Context: The UK scientists have conducted the first-ever trial of a new drug for Alzheimer's disease that is able to safely and successfully lower levels of the harmful tau protein known to cause the disease.
Major Highlights:
- The trial represents the first time that a "gene silencing" approach has been taken in dementia and Alzheimer's disease.
- The approach uses a drug called BIIB080 (IONIS-MAPTRx) to "silence" the gene coding for the tau protein -- known as the MAPT (microtubule-associated protein tau) gene. This prevents the gene from being translated into the protein, lowers the production of that protein and alters the course of the disease.
Significance:
- The results demonstrate that the tau protein can be successfully targeted by gene-silencing drug to slow -- or possibly even reverse -- Alzheimer's disease, and other diseases caused by tau accumulation in the future.
Alzheimer's disease:
- Alzheimer's disease is a progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die. It is the most common cause of dementia — a continuous decline in thinking, behavioural and social skills that affect a person's ability to function independently.
- Causes: The disease is thought to be caused by the abnormal build-up of proteins in and around brain cells.
- One of the proteins involved is called amyloid, deposits of which form plaques around brain cells.
- The other protein is called tau, deposits of which form tangles within brain cells.
- Symptoms: Early signs include forgetting recent events/conversations. Later, the person will develop severe memory impairment and lose the ability to carry out everyday tasks. In the advanced stages, complications from severe loss of brain function result in death.
- Treatment: Currently, there is no cure for Alzheimer's disease, but certain medications can temporarily slow the worsening of dementia symptoms.
Gene silencing:
- Gene silencing refers to the process of turning off or decreasing the expression of a gene. It can occur naturally in cells or it can be induced through artificial means. The popular processes are:
1. RNA interference:
- RNA interference (RNAi) is a natural gene silencing process that occurs in cells as a way to regulate gene expression. It involves the use of small RNA molecules to target and degrade specific messenger RNA (mRNA) molecules, thereby decreasing or turning off the expression of the targeted gene.
- However, scientists have also developed artificial methods of inducing RNAi in cells, such as by introducing synthetic small interfering RNAs (siRNAs) that can specifically target and degrade mRNA molecules. By interfering with the mRNA, the gene expression can be decreased or turned off, thereby silencing the gene.
2. CRISPR-Cas9:
- CRISPR-Cas9 is a gene editing tool that allows researchers to selectively modify DNA sequences in cells. It works by using a guide RNA molecule to target a specific DNA sequence and then using the Cas9 enzyme to cut the DNA at that location. This can be used to either introduce specific changes to the DNA sequence or to disrupt the function of a specific gene, leading to gene silencing.