Archive for March, 2011


Targeted gene therapy for HIV/AIDS

Saturday, 5 March, 2011

Some scientists (I still have no idea who) reported treating six patients with ex vivo gene therapy for the treatment of HIV/AIDS. Researchers used zinc finger nucleases to edit out the CCR5 gene from CD4-positive T-cells. Because HIV (or, most strains of it) uses the CCR5 protein to infect CD4+ T-cells, this essentially creates white blood cells that are immune to HIV. People with a deletion in their CCR5 gene (5-14% of Europeans have at least one such deletion, the CCR5-Δ32 allele) are essentially immune to AIDS (though they can sometimes get asymptomatic HIV infections).

All six patients showed some immune recovery, with five showing up to 6% of their cells modified, so that’s progress, I guess. Side effects were just a couple days of flu-like symptoms. In this study, the cells were removed from the patient and edited outside the body, probably because the ridiculous safety standards required for gene therapy that I recently blogged about pretty much rule out modifying the patient’s genes directly (i.e. in vivo). And I suppose the zinc finger nucleases probably aren’t as efficient as using a virus, so it wouldn’t really work in vivo just yet.

This is, however, the first time that human gene therapy has actually deleted a gene, rather than adding one. Pretty soon, addition, deletion, modification, replacement…it’ll all be possible.

Some scientists are, I think sensibly (with just 6% of cells modified), trying to avoid the work being overhyped as a ‘cure’. For example, Dr Michael Kolber, professor of medicine at the University of Miami:

“[This study] was a proof-of-principle that they could go in and do this. They demonstrated that the [genetically engineered] cells stayed in the patients, but the patients were not cured”

Of course this gets reported as:

Experts are reacting with cautious optimism…but they say the jury is out on whether the technique might ever spell an end to AIDS.

No, the jury isn’t out on whether the technique might ever work, just whether it has worked. It’s obvious beyond a reasonable doubt that gene therapy could provide both immunity and cures for HIV infections. And I’d say it’s obvious that gene therapy could cure all disease (and I’m not overhyping, just don’t expect these cures tomorrow and without side-effects during their early stages of development).


Gene therapy: my choice method of suicide

Wednesday, 2 March, 2011

We should be modifying our genes, right now. It’s estimated that over 3000 diseases can be pinned down to a specific gene. To cure these diseases, it’s obvious we need to modify our genes. Furthermore, the most common diseases of the Western world – cardiovascular diseases, neuropsychiatric diseases and cancer – involve interactions between genes and the environment. We are severely lacking ability to treat these conditions (especially cancer), so we need to expand into genetic modification.  In fact, I’d go so far as to say that all causes of death, perhaps with the exception of sudden fatal injuries, could be dramatically reduced if only we were modifying our genes. Essentially all medical problems could theoretically be solved by modifying our genes to treat or cure disease – termed gene therapy – and modifying our genes to make us healthier than is currently possible – designated as genetic enhancement.

Gene therapy – the insertion, removal or modification of genes to treat or cure disease – has already saved lives. The blind have been made to see1,2,  fatal brain diseases have been cured3, hemophilia treated4, metastisising tumours have been stopped in their tracks 5, children and adults have had compromised immune systems restored to normal6, 7. The list should go on and on, but it doesn’t. Why?

Because gene therapy, as promising as it is, is held back in the very nations where we should be seeing more great advances in gene therapy. The technique is drastically underfunded and governments have harshly regulated it. It therefore requires more research to get approval for clinical studies, and the funding for such research simply isn’t available. For that reason, biotech industries and scientists have left the field.  There was, essentially, a gene therapy ‘recession’ 8.

Furthermore, inheritable gene therapy, which could prevent the need for future generations to seek gene therapy for their disease (and genetic conditions cause a large proportion of miscarriages and infant deaths), is prohibited in many countries, including Australia, Canada, Germany, India, South Korea and the United Kingdom 9. Why has such a promising medical treatment been held back?

Primarily, the hold up has been due to slanderously bad press and largely unfounded concerns about dangerous side-effects. Gene therapy killed teenager Jesse Gelsinger in 1999 and caused leukemia in several children treated for severe combined immunodeficiency (SCID). But the 17 other patients treated before Gelsinger did not show any severe symptoms as a result of the gene therapy (though one did show mild symptoms), and I believe they’re all doing fine today, and of the 9 children treated in the French SCID trial, only 1 died (3 others developed cancer but were successfully treated for that) and 7 of the 8 surviving children showed at least partial improvements in their immune function.  So even in the gene therapy “horror stories”, the treatment was 94% and 77%  effective. The fact is undeniable: gene therapy has always cured (or treated) the majority of patients who received it.

It makes no sense to expect gene therapy would have no side effects and it makes no sense to stop research into it due to those side effects. Doing nothing is not necessarily safe. We don’t know what the future will bring, whether gene therapy will be great or a disaster, so we don’t know which is the safer path: gene therapy or no gene therapy. All we know is that gene therapy has cured people and was more likely to cure you than kill you.

So imagine, for a moment, that you were diagnosed with one of the many rare genetic conditions that affect so many of the population. Gene therapy is your only option, there is no other treatment for this condition. You will die, very soon, and very painfully, without gene therapy. Gene therapy could not only cure your condition, but prevent your children from being born with the same condition. Would you consent to an experimental and high-risk treatment for that, even if it could kill you?

If you’re like me, you would not only consent to the treatment, but you’d campaign for the right to get the treatment even if the government wouldn’t approve it. After all, your choice is either certain painful death, or a possible cure that might cause another type of painful death.

And once scientists work out how to effectively replace genes for the most terrible of genetic conditions, they will be able to translate that knowledge into gene therapy for other conditions. First non-lethal but incurable diseases, and then even as a better treatment for otherwise treatable diseases. And then, genes could be inserted that prevent diseases like cancer, heart attack and neurological conditions. Ultimately, inserted genes could prevent all infections, improve healing from accidents, give faster reflexes and concentration to make accidents less likely and prevent age-related disease.

We need gene therapy. We need it as soon as possible. I don’t care if it kills me: if I’m going to die, I intend to die from gene therapy. I want my death to be an attempt to cling to life. Gene therapy is my choice method of suicide.