The following is a brief survey of HD-related research published during October-December 2020:
Stem Cell Therapy
Stem cell therapy refers to a method that promotes the repair response of diseased tissue using stem cells, or cells with the potential to differentiate into many different types. This therapy has attracted a lot of interest as a potential therapeutic strategy.
In a study published in December in Neuroscience Research, a group of Iranian researchers explored the use of stem cells derived from dental pulp in treating HD in rats. 1 Using administration of a chemical called 3-nitropropionic acid that results in progressive locomotor decline, the group created a rat model of HD disease. Then, the researchers implanted dental pulp stem cells to investigate potential ameliorative effects. Their findings were promising; the transplants were well accepted and improved motor skills. Using a process called histological analysis, where thin slices of tissue are stained and examined under a microscope, the researchers observed that the stem cells hindered shrinkage of the striatum in the rat brains. Additionally, stem cell implants decreased the expression of pro-inflammatory cytokines responsible for brain damage in HD rats. This study demonstrates the potential for dental pulp stem cells in the treatment of HD, but significant investigation is still required.
Advances in Understanding HD
Gut dysbiosis refers to an imbalance of intestinal microorganisms. These microorganisms are vital to our health, and such imbalances can have implications towards overall health. In addition to the classic HD clinical symptom triad of cognitive, motor, and behavioral disturbances, gastrointestinal disturbances such as diarrhea and gastritis (stomach inflammation) are recognized as clinical attributes of HD. There is growing interest in the role that the gut microbiome, or collection of microorganisms, plays in HD manifestation.
In an October study published in Nature Scientific Reports, a group of Swedish researchers investigated the role of tight junction (TJ) proteins in maintaining the barrier between the intestines and systemic circulation (the blood supply) in a mouse model of Huntington’s Disease. 2 Normally, TJ proteins play the vital role of preventing bacteria moving from the intestines to the rest of the body. However, it has been established that in Parkinson’s patients, this barrier is weakened, leading to leaky gut syndrome. The resulting imbalance in gut bacteria can cause a lot of issues. This group of researchers aimed to see if a similar phenomenon can be observed in a mouse model of HD. They found that although TJ protein levels were normal in HD mice, there was an observable increase in gut permeability and significantly altered gut bacteria levels. Their results indicate the relevance of increased intestinal permeability and dysbiosis in HD; however, further studies are needed to examine the clinical effects of such changes.
Computational methods have and continue to play an increasingly important role in improving our understanding of the pathophysiology of HD and discovering novel therapeutic strategies. One such method involves statistical analysis on gene expression measurements over time in order to identify genes that are associated with specific HD disease metrics (such as severity). This technique greatly increases our understanding of the genetic basis of how HD works and has the potential to inform specialized therapeutic strategies. However, a significant impediment to obtaining useful information from such analyses surfaces when different technologies are used to measure gene expression at different time points, creating data inconsistencies.
In a December study published in Biometrical Journal, Fuady and colleagues tackled this problem by developing a novel method of modeling associations between gene expression and disease indicators in cases where two different technologies were used to obtain data at different time points. 3 Using their technique, the research group was able to successfully identify specific genes that were expressed in correlation with severity of HD. Their technique opens up possibilities for analyzing gene expression data that was suboptimally collected.
Given the genetic nature of HD, there exists the possibility for predictive testing. Those who are at risk of HD have the option to choose whether or not to get genetically tested. When testing protocols were first developed, it was predicted that a significant proportion of at-risk individuals would undergo the test, however, testing rates have remained unexpectedly low across cultural contexts. This phenomenon prompted a group of French scientists to explore a comparison of familial attitudes towards testing over the past 20 years in a recent December study. 4 While the percentage of the population seeking testing has remained relatively constant, the researchers found significant differences in the motivations to do so. 20 years ago, the main reason for getting tested was to prevent genetic transmission to children. Now, the main motivation is autonomy and the right to know. These findings offer incredible insight into historical motivations to undergo genetic testing and can inform policy decisions moving forward.
- Eskandari, N., et al., “Transplantation of human dental pulp stem cells compensates for striatal atrophy and modulates neuro-inflammation in 3-nitropropionic acid rat model of Huntington’s disease Author links open overlay panel.” Neuroscience Research.
- Loredan, S., et al., “Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease.” Scientific Reports.
- Fuady, A., et al., “Statistical method for modeling sequencing data from different technologies in longitudinal studies with application to Huntington disease.” Biometrical Journal.
- Pierron, L., et al., “Informing about genetic risk in families with Huntington disease: comparison of attitudes across two decades.” European Journal of Human Genetics.