Question of the Week

Can gene therapy treat depression?

Wed, 17th Apr 2013

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Question

Wilson da Vinci asked:

I have suffered from depression for many years. I have tried every medicine on the market but nothing realy helped. I heard about gene therapy for depression and my question is: When will that treatment will be available for a patient like me? Do you know anything about who will start to do gene therapy for depression first?

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There are a number of challenges to be overcome before we can have an effective genetic therapy for depression:

There are arguments about whether we have discovered a gene that cause susceptibility to depression.

If/when such genes are discovered, it is likely that there will be a number of interacting gene variants, each making a small contribution in the entire population - and probably interacting with environmental factors such as life experiences. Finding all of the contributors will be a challenge.

There is no guarantee that the DNA code itself is the culprit, but there may be epigenetic markers that are contributing to the symptoms. But progress is being made in reading epigenetic markers too.

Assuming that relevant gene(s) are discovered, there is the challenge of identifying which cells in the body are expressing the wrong gene, and obtaining an undesirable outcome. Once this population of cells are discovered, we must determine how we can reach these cells with the gene therapy.

Another question is whether changing the gene expression now can rewire brain connections which have developed over many years, and what percentage of affected cells must be modified to make a significant difference.

And then we must determine whether you have one of the known genes for depression. These days, this can be done fairly economically with a gene chip. In a decade or so, the price of DNA sequencing is likely to drop sufficiently that everyone could have their whole genome sequenced, which allows screening for any new genes discovered in the future, without another test.

Some types of gene therapy have significant risks, such as the possibility of causing cancer. Researchers are looking for safer ways to implement gene therapy, but until proven-safe techniques are discovered, gene therapy will be restricted to life-threatening diseases like cystic fibrosis.

I don't want to make this look hopeless - we don't necessarily need to implement gene therapy to benefit from our modern genetic discoveries. Once a genetic problem is discovered, pharmaceutical companies can develop medications which provide or imitate the missing protein, or address a related genetic pathway which will achieve the same effect.

Pharmaceutical companies have a significant incentive to develop medications which must be taken daily for a lifetime, especially if there is a large segment of the population who will benefit.
Before developing a new medication, they will screen already-approved medications to see if they impact this newly identified genetic pathway - this provides a much faster and cheaper market entry, since the safety tests have already been done, and there is a large body of evidence from the previous application about safe dosages, possible side-effects, etc.

So I guess the conclusion is - some genetic-based therapies should eventually become available, but it might still take a while. evan_au, Sat, 13th Apr 2013

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