My alarm bells get deafeningly loud whenever I see the word 鈥渃ure鈥� associated with AIDS, cancer and other serious conditions that are almost, by definition, incurable.
And so it was this morning on reading that a haematologist in Berlin, that he had cured a 42-year-old American patient of AIDS by giving him a bone-marrow transplant 鈥� a seemingly illogical approach to tackling the disease.
His was made possible by studies in the late 1990s revealing that some people were resistant to HIV.
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It turned out that in these people, the virus can鈥檛 enter and destroy the white blood cells that it infects and destroys in most other people. They owed their resistance to a mutation in the gene which makes the molecular 鈥渄oor handle鈥� by which HIV gains access to cells.
Locked out
Called CCR5, the protein door handle was misshapen in the immune individuals, locking HIV out of their white blood cells. Since the discovery, it has been established that about 1% of Europeans have the same mutation, making them resistant to HIV. To be resistant, they had to inherit the same mutation from both parents.
H眉tter made use of this when treating his patient for leukaemia, which he had developed in addition to AIDS. To treat the leukaemia, H眉tter did the usual thing and sought a bone-marrow donor to replenish the patient鈥檚 blood supply following chemotherapy to kill the existing, cancerous blood cells.
But H眉tter鈥檚 new approach was to get a donor who had the double HIV-resistant CCR5 mutation. This meant that the patient鈥檚 replenished blood system would effectively be resistant to HIV, locking out the virus for good. This is what appears to have happened, and H眉tter declared his patient 鈥渇unctionally cured鈥�.
So has he come up with a technique to save the millions of people worldwide with the HIV virus? Trouble is, compatible donors with the CCR5 mutation are few and far between, restricting practically to zero the chances of repeating the procedure on a large scale.
New hope
The good news, though, is that there are other treatments in the pipeline based on the same principle.
We reported on one earlier this year that uses molecular 鈥渟cissors鈥� called zinc-finger proteins, specifically designed to ruin the CCR5 protein in patients. The approach, developed by a company called in San Diego, worked in mice.
Other teams, such as the one led by Nobel-prizewinner at the California Institute of Technology in Pasadena, are developing a similar approach, using molecules called small interfering RNAs (siRNAs) to sabotage production of CCR5 by white blood cells.
This suggests that the news from Germany is a sound proof of principle, demonstrating that there is hope for treatments that literally lock HIV out in the cold.
Edward Berger, who discovered the link in the late 1990s between CCR5 and HIV at the US National Institutes of Health in Bethesda, Maryland, warns that HIV might yet have a potential sting in its tail. It turns out that there鈥檚 a second 鈥渄oor handle鈥� by which HIV can sometimes gain entry into cells, called CXCR4. 鈥淭here鈥檚 always a concern that if you block CCR5, you favour virus evolution,鈥� he says.
So even if CCR5 is not available, the virus may evolve to get in through the back door, and Berger says it鈥檚 not a question of using transplants or siRNA to knock out our ability to make CXCR4 too. He says that we already know that people can do without CCR5, but mice lacking CXCR4 die as embryos, so knocking out the gene might not be an option if not having it is also lethal to humans.
