Monthly Archives: July 2012

Two more men with HIV now virus-free.

 Two men unlucky enough to get both HIV and cancer have been seemingly cleared of the virus, raising hope that science may yet find a way to cure for the infection that causes AIDS, 30 years into the epidemic.

The researchers are cautious in declaring the two men cured, but more than two years after receiving bone marrow transplants, HIV can’t be detected anywhere in their bodies. These two new cases are reminiscent of the so-called “Berlin patient,” the only person known to have been cured of infection from the human immunodeficiency virus.

These two cases, presented as a “late-breaker” finding on Thursday at the 19th annual International AIDS Conference in Washington, D.C., are among the reasons that scientists have been speaking so openly at the event about their hopes of finding a cure.

“Everyone knows about this ‘Berlin patient’. We wanted to see if a simpler treatment would do the same thing”, said Dr. Daniel Kuritzkes of Brigham and Women’s Hospital in Boston, who oversaw the study. The widely publicized patient, Timothy Brown, was treated for leukemia with a bone marrow transplant that happened to come from a donor with a genetic mutation that makes immune cells resist HIV infection. The transplant replaced his own infected cells with healthy, AIDS-resistant cells. He is HIV-free five years later.

AIDS patients are susceptible to cancers, but they usually stop taking HIV drugs before receiving cancer treatment. “That allows the virus to come back and it infects their donor cells,” Kuritzkes said.

About 34 million people are infected with HIV, the virus that causes AIDS, globally; 25 million have died from it. While there’s no vaccine, cocktails of powerful antiviral drugs called antiretroviral therapy (ART) can keep the virus suppressed and keep patients healthy. No matter how long patients take ART, however, they are never cured. The virus lurks in the body and comes back if the drugs are stopped. Scientists want to flush out these so-called reservoirs and find a way to kill the virus for good.

Brown, and now these two other men, offer some real hope.

Dr. Timothy Henrich and colleagues at Brigham and Women’s Hospital launched a search about a year ago for HIV patients with leukemia or lymphoma who had received bone marrow stem cell transplants. Bone marrow is the body’s source of immune system cells that HIV infects and it’s a likely place to look for HIV’s reservoirs.

“If you took an HIV patient getting treated for various cancers, you can check the effect on the viral reservoirs of various cancer treatments,” Kuritzkes, who works with Henrich, said. They found the two patients by asking colleagues at Dana-Farber Cancer Institute in Boston which, like Brigham and Women’s, is associated with Harvard Medical School.

Both men had endured multiple rounds of treatment for lymphoma, both had stem cell treatments and both had stayed on their HIV drugs throughout. “They went through the transplants on therapy,” Kuritzkes said.

It turns out that was key.

“We found that immediately before the transplant and after the transplant, HIV DNA was in the cells. As the patients’ cells were replaced by the donor cells, the HIV DNA disappeared,” Kuritzkes said. The donor cells, it appears, killed off and replaced the infected cells. And the HIV drugs protected the donor cells while they did it.

One patient is HIV-free two years later, and the other is seemingly uninfected three-and-a-half years later.

“They still have no detectable HIV DNA in their T-cells,” Kuritzkes said. In fact, doctors can’t find any trace of HIV in their bodies — not in their blood plasma, not when they grow cells in the lab dishes, not by the most sensitive tests.

Can the patients be told they are cured?

“We’re being very careful not to do that,” Kuritzkes said.

For now, both men are staying on AIDS drugs until they can be carefully taken off under experimental conditions. “We are not saying, “You are like the Berlin patient’.”

Although the men are HIV-free, Kuritzkes says it’s been an arduous experience for them. After being diagnosed HIV-positive, one underwent rounds of chemotherapy for Hodgkin’s disease, a kind of lymphoma, before receiving the final bone marrow transplant, called an allogeneic bone marrow transplant. It is not an easy treatment to endure.

The men, one from Boston and one from New York, were not initially told their HIV had seemingly disappeared. When researchers realized news media would cover the report, they were informed.

Neither man is being identified for privacy reasons but one is in his 50s and has been infected since the beginning of the AIDS epidemic in the early 1980s. The other man, in his 20s, was infected at birth.

The findings may not apply to all patients. Both men were a little unusual in that they had a genetic mutation that can make immune cells resistant to infection by HIV. Their new immune cells, however, which came from the donors, are fully susceptible to the virus.

“We’re never really going to be able to do bone marrow transplants in the millions of patients who are infected,” Kuritzkes said. “But if you can stimulate the virus and eliminate those cells, we can protect the remaining cells from being infected.”

Separately, two other studies presented at the conference have scientists optimistic about a cure. In one, a cancer drug called vorinostat flushed out latent HIV from a handful of patients, offering the possibility of killing these latent reservoirs. In another, about 15 French patients who got HIV drugs very early after their infections were able to stop treatment and don’t show any symptoms years later, even though they are still infected.

Organizers of the conference say the findings provide an argument for treating patients early. “(These studies) give us reason for enthusiasm, that ultimately we are going to get to where we needed to go, which is to cure people  with HIV infection,” said Dr. Steven Deeks, an HIV expert at the University of California, San Francisco.

