Remembering a stem cell pioneer in the fight against HIV/AIDS

Timothy Ray Brown. Photo courtesy Seattle Times

Timothy Ray Brown, a man who was the first person to be cured of HIV, giving hope to millions of people around the world, died at his home in Palm Springs this week. He was just 54 years old.

For years Brown was known simply as “the Berlin patient” because that was where he was living when he made medical history. He was diagnosed with HIV in 1995 and began taking medications to keep the virus under control. He was later also diagnosed with leukemia. He underwent several rounds of treatment for the leukemia, but it kept recurring.

By 2007 Brown’s physician decided the best way to treat the leukemia was with a blood stem cell transplant. But the doctor also wanted to see if using the stem cells from a donor who had a natural immunity to the AIDS virus could help treat Brown’s HIV. While such donors are very rare, the doctor succeeded in finding one whose bone marrow carried the CCR5 gene, a mutation that is believed to provide resistance to HIV. The transplant was a success, putting Brown’s leukemia into remission and eliminating detectable traces of HIV. For the first time in years he was able to stop taking the medications that had helped keep the virus under control.

The procedure quickly garnered world-wide attention. But not everyone was convinced it was real. Some questioned if Brown’s HIV had really been eradicated and speculated that the virus was merely suppressed. But with each passing year, and no signs of the virus recurring, more and more people came to believe it was a cure.

Initially Brown remained in the background, preferring not to be identified. But three years after his transplant he decided he had to come forward and put a face on “the Berlin patient”. In an interview with the website ContagionLive he explained why:

“At some point, I decided I didn’t want to be the only person in the world cured of H.I.V.,” I wanted there to be more. And the way to do that was to show the world who I am and be an advocate for H.I.V.”

He proved to be a powerful advocate, talking at international conferences and serving as living-proof that stem cells could help lead to a cure for HIV.

But while he managed to beat HIV, he could not beat leukemia. He suffered relapses that required another transplant and a difficult recovery. When it returned again this time, there was little physicians could do.

But Timothy Ray Brown did get to see his hope of not being the only patient cured seemingly come true. In September of last year researchers announced they had successfully treated a second person, known as “the London patient” using the same technique that cured Brown.

While it wasn’t the role he would have chosen Brown was a pioneer. His experience showed that a deadly virus could be cured. His courage in not just overcoming the virus but in overcoming his own reluctance to take center stage and becoming a symbol of hope for millions remain and will never die.  

Since Brown’s transplant many other scientists have attempted to replicate the procedure that cured Brown, in the hopes of making it available to many more people.

CIRM has funded three clinical trials targeting HIV, two of which are still active. Dr. Mehrdad Abedi at UC Davis and Dr. John Zaia at City of Hope are both using the patient’s own blood forming stem cells to try and defeat the virus.

If they succeed, some of the credit should go to Timothy Ray Brown, the man who led the way.

One thought on “Remembering a stem cell pioneer in the fight against HIV/AIDS

  1. CCR5 is a chemokine receptor existed on the surface of white blood cells. They are predominantly expressed on T cells, macrophages, dendritic cells, eosinophils and microglia. Most of HIV viruses use chemokine receptors to enter target immunological cells. The envelop glycoprotein structure of HIV-1 consist of external submit Gp120 and transmembrane subunit Gp41. Gp120 is capable to bind to CCR5 and CXCR4. During HIV-1 infection, Gp120 binds to CD4, which is expressed on a target cell to form a heteromeric complex. The complex tend to stimulate the release of a fusogenic peptide causing the viral membrane to fuse with membrane of the target host cell. The binding to CD4 alone can sometime results in Gp120 shedding. Thus, after Gp120 binding to CD4, it is followed by binding to CCR5 for fusion to proceed. CCR5-strain of HIV-1 viruses are prominent species among HIV infected patients. They use CCR5 to spread HIV-1 viruses. In some circumstances, selective pressured may cause HIV viruses to evolve and bind to other co-receptor instead of CCR5. However, resistant viruses may sometime persisted in using CCR5: either bound to alternative domains of CCR5 or another receptor with high affinity. Therefore, lacking of CCR5 gene does not make one immune to the virus. In other occasion, virus still can invade host cell by assessing to CD4, even without the available of two co-receptors. If Gp41 goes through alteration that resulted virus become independent of CD4 and without the need of CDC5 and CXCR4 as a doorway.

    Evidence showed that, certain population have inherited of Delta 32 mutation in CCR5 gene. The homozygous carriers of mutation are resistant to M-tropic strains of HIV-1 infection. Scientific evidence supported that high density of CCR5 in peripheral blood CD4-T lymphocytes has strong correlation with high virus load in HIV-1 infected patients. Therefore, CCR5 density is a key factor to determine cell infectability and in vivo viruses production.

    The donor stem cells with Delta 32 CCR5 deletion provides an effective treatment can be used for transplantation into HIV infected patient. In some circumstances, donor stem cells with very low density of CCR5 can also be considered as other alternative of choice for treatment. In addition, antisense oligonucleotide therapy to suppress the functioning of CCR5 can be considered as another choice of treatment for HIV infected patient.

Leave a Reply to Tey Hoon Boon Cancel reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.