A Doctor, a Mutation and a Potential Cure for HIV/AIDS

[Bluebear]

Aas with many potential cures, it appears to have been discovered strictly by accident:

The startling case of an AIDS patient who underwent a bone marrow transplant to treat leukemia is stirring new hope that gene-therapy strategies on the far edges of AIDS research might someday cure the disease.

The patient, a 42-year-old American living in Berlin, is still recovering from his leukemia therapy, but he appears to have won his battle with AIDS. Doctors have not been able to detect the virus in his blood for more than 600 days, despite his having ceased all conventional AIDS medication. Normally when a patient stops taking AIDS drugs, the virus stampedes through the body within weeks, or days. "I was very surprised," said the doctor, Gero Hütter.

The breakthrough appears to be that Dr. Hütter, a soft-spoken hematologist who isn't an AIDS specialist, deliberately replaced the patient's bone marrow cells with those from a donor who has a naturally occurring genetic mutation that renders his cells immune to almost all strains of HIV, the virus that causes AIDS.

The development suggests a potential new therapeutic avenue and comes as the search for a cure has adopted new urgency. Many fear that current AIDS drugs aren't sustainable. Known as antiretrovirals, the medications prevent the virus from replicating but must be taken every day for life and are expensive for poor countries where the disease runs rampant. Last year, AIDS killed two million people; 2.7 million more contracted the virus, so treatment costs will keep ballooning.

While cautioning that the Berlin case could be a fluke, David Baltimore, who won a Nobel prize for his research on tumor viruses, deemed it "a very good sign" and a virtual "proof of principle" for gene-therapy approaches. Dr. Baltimore and his colleague, University of California at Los Angeles researcher Irvin Chen, have developed a gene therapy strategy against HIV that works in a similar way to the Berlin case. Drs. Baltimore and Chen have formed a private company to develop the therapy.

http://online.wsj.com/article/SB122602394113507555.html?mod=special_page_campaign2008_mostpop#articleTabs_comments

[Lyric]

1. This is fantastic, and it doesn't surprise me either.

My Mom had acute myelogenous leukemia eight years ago--a cancer in which the 5 year survival rate for adults is only 19.8%. She underwent heavy chemotherapy to completely destroy her own bone marrow, then had both a bone marrow and a stem cell transplant. The cancer went away, and after eight years, has never come back. But more importantly is what happened in regard to her heart.

Before she developed leukemia, Mom had already had three heart attacks. Her heart was severely damaged, and her docs didn't think she'd be a good candidate for a coronary bypass because she has lung problems, and because her coronary arteries are genetically tinier and more narrow than usual. Three years after the bone marrow/stem cell transplant, her docs were doing an angiogram to check out the condition of her heart when they found something shocking and amazing: her heart was growing NEW coronary arteries around the blockage, all by itself, and appeared to be slowly healing the damage done by the previous MI's.

I can totally see how destroying "ineffective" bone marrow and replacing it with bone marrow that can produce AIDS-fighting white blood cells could be a potential cure. I pray to whatever higher powers might exist that this pans out--and if it does, I will cry myself to sleep for years in relief, and in grief for the ones I have loved who didn't make it.

:cry:

[northernlights]

10. just a correction on the "AIDS-fighting white blood cells"

The white cells of HIV-immune people do not fight AIDS or the HIV virus.

HIV gains entry by binding to 2 receptor proteins in the membranes of the white cells (specifically CD4 t-lymphocytes). People who are naturally immune have a genetic mutation that prevents the production of one of the 2 receptor proteins, so their cell membranes lack that protein. As a result, the virus is unable to bind to or penetrate the white cells, and therefore is unable to infect and reproduce.

Since lymphocytes are made by red bone marrow, it makes sense that marrow transplanted by HIV-immune donors may make lymphocytes lacking one of the binding proteins. Marrow transplant is already used to treat other, innate immune deficiencies.

However there are still many practical hurdles to overcome. Organ transplantation depends on close matches between donor and recipient; 30% of bone marrow transplants are from family members. But the families of HIV patients are not likely to carry the genetic mutation. Also, there are probably a huge number of HIV patients relative to the number of naturally immune potential donors. Also transplants don't always work. 15% of the time, the patient dies; other times the transplant fails and they need a 2nd transplant.

[Lyric]

11. I wonder if there is a way for genetic engineers

to use a virus as a "delivery" system to insert that particular genetic mutation into the DNA of people with HIV infections. Does the body function normally otherwise, even without that second receptor protein?

I am also curious as to whether or not that particular mutation is heritable, and if so, in what manner--Mendelian, or incomplete dominance.

I had never heard an explanation of exactly how the bodies of immune people manage to fight the virus, so thank you for that. :)

[1monster]

14. My father, who never had chemo or a bone marrow transplant also was growing new arteries

around two blockages that he had. He is 81 years old.

Doctors watched the growth of the new arteries for several months, but decided to put in two stents because the blockages were growing faster than the new arteries.

I'm not sure how common this phenomenon is, but it is not so uncommon as to be unheard of. Genetics probably have more to do with the growth of new arteries than chemo or bone marrow transplants. (Which could be good news for you. :))

[Ysabel]

2. k and r...

thanks / good article / very promising...

about 25 yrs. ago i read a very in depth article in scientific american concerning the percentage of people who are immune and i believed that research in that area would be very helpful towards finding a cure...

- a member of my family has AIDS / he has had it for a very long time (he is fortunately doing well / however his partner died from it in 1983)...

[ColbertWatcher]

3. Yay science! k+r, n/t

[crickets]

4. Wonderful! Fingers crossed. K&R

[pleah]

5. K&R! Science rules! n/t

[rainbow4321]

6. K&R!

[rasputin1952]

7. About 2 weeks ago, I read where a Russian/Romanian team...

made a breakthrough in drug therapy as well. The drug apparently blocks the receptors, but it will take several years for testing to be complete.

Science mmarches on!

[nichomachus]

8. They've been studying the role of bone marrow for a long time

I'd wait a while before breaking out the champagne over this one case. It could be a fluke. You'd need to see it replicated and then study the long-term effects. HIV is an extremely tricky virus.

[Recursion]

13. There were some marrow replacement successes in the 1990's too

In that case the problem was the treatment has a lower 10-year survival rate than AIDS. This one may improve things.

[SalmonChantedEvening]

9. K&R with hope. n/t

[LastDemocratInSC]

12. This is a difficult and dangerous course of treatment

It's important to prevent "graft versus host disease" in which the body rejects the bone marrow cells. The first step to prevent this is to expose the entire body to intense radiation, usually from Cobalt-60, to kill the existing bone marrow (and other cells which are 'collateral damage'). The patient is exposed from head to toe with radiation that is usually very carefully targeted during radiation therapy for cancer ... the radiation from Cobalt is very damaging. This step presents many of its own risks. If this step succeeds, meaning that a terrible infection doesn't start while the immune system is suppressed by the whole-body radiation, then the marrow transplant might have a chance to work. This is a classic case of the the cure being almost as bad as the disease.