‘HIV could be cured by genetically editing stem cells’
‘HIV could be cured by genetically editing stem cells’
- Written by Chukwuma Muanya, with agency reports
RESEARCHERS say Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) could be cured by genetically editing stem cells.
United States (U.S.) scientists say they have already demonstrated that it is possible to alter the genetic material of some stem cells. This in turn provides HIV resistance, they report.
The researchers, at the University of California, San Francisco, have found a way of removing one DNA sequence and replacing it with a different one, a technique known as ‘genome editing’, New Scientist reports.
In this case, they replaced it with a rare DNA sequence that gives some people natural HIV resistance.
This DNA sequence comes from people who have two copies of a mutation in a gene linked to the protein CCR5.
HIV attaches to CCR5 when attempting to invade a person’s white blood cells. In people with the gene mutation, HIV is unable to attach to this protein meaning the person cannot become HIV positive. Only about one per cent of European people have two copies of the gene mutation.
The idea behind the research was the treatment of the so-called Berlin patient. Timothy Ray Brown was ‘cured’ of HIV after receiving a bone marrow transplant from a person who was resistant to the virus.
This is not a practical way of curing patients as there are hardly any HIV-resistant bone marrow donors. So, the University of California researchers attempted to achieve the same thing but without a bone marrow donor.
They say it is quite easy to make the necessary stem cells from a patient’s own cells and that these stem cells – which can be used to create white blood cells – can then be genetically edited to offer HIV-resistance.
These edited stem cells could then be transplanted into patients causing them to develop HIV-resistance.
It is hoped this technique could eventually offer a personalised equivalent of the treatment Mr Brown received.
The researchers accept, however, that they are a long way from being able to use the technique in practice.
To date, they have only got so far as to prove it is possible to edit the genome to produce white blood cells that are HIV-resistant.
Also, new global clinical trial aims to replicate mysterious ‘Mississippi baby’ success. When an infant born with HIV was reportedly ‘cured’ of the disease it seemed too good to be true.
The success, detailed by researchers in March 2013 and later published in The New England Journal of Medicine, ignited hope that other babies could benefit from the same aggressive drug regimen that the infant received.
Through a series of rare circumstances the so-called ‘Mississippi baby’ began standard HIV treatment 30 hours after birth, but the potent drug cocktail regimen was abruptly halted when the child was 18 months old.
Surprisingly, even after treatment stopped the child’s blood plasma continued to show no signs of the virus. The baby is now more than three years old and remains seemingly disease-free. But exactly how that child bested the virus that causes AIDS remains a mystery.
That’s where the US National Institutes of Health comes in. This month the NIH expects to launch a global study that will attempt to replicate the Mississippi baby results. Researchers plan to identify 54 HIV-positive infants and treat them with standard antiretroviral drugs, beginning treatment within 48 hours of birth. The team plans to enroll HIV-positive infants across 17 hospitals and clinics in the United States and 11 other countries, including Haiti, India, Malawi, South Africa and Thailand.
After patients receive the aggressive drug course for an extended period (likely the first two years of life), researchers will discontinue the therapy if they cannot find any virus in the child’s blood. The babies will then be carefully monitored to see if the virus boomerangs. “Any child enrolled will have the potential to be followed for five years,” says Ellen Gould Chadwick, one of the investigators leading the clinical trial and a professor of paediatrics and infectious diseases at Northwestern University Feinberg School of Medicine in Chicago. If the infection creeps back, the child’s drug treatment will resume.
“To the best of our knowledge there is no virus in the Mississippi baby, so we consider the baby cured. Now you have a cured case, but the n equals 1. That is encouraging, but in medicine you have to go beyond that,” says Anthony Fauci, executive director of the US National Institute for Allergy and Infectious Diseases.
Managing HIV can turn into a lifelong high-stakes game of microbial hide-and-seek. The standard battery of anti-AIDS medications may be successful at suppressing HIV but they do not eliminate it from the body. The virus hibernates in reservoirs of long-lived, resting memory CD4+ T cells. These cellular reservoirs can withstand antiretroviral drugs even when a patient has been on medication for years. If doctors could stop the infection before those reservoirs form - with early, aggressive treatment - then perhaps drugs could wipe out the infection entirely.
To date, researchers remain unsure if the Mississippi baby and other HIV-positive infants are born devoid of such viral reservoirs - which would imply that early treatment could block their formation - or, perhaps, infected infants have viral reservoirs that are somehow more amenable to being eliminated or eradicated than those in adults. This clinical trial will hopefully provide some initial answers to that question. “This is going to be a very important study,” Fauci says. “This would be a huge advance- that you could actually cure babies.”
Enrolled infants will receive a three-drug regimen that will be augmented with a fourth drug weeks after birth. Once the treatment helps the child tamp down the levels of virus for at least three months, the infant will receive just three drugs until doctors halt the treatment entirely. An institutional review board will also have to approve the trial at each study site. But, even with the aggressive drug-course protocol, Fauci says the “benefit of the therapy overwhelmingly outweighs the risk of toxicity”, pointing to instances where infants already received treatment when they were under one or two years old.
This study also aims to include two separate groups: babies, like the Mississippi baby, that will be fed on formula; and babies that breast-feed from mothers who are also receiving antiretroviral treatment. Infants in many settings depend on a mother’s milk for protein, especially when there may not be reliable supplies of safe water and affordable formula. The investigators designed their research this way to reflect that reality. The NIH is allocating $5.2 million for the study.
One of the brightest spots in the global effort to combat HIV has been reducing mother-to-child transmission. If an HIV-positive mother receives the standard potent cocktail of drugs during pregnancy, the infant is born disease-free more than 99% of the time; more than half of HIV-positive mothers reportedly get that treatment. Yet far too often expectant mothers may not know their disease status or, for a variety of reasons, do not access prenatal care or HIV medications. In the US, where most HIV-positive mothers receive anti-AIDS medications during pregnancy, an estimated 127 babies were born with the disease in 2011. A success with this clinical trial would likely lead to an overhaul in how physicians typically approach HIV treatment in infants, and reduce the number of children living with the disease.
Even when an HIV-positive mother does not receive treatment during pregnancy her child may still be born disease-free. Transmission rates from mother to child range from 15 to 45 p, so investigators will have to enroll many infants in their study before confirming HIV infection.
It was a terse report 33 years ago this month that catapulted the virus that causes AIDS into our public consciousness. That first mention was tucked into the weekly newsletter from the US Centers for Disease Control. It detailed a rare parasitic lung infection among “five young men, all active homosexuals”.
icons on the left to see existing comments.
0 General Document comments
0 Sentence and Paragraph comments
0 Image and Video comments
People with a mutation in this protein are HIV resistant.
New Conversation
Hide Full Comment
Only European people are immune. Crazy.
New Conversation
Hide Full Comment
In order for this to work we would need:
1. many people (from the 1% of Europeans) to donate bone marrow
2. to find a match between the infected person and the donor
New Conversation
Hide Full Comment
Is this the “playing god” part that people are afraid of?
New Conversation
Hide Full Comment
This would be costly and specific to each individual patient, meaning that its not practical for most people.
New Conversation
Hide Full Comment
Only 127 babies born with HIV in an entire year! Crazy!!! But, how do we make this accessible in other parts of the world!
If we could stop transmission than eventually the virus would have no host and would die.
New Conversation
Hide Full Comment
General Document Comments 0
