Uncontrollable movements, memory loss, mood changes, and forgetfulness are among the symptoms associated with neurodegenerative diseases, wherein cells in the central nervous system cease functioning or die. Many of these conditions are attributed to the loss or malfunction of glial cells, the supportive cells in the brain. As these ailments manifest in the human brain, they present significant challenges for treatment and research.
However, there is now reason for optimism as recent research conducted at the University of Copenhagen suggests the possibility of new and effective treatments. The study reveals that diseased and aged brain cells can be replaced with fresh and healthy ones, offering potential restoration of normal brain function.
Professor Steve Goldman, from the Center for Translational Neuromedicine at the University of Copenhagen and the senior author of the study, explains the promising findings. By transplanting healthy human glial progenitor cells into the brains of mice previously colonized by diseased human brain cells, the healthy cells exhibit a remarkable ability to outcompete the sick cells. Furthermore, the research shows that when younger cells are transplanted into a healthy brain, they can replace aged cells effectively. This discovery opens up broad possibilities for glial cell transplantation in various disease targets that involve older glial cell populations.
Glial progenitor cells have the remarkable ability to generate two types of cells crucial for brain health: astrocytes, which provide support and safeguard the supply of oxygen and nutrients to neurons from blood vessels while eliminating waste substances, and oligodendrocytes, responsible for producing myelin, the insulating substance found in the brain's white matter.
While the study was conducted on mice, the innovative humanized brain method pioneered by Steve Goldman and his team enabled the examination of human brain cells within a live adult brain. This development significantly increases the likelihood that their findings will be applicable to human patients as well.
"We have made considerable progress in our research. While we must ensure the long-term safety of the transplanted cells, we are confident that we will have the necessary data within approximately a year and a half, once we have this crucial data, we aim to seek approval to proceed with patient trials. If all goes well, I am optimistic that we could begin trials of this approach within the next two years."
Steve Goldman
During the study, the researchers conducted a transplantation of healthy glial cells into the brains of mice that already contained diseased human glial cells.
In previous experiments, the researchers had demonstrated the positive effects of transplanting healthy human cells into mouse models of Huntington's disease. However, to ensure the relevance of their findings to human patients, they needed to ascertain whether the same beneficial outcome could be achieved when replacing human cells with other human cells, specifically within the humanized mouse brain.
Steve Goldman explains the results, stating that the healthy human cells were transplanted into mice that were "humanized" with mutant Huntington-expressing glia. The outcome was striking as the healthy glial cells outcompeted and replaced the diseased glial cells, effectively eradicating the unhealthy glial population.
Similarly, when the researchers attempted to replace non-diseased, healthy but aged glial cells with new cells, they observed the same favorable outcome. The younger cells outcompeted the aged cells, successfully taking their place. These results highlight the potential and effectiveness of glial cell transplantation for treating neurodegenerative diseases and restoring brain function.
According to Steve Goldman, the results of the study revealed a crucial insight. It became evident that the success of healthy cells outcompeting diseased cells in Huntington's disease was not limited to that specific condition alone. Rather, this approach holds immense potential for a wide range of diseases involving older or diseased glial cell populations. The implications are significant, as it opens up possibilities for targeting various illnesses related to glial cells.
These potential targets encompass diseases such as multiple sclerosis and white matter stroke, as well as various neurodegenerative conditions like Huntington's disease, ALS (amyotrophic lateral sclerosis), and some genetic forms of schizophrenia. This discovery marks a substantial advancement in the potential therapeutic applications of glial cell transplantation across a spectrum of debilitating disorders.
The recent research offers promising prospects for the development of new treatments targeting complex diseases.
Steve Goldman emphasizes the potential impact of replacing diseased and aged cells, which could lead to the restoration of normal function in degenerative diseases, as demonstrated in their experimental models of Huntington's disease. This success serves as a proof of principle, encouraging the researchers to explore the application of this approach to other diseases.
They believe that the same strategy could be effective in addressing conditions such as ALS (amyotrophic lateral sclerosis), certain types of frontotemporal dementias, hereditary schizophrenias, myelin diseases, and age-related white matter loss.
Excitingly, the possibility of implementing these new treatments is not distant. The researchers are already planning clinical trials to assess the efficacy of this approach on three different brain diseases. These trials will include testing the treatment's effects on Huntington's disease, as well as two white matter diseases, progressive multiple sclerosis, and Pelizaeus-Merzbacher disease. This represents a significant step forward in the potential transformation of medical care for individuals affected by these challenging neurological conditions. (NGN/NW)