 

Source: Maggie Fox, NBC News

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Lab-Grown Blood Vessels May Improve Heart Bypass

 Researchers have grown small blood vessels in a lab using stem cells from fat gathered through liposuction. Such cultured blood vessels might someday play a role in transplant operations, including heart bypass surgery.

In bypass surgery, transplanted blood vessels are used to reroute blood around severely blocked arteries. Current techniques have limitations, however, and these preliminary study results suggest that tissue-engineered blood vessels might help doctors surmount certain hurdles, the researchers said.

Many more steps are involved before heart surgery patients can benefit from this technique, said study author Dr. Matthias Nollert, an associate professor at the University of Oklahoma School of Chemical, Biological and Materials Engineering, in Norman, Okla.

“First, we will need to make a fully functional vessel. Ours works, but does not yet achieve physiological mechanical properties,” he said. “[Then] we will need to show that stem cells obtained from old, sick people can also be used to make a functional vessel and that this works in an animal model.”

All in all, “we are still five to 10 years away from seeing this being tested in people,” Nollert said. But the researchers hope to have a prototype ready for animal testing by early next year.

Ultimately, millions of patients with cardiovascular disease could benefit, the researchers said.

“We are targeting elderly, obese or diabetic patients in need of coronary artery bypass graft surgery,” Nollert said. “For these patients, the gold standard is a vascular graft, but for many there are no suitable vessels available.”

The findings are scheduled for presentation Wednesday at an American Heart Association meeting in New Orleans. Data and conclusions presented at medical meetings should be considered preliminary until published in a peer-reviewed medical journal.

For the study, researchers using liposuction extracted adult stem cells from fat and turned them into smooth muscle cells. Adult stem cells are considered to be undifferentiated, which means they hold the potential to morph into specialized cell types. Liposuction is a common cosmetic surgery procedure in which doctors use a small needle to remove excess fat from under the skin by suction.

The extracted cells were “seeded” onto a very thin collagen membrane. As they multiplied, researchers rolled them into tubes with the diameter of small blood vessels (3 millimeters). In three to four weeks, they were able to grow usable blood vessels.

Such lab-grown vessels with “off-the-shelf availability” could overcome problems associated with grafting blood vessels from the patient’s body or from using artificial blood vessels, the researchers believe.

Many bypass patients are readmitted to the hospital because of complications from surgery, and about 40 percent of these readmissions are caused by problems at the donor site, not the heart artery, Nollert said.

“By developing a tissue-engineered vessel using the patient’s own cells, we would eliminate the need to use a donor vessel,” he said.

Current small-vessel grafts also carry an inherent risk of clotting, rejection or failure to function normally, he added.

Other experts agree that engineered blood vessels could fill a need for patients with cardiovascular disease.

“It is very hard to bypass small vessels in the heart,” said Dr. Roberto Bolli, an American Heart Association spokesman and chief of cardiology at the University of Louisville in Kentucky. “If these cells prove useful, it will be very easy to collect through liposuction.”

One potential downside is that these blood vessels take time to grow in the lab. “They would not be available immediately, but you could bank your own cells and keep them until the time comes that you need them,” Bolli added.

Dr. Stephen Green, chief of cardiology at North Shore University Hospital in Manhasset, N.Y., is cautiously optimistic about the implications of the new findings.

“It’s a big deal and a potentially game-changing thing,” he said. “But this is a first step, and we are far removed from Mrs. Jones having bypass [surgery] with a lab-grown blood vessel.”

The need for the small-diameter blood vessels is tremendous, Green said. Many bypass patients don’t have veins to use. “You can run out of appropriate veins,” he said, “especially if this is a repeat operation.”

Source: Denise Mann, U.S. News Health


Cord blood cells may prove valuable for treatment of neurological diseases

Cells from blood that remains in the placenta and umbilical cord after childbirth have been used to treat a variety of illnesses, from cancer and immune disorders to blood and metabolic diseases. 

Now, scientists at the Salk Institute for Biological Studies have found a new way-using a single protein, known as a transcription factor-to convert cord blood (CB) cells into neuron-like cells that may prove valuable for the treatment of a wide range of neurological conditions, including stroke, traumatic brain injury and spinal cord injury.

The researchers demonstrated that these CB cells can be switched to ectodermal cells, outer layer cells from which brain, spinal and nerve cells arise.

“This study shows for the first time the direct conversion of a pure population of human cord blood cells into cells of neuronal lineage by the forced expression of a single transcription factor,” said Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory, who led the research team.

The study was collaborated with Fred H. Gage, a professor in Salk’s Laboratory of Genetics, and his team.

“Unlike previous studies, where multiple transcription factors were necessary to convert skin cells into neurons, our method requires only one transcription factor to convert CB cells into functional neurons,” said Gage.

The Salk researchers used a retrovirus to introduce Sox2, a transcription factor that acts as a switch in neuronal development, into CB cells. After culturing them in the laboratory, they discovered colonies of cells expressing neuronal markers.

