The following is a brief survey of HD-related research published during July-September 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 for HD.
In a July study published in Movement Disorders, Anne‐Catherine Bachoud‐Lévi, on behalf of the Multicentric Intracerebral Grafting in Huntington’s Disease Group reported on the findings of a randomized phase II trial on human fetal cell therapy for HD. 1 The group aimed to determine the safety and efficacy of intrastriatal transplantation of human fetal cells. Unfortunately, severe adverse events were observed in many of the subjects and no clinical benefits were found from the therapy. The researchers speculate that the unfavorable outcome was due to the patients’ bodies rejecting the transplant. This study highlights the difficulties and challenges currently associated with stem cell transplantation as a treatment method.
Advances in Understanding HD
In an August research article published in Science, a group of French researchers aimed to determine if there are alterations in neurodevelopment among presymptomatic mutation carriers of Huntington’s disease.2 This phenomenon has been previously described in mouse and neuroimaging studies, but this group of researchers hoped to observe it in actual human tissue from fetuses with the HD mutation. They observed a number of abnormalities, including abnormal ciliogenesis (formation of small outgrowths on cell surfaces) and changes in cell cycle progression. Their results have far reaching implications, as they seem to suggest more definitively that HD is not only a degenerative disease and also has a neurodevelopmental component.
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 a July study published in Brian Communications, Wasser and colleagues investigated the relationship between the gut microbiome, cognitive function, and clinical outcomes in HD.3 Their first objective was to identify if there exists any differences in the gut microbial communities of healthy and HD individuals. Using rRNA sequencing of fecal samples, the researchers discovered that there were significant differences in the species richness (number of different species) and evenness (a measure of biodiversity) between the control and HD patient population. Furthermore, the researchers established a correlation between these differences and cognitive performance and clinical outcomes. These findings indicate the importance of the gut microbiome in HD and could imply the microbiome as a target for therapeutic interventions, although much more research is needed on the topic.
Biomarkers are defined as a measurable biological trait that can be used to indicate the presence of a disease. Biomarkers are incredibly helpful tools for physicians in order to diagnose and monitor the progression of diseases. As such, research on quantitative biomarkers for HD is an incredibly important medical need.
In a September study published in Oxidative Medicine and Cellular Longevity, a group of researchers from Minzu University of China performed a meta-analysis of blood oxidative stress markers in HD patients and healthy subjects with the hopes of better understanding the biomarker.4 In their comprehensive meta-analysis of 375 HD patients and 447 HC subjects, they discovered that three blood oxidative stress markers, lipid peroxidation products, 8-hydroxyguanosine levels, and glutathione peroxidase activity, were all dramatically elevated in HD patients. Other biomarkers, such as cholesterol, high-density lipoproteins, low-density lipoproteins, and triglycerides were not significantly different between groups. This study clarified previously inconsistent and unclear associations between blood oxidative stress markers and HD.
- Bachoud‐Lévi, A.C., “Human Fetal Cell Therapy in Huntington’s Disease: A Randomized, Multicenter, Phase II Trial”. Movement Disorders.
- Barnat, M., et al., “Huntington’s disease alters human neurodevelopment”. Science.
- Wasser, C., et al., “Gut dysbiosis in Huntington’s disease: associations among gut microbiota, cognitive performance and clinical outcomes”. Brain Communications.
- Tang, Q., et al., “Blood Oxidative Stress Marker Aberrations in Patients with Huntington’s Disease: A Meta-Analysis Study”. Oxidative Medicine and Cellular Longevity.