Vaccines Against Huntington's Disease (HD)
Huntington’s disease is a hereditary neurodegenerative disease with complex clinical symptoms that not only seriously affects the patient's quality of life, but also causes death after 15-20 years of onset. Developing targeted, effective vaccines is a promising strategy for dealing with the disease. With a proven platform, a dedicated team and more than 10 years of experience in vaccine research, Creative Biolabs has helped vaccine researchers around the world successfully complete their research tasks.
Huntington's Disease (HD)
Huntington's disease (HD), also known as Huntington's chorea, is a hereditary neurodegenerative disease that causes brain cell death. HD is characterized by motor, psychiatric, and cognitive impairment. Symptoms usually appear around the age of 30, but they can also occur in adolescents, and about 8% of the cases are under 20 years old. In addition to genetic factors, about 10% of cases are genetically mutated, that is, the individual autosomal dominant gene Huntingtin (HTT) has been mutated. The expansion of the cytosine-adenine-guanine (CAG) triplet repeats in HTT, which encodes the Huntingtin (HTT) protein, causes abnormalities in the encoded protein (mutant Huntingtin protein - mHTT) and gradually destroys cells in the brain. The specific mechanism is currently unclear. HD can begin at any age, but its symptoms usually become apparent in the 30s and 40s. In the early stages of the disease, the symptoms are very mild and unnoticeable and people with HD tend to underestimate the severity of their condition. The patient usually dies 15-20 years after the onset of the disease, and there is currently no HD cure.
The pathogenesis of HD
The HTT gene on chromosome 4 contains CAG trinucleotide repeats. The amino acid corresponding to the CAG codon is glutamine. When the CAG repeats too much, a polyglutamine tract (PolyQ tract) is produced. In the normal human gene, the polyQ region is less than 36 CAGs, once the glutamine repeats in the HTT protein is 36 or more than 36, protein HTT will be mutated into an abnormal form, mHTT, which also increases the rate of decay of specific neurons in the brain, which in turn affects motor, psychiatric, and cognitive functions. In general, the extent of the impact is related to the number of CAG repeats. HTT is expressed in all cells, but it is most abundant in the brain and testis, and the protein is capable of interacting with proteins participated in transcription, cell signaling, and intracellular transporting. Studies in animal models have found that the function of HTT may be related to embryonic development. In addition, if the expression of HTT is increased, the survival rate of brain cells will also rise, and the effect of mHTT will be weakened. Therefore, scientists believe that the occurrence of HD may be due to the increase of mHTT in the body. Proteins in the form of mHTT are more easily cleaved into small fragments that are prone to misfolding and aggregation, and over time these aggregates form inclusion bodies within the cell and interfere with neuronal function. mHTT can also cause cell death by affecting the function of protein chaperones, caspases, and damaging the energy production of cells. In addition, there are also theories that mHTT can cause mitochondrial dysfunction.
Development of Vaccines for HD
There is currently no cure for HD. Strategies to improve the disease include using gene-cleavage or gene silencing techniques to reduce mHTT levels, increase neuronal survival, replace lost neurons, and improve brain function, etc. As an effective strategy to prevent diseases and infections, the development of HD vaccine is also a research content of scientists. In this regard, vaccination against the HTT/mHTT protein is also being tried. A plasmid encoding the first 17 amino acids of HTT-103 glutamine-GFP (green fluorescent protein) could protect immunized HD R6/2 transgenic mice from developing a diabetic phenotype. In addition, another research has reported that AA1-17, AA49-60, AA74-88 three non-overlapping HTT exon1 derived peptides could induce the strongest immune response when immunizing HD mutant mice in combination, and are capable of eliciting higher level of antibody compared to that produced by immunizing mice with these peptides respectively.
As a hereditary neurodegenerative disease, Huntington's disease not only seriously affects patients' quality of life, life safety, but also threatens the health of the next generation of the patients. The development of preventive and therapeutic vaccines for HD not only relieves and treats the patient's condition, but also saves the patient's offspring from the worry of the disease. Creative Biolabs is a company specializing in vaccine development. Our research team has been developing vaccines for diseases and infections for decades. Abundant experience, professional team, and caring services have made us a leader in the field of vaccines. We therefore harvest a mass of high recognition and praise from vaccine researchers all over the world. If you have any needs in vaccine development, please feel free to contact us!
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