Using a variety of tests, they determined that the new cells, called induced neuronal-like cells (iNC), could transmit electrical impulses, signalling that the cells were mature and functional neurons. Additionally, they transferred the Sox2-infused CB cells to a mouse brain and found that they integrated into the existing mouse neuronal network and were capable of transmitting electrical signals like mature functional neurons.

“We also show that the CB-derived neuronal cells can be expanded under certain conditions and still retain the ability to differentiate into more mature neurons both in the lab and in a mouse brain,” stated Mo Li, a scientist in Belmonte’s lab and a co-first author on the paper with Alessandra Giorgetti, of the Center for Regenerative Medicine, in Barcelona, and Carol Marchetto of Gage’s lab.

“Although the cells we developed were not for a specific lineage-for example, motor neurons or mid-brain neurons-we hope to generate clinically relevant neuronal subtypes in the future,” he added.

Importantly, said Marchetto, “We could use these cells in the future for modeling neurological diseases such as autism, schizophrenia, Parkinson’s or Alzheimer’s disease.”

Cord blood cells, noted Giorgetti, offer a number of advantages over other types of stem cells. First, they are not embryonic stem cells and thus they are not controversial. They are more plastic, or flexible, than adult stem cells from sources like bone marrow, which may make them easier to convert into specific cell lineages. The collection of CB cells is safe and painless and poses no risk to the donor, and they can be stored in blood banks for later use.

“If our protocol is developed into a clinical application, it could aid in future cell-replacement therapies,” said Li.

Source: ANI / Yahoo News India


Cord Blood Stem Cells Restore Toddler’s Hearing

A virus infection Stephanie Connor acquired during pregnancy put her unborn daughter at significant risk for brain damage and lifelong hearing loss. 

“It was traumatic,” said Connor, of LaBelle, Fl, after learning about her daughter’s condition. “It was like mourning the loss of a child.”

At age 1, baby Madeleine was completely deaf in her right ear and her hearing was severely lost in the left, said Connor. While a hearing aid helped to amplify some sounds for Madeleine, it would never fully repair the damage in her ear.

But a simple experimental procedure that Connor enrolled in for Madeleine may have restored her hearing and reversed her condition.

In January 2012, Madeleine, 2, became the first child to undergo an experimental hearing loss treatment through an FDA-approved trial at Memorial Hermann-Texas Medical Center that infused stem cells from her own banked cord blood into her damaged inner ear.

Within the last six months, Connor says she’s seen a dramatic improvement in Madeleine’s ability to hear.

“Before, when she would hear something she would look all around,” Connor said. “But now we notice that she turns in the right direction of the sound.”

Madeleine was also able to speak for the first time, Connor said.

For more than two decades, umbilical cord blood transplantation — either by a baby’s own cord blood or another’s, depending on the type of procedure — has been used to treat otherwise fatal diseases including blood disorders, immune diseases, and some types of cancers.

Infusing cord blood stem cells into the body may also have the potential to heal and regenerate damaged cells and tissues.

Regenerative therapy using cord blood stem cells is currently being studied as therapies to treat conditions including cerebral palsy and brain injury.

For the first time, doctors are experimenting with cord blood stem cells to regenerate hearing in children who have suffered hearing loss.

This yearlong study will follow 10 children, including Madeleine, ages 6 weeks to 18 months, who have acquired hearing loss and who have donated their cord blood to a registry.

“There are a number of treatments for hearing loss, but most of them rely on amplification of noises, not reversal of the hearing loss,” said Dr. Samer Fakhri, associate professor and program director in the Department of Otorhinolaryngology at Memorial Hermann-Texas Medical Center, and principal investigator of the study.

Since Madeleine is part of a study that is currently under way, it’s unclear whether Connor’s perceived improvement of Madeleine is really due to the stem cell procedure.

Madeleine has already had one follow-up appointment to test her speech and language development, which are indicators that her hearing has improved. She will have another one mid-July.

Fakhri said it’s still too early to determine whether the procedure benefitted Madeleine, or may be beneficial for other children.

“If there’s any improvement, it should be detected within six months to a year,” Fakhri said. “We can’t determine from just one child if there’s an overall benefit.”

If the study results show significant improvement overall among the collective children studied, children with acquired — not genetic — hearing loss, may be able to benefit from the procedure.

“We do not recommend that stem cells at this point now should be a treatment modality for hearing loss,” Fakhri said.

Previous studies in mice suggest long-term hearing repair after stem cell infusion. Fakhri says it’s likely that if the procedure works, children like Madeleine will have long-term restored hearing.

“The way the stem cells work is they support repair,” said Fakhri. “Once you repair the damage, there’s no suggestion that it will dwindle over time.”

Connor said the improvement she has seen so far is enough that she is grateful that she enrolled in the trial, and she hopes the study will prove to be beneficial in repairing hearing loss so other children can be treated successfully.

“As a mom of special needs, if you’re able to help a child it’s huge,” she said. “There’s nothing that can compare to giving a child back something that’s been taken away.”

Source: Lara Salahi, Good Morning America