How gene therapy could cure brain diseases

Nature’s neurology journal has a freely available article on a technique that interferes with the translation of genetic information into proteins that may help prevent inherited brain diseases.

DNA has two main functions. The ‘template function’ of DNA is to pass on genes through generations and allow different traits to be inherited.

The ‘transcriptional function’ of DNA is to allow these genes to be expressed at appropriate times and places (and not expressed at others) to allow the cell to do its work.

‘Expression’ just means ‘turned into a protein’ and genes are just blueprints for proteins.

The blueprint gets turned into a protein by messenger RNA, which ‘reads off’ the information, then moves away to assemble the protein from a store of amino acid component parts.

As different cells in the body have different functions, and individual cells need to behave differently depending on what’s happening, different proteins need to be created at different times.

Disorders like Huntington’s disease result from genes that cause damaging proteins to be formed. These lead to the malfunction and death of brain areas that, in turn, leads to cognitive problems, movement difficulties, mental illness and eventual death.

Using a technique called RNA interference, researchers have found they can selectively interfere with the process where messenger RNA assembles proteins from the DNA’s genetic information.

Essentially, small chunks of gene-specific RNA are introduced into the cell, these find the messenger RNA and destroy the information before it gets turned into a protein.

In other words, it prevents specific genes from being turned into proteins.

This has caused a great deal of excitement because it could lead to treatments for disorders like Huntingdon’s by simply ‘silencing’ the rogue Huntingdon’s gene.

While you might have a rogue gene, RNA interference could essentially gag it, meaning it would never have a knock-on effect in the brain.

This has been demonstrated in very limited lab tests, and the Nature article examines the prospects for it being developed into a widespread treatment.

There are still some difficulties to overcome, however. One of which is how to get the interfering RNA into the right cells in the brain, a difficulty with many treatments owing to the filtering effect of the blood-brain barrier.

Another is how to make sure that the technique affects only the disease process. Researchers talk about proteins being involved in ‘chemical cascades’, meaning that they are involved in huge and complex mechanisms in the body.

It’s hard to predict exactly what effect silencing a gene will have, and whether your technique for doing so will also interfere with some other processes that use some of the same mechanisms, some of which we probably don’t even know about at the present.

RNA interference is still an experimental process, but it holds great potential for treating inherited brain diseases. The Nature article is a fantastic guide to the cutting edge of the science in this area.

Link to Nature Clinical Practice Neurology article on RNA interference.
Link to plain language guide to its use in Huntington’s.
Link to Wikipedia page on RNA interference.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: