Written By: Mayukha Kashyap
New research is paving the way for potential treatment options for Huntington’s Disease
Some diseases in the world are genetically inherited from a family member. Some examples include sickle cell anemia, cystic fibrosis, hemophilia, and Huntington’s disease. These diseases are split into two categories: genetic diseases and sex-linked diseases. Genetic diseases occur when genes are mutated, affecting cell function, while sex-linked diseases occur when a gene that controls a specific trait is located on a sex chromosome. Sex chromosomes are categorized as X and Y. Males have the sex chromosome XY, while females are XX. Huntington’s disease is a genetic disease that is known for affecting people in their mid-40s. In other words, if someone were born with the Huntington’s disease gene, they would not know about it until symptoms started showing up in their mid-40s. Symptoms include uncontrollable spasms and dementia.
Huntington’s disease is classified as autosomal dominant. Autosomal means that it affects a cell in the body, while x-linked means it involves a sex cell. If a disease is autosomal recessive, then a person needs to have two recessive alleles for the disease to have it. Heterozygous individuals, or those who have one dominant and one recessive allele, will be carriers of the disease. A carrier can pass the allele for a disease to their offspring but will not have any symptoms. Because Huntington’s disease is autosomal dominant, a person only needs to have one dominant allele for the disease to be passed. Thus heterozygous individuals are also affected by the disease rather than being carriers. The picture below illustrates this further.
Picture source: https://ib.bioninja.com.au/standard-level/topic-3-genetics/34-inheritance/genetic-diseases.html
As seen in the picture, if the one parent has Huntington’s disease while the other parent does not, 50% of their offspring will also have the disease. On the other hand, if one parent is a carrier of cystic fibrosis and the other parent is not, 50% of their offspring will also have cystic fibrosis. Although carriers are not affected by cystic fibrosis, their offspring has the same outcome as the Huntington’s disease offspring. In other words, both examples have 50% of the offspring being affected by each respective disease. So why is this important?
Scientists have identified an enzyme that is key to understanding Huntington’s disease. Huntington’s disease is caused by a gene mutation for the protein huntingtin. The mutation causes huntingtin to build an extended amino acid tail for glutamine, preventing huntingtin from folding correctly. In turn, neurons inside the brain die; hence Huntington’s disease is characterized as a neurodegenerative disease. While there is no treatment for the disease, current approaches include silencing the huntingtin gene or activating mechanisms to degenerate the protein. A new enzyme discovered by scientists called TBK1 can do both. TBK1 is a kinase, meaning it adds a phosphate group to the huntingtin protein. Research has indicated that adding this phosphate group can stop huntingtin from aggravating and causing the disease.
Increasing TBK1 levels also over-phosphorylates serine, an amino acid that blocks the inhibition of the huntingtin protein. Additionally, TBK1 signals the cell to get rid of the huntingtin protein before it can be activated, thus lowering the body’s huntingtin levels. These discoveries are promising because it paves the way for possible treatments that can be used to combat the disease in the future. Professor Hilal Lashuel at the Ecole Polytechnique Fédérale de Lausanne (EPFL) states that TBK1 also plays an essential role in other neurodegenerative diseases such as ASL. “Our goal is to find small molecules or drug pathways and to develop these for multiple neurodegenerative diseases,” he says.
Sources:
“Brent Cornell.” BioNinja,
ib.bioninja.com.au/standard-level/topic-3-genetics/34-inheritance/genetic-diseases.html.
Ecole Polytechnique Fédérale de Lausanne. "Discovery shows promise for treating
Huntington's Disease." ScienceDaily. ScienceDaily, 5 August 2020.
<www.sciencedaily.com/releases/2020/08/200805110117.htm>.
“Huntington's Disease.” Healthdirect, Healthdirect Australia,
www.healthdirect.gov.au/huntingtons-disease.
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Laurent Mouchiroud, Johan Auwerx, Christian Landles, Gillian P Bates, Malvindar K
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