and Nguyen Huynh, as well as John N. Mariani, Benjamin Mansky, Ashley Tate, Syshoj Lorenzen and Devin Chandler-Militello with the center of translational neuromedicine, which consists of labs at the University of Rochester and the University of the University of Copenhage. The investigation was supported with funds from the Lundbeck Foundation, the Novo Nordisk Foundation, healthy Biotechnology, the National Aging Institute, the Chdi Foundation and the Golf Classsel of Huntington’s disease.