Thursday, December 16, 2010

HIV cure with Stem cells? The Berlin Patient

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To make clear from the start: what this study reports is (at this point) a Proof of Concept.

A number of factors need to be accounted for.

This was no simple: "here, drink this solution containing stem cells and you will be HIV free!"

The case of the Berlin Patient, an american citizen living in Berlin, was first reported in 2008 and now, 3 years down the line, there was a follow up of the case. This is still an amazing achievement in one particular patient. 

The abstract from the paper (Allers et al; doi:10.1182/blood-2010-09-309591) (my comments in italic):

HIV entry into CD4+ cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. 
(CD4 is a primary receptor used by HIV-1 to gain entry into host T cells; T cells play a major role in cellular immunity, being most effective in removing virus-infected cells, but also participates in defending against fungiprotozoanscancers, and intracellular bacteria. It also plays a major role in transplant rejection)  

We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5Δ32/Δ32 stem cells.
(The patient stopped taking drugs for HIV after being transplanted with Bone Marrow Stem cells with mutation in CCR5, these cells are naturally resistant to infection by R5 HIV strains)

However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution.
 (Therefore the results were not expected) 

In the present study, we demonstrate successful reconstitution of CD4+ T cells at the systemic level (i.e. in the blood stream) as well as in the gut mucosal immune system following CCR5Δ32/Δ32 stem cell transplantation, while the patient remains without any sign of HIV infection.
(one of problems of radiotherapy is that the immune system gets compromised, killing most, if not all, bone marrow stem cells, therefore impeding the production of new T cells. After transplantation "new bone marrow" the body is able to produce T cells again)
 
This was observed although recovered CD4+ T cells contain a high proportion of activated memory CD4+ T cells, i.e. the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.

So this particular patient apart from being HIV infected, he also suffered from leukemia (blood cancer). He had received a 1st transplant of Bone Marrow stem cells and some time later the cancer came back (relapsed). He received a second transplant from a donor with that rare genetic mutation that conferred resistance to HIV (CCR5Δ32/Δ32). At this time he stopped antiretroviral therapy (ART) for HIV. Three year later (i.e. now) he seems to be cancer and HIV free.

The good things:
1) It shows that there is a way of erradicating (as it seems) the HIV infection. It shows that scientists are on the right path (but it is probably not the only one)

The not so good things:
1) Transplantation is a major thing (30% of patients die)
2) does it really pay to undergo transplantation when the HIV therapies available today can provide HIV patients with a life span up to 70-80 years?
3) About one in 100 Caucasian people have the mutation (CCR5Δ32/Δ32), finding a compatible match will extremely difficult.
4) (to my understanding) The mutation is only resistant to a strain of HIV.
5) Three years is still a very short time to make this a definite proof.

This is a life-threatening treatment as it is and the next step is to devise strategies to reduce the risks of such therapy. Companies and  Research groups in the US are trying to manipulate the patients own stem cells to try therapies that are similar to the one given to the Berlin patient. At least with would reduced the host-graft rejection that tends to happen in normal transplantations.

Still very interesting (and IMHO much more the the As-Bacteria story...)

14 comments:

brballoon said...

Muito interessante, de facto.
Embora também ache que numa avaliação do risco-benefício do transplante versus toma de anti-HIVs orais, estes últimos "ganham".

Eu também fiquei com a impressão que as células só são resistentes a uma estirpe de HIV. Resta saber que prevalência tem essa estirpe no Mundo?

THank you for the share!

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