Gene therapy

What are genes and what is gene therapy?

A gene is a short piece of DNA which carries our unique genetic information and so determines the physical and mental traits we inherit from our parents. We each have around 23,000 genes and these provide the instructions required for the formation of proteins which produce our cells, tissue and organs.

Genes also play a part in how likely we are to develop a particular illness or condition. Sometimes the genes we inherit are defective – which can lead to a wide range of disorders – or we may inherit the correct genetic information but, as a natural part of the ageing process (or perhaps as a result of environmental factors) the proteins that are coded by the genes may deviate from normal, resulting in illness or disease.

Gene therapy is a relatively new approach to treating or preventing certain conditions using genes instead of medicines or surgery. Gene therapy can take several forms depending on the condition it aims to treat. Most commonly it involves inserting a healthy gene into the cells of a patient with the aim of treating their disease. This works by the new gene instructing the body to build proteins that repair or prevent cells from dying. Other forms of gene therapy involve inserting a copy of a gene to replace a defective one or deactivating a gene that is not functioning properly.

Scientists believe that gene therapy may be effective both for conditions caused by defective genes and for disorders that have an unknown genetic cause or are only partially caused by defective genes, as is the case with Parkinson’s. This they hope will either halt or even reverse the progression of the condition or bring about a cure.

Gene therapy and Parkinson's

Although it is widely agreed that Parkinson’s is not usually inherited through the genes our parents pass on, researchers believe that gene therapy will one day be able to prevent the death of dopamine-producing cells in the brain and help to revitalise dying cells in the early stages of the disease. This is important as current treatments tend to become less effective over time and only control symptoms – they do not slow or halt the progression of Parkinson’s. Gene therapy has the potential to alter the way neurons (nerve cells) in the brain work.

The aim of current research is to be able to deliver specific genes directly into neurons in the affected area of the brain. The three types of gene therapy being researched at present are: 

  1. Proteins that increase levels of dopamine production in the brain - researchers hope that gene therapy will instruct brain cells to produce more dopamine rather than rely on medications such as levodopa or dopamine agonists to increase dopamine production. If more normal levels of dopamine can be achieved then symptoms should be reduced.
  2. Restoring nerve cell activity in the brain - in Parkinson’s the nerve cells in the basal ganglia area of the brain may become overactive.  This part of the brain helps to control movement so any changes in this region will effect on your movement. This over-activity can be lessened by a chemical produced in the brain called GABA.

In this type of therapy, a gene can be inserted to instruct the cells in the basal ganglia to make GABA. This in turn may reduce the over-activity of the nerve cells in this part of the brain.

  1. Growth factors – growth factors can help protect neurons from further damage and also promote their rejuvenation and survival. Although initial growth factor trial results were promising, analysis of the data did not provide statistically significant effects. A new trial is ongoing with improved viral vectors and delivery systems. 

How can beneficial genes be delivered into the brain?

Gene therapy generally uses a carrier molecule, called a vector, to deliver the therapeutic gene to the target cells. Currently, a number of viruses that have been genetically modified to carry DNA are most commonly used as carriers, although other methods are also being researched. Before introducing such viruses, scientists must ensure that their ability to cause infection and travel around the body is removed, ensuring that they work safely and remain within the target area.

In the case of Parkinson’s, researchers inject a viral vector – often the adeno-associated virus and lentivirus – into the target area of the brain. The vector passes its genetic material to the cells so that the therapeutic gene can work either by protecting neurons from further degeneration or by promoting the production of dopamine in the brain. It is important to stress that these viruses are engineered before injection so that they no longer retain the capacity to cause disease or replicate, so each particle can only infect one cell and they then disappear. The novel gene is, however, expressed for a very long time, probably for the lifetime of the neuron.

Who might be useful for gene therapy and are there any risks?

Researchers believe that gene therapy will be useful for a number of people with Parkinson’s, irrespective of whether their condition has been genetically caused. However, as with most treatments, it won’t be suitable for everyone. As part of the clinical trial process scientists will establish who will suit this treatment and those for whom it is not recommended.

As with all treatments, there are some risks. It is thought that there may be side effects within the central nervous system that relate to long-term exposure to therapeutic genes at high levels or there may be an immune response to the treatment. However, this is still under research.

When will gene therapy be available as a treatment?

Gene therapy is still in the early stages of clinical development and is therefore not yet a treatment option, although there are several clinical trials taking place that involve a limited number of people with Parkinson's.

Research is gathering pace and there is much optimism among clinical scientists. A lot of progress has been made and results so far suggest that it should be possible to overcome the various challenges encountered. However, further research and wider clinical trials are, of course, required to demonstrate consistently safe and effective results before this type of treatment can be more widely used.

Key aspects researchers are addressing are that:

  • DNA introduced into cells remains active for a long period, which means that treatment does not need to be repeated frequently.
  • It is possible to regulate the amount of therapeutic material that is present at any time so that the best results can be achieved.
  • Viruses introduced are safe and do not induce an immune reaction.
  • The treatment itself does not induce unexpected detrimental effects due to the ability of inserted therapeutic genes to alter things that were not intended to be changed.
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