Barcelona – Research using man-made, blood-forming stem cells has shown great promise in animal experiments in suppressing HIV.
But now a grant from the California Institute for Regenerative Medicine (CIRM) has funded a clinical trial using those bio-engineered stem cells to treat HIV patients who have lymphoma, a deadly cancer that eventually kills people with AIDS.
Timothy Brown was the first patient to ever be cured of HIV after a bone marrow transplant to treat his leukemia received. He is known as the ‘Berlin patient’.
By using blood transplants from the umbilical cords of individuals with a genetic resistance to HIV, Spanish medical professionals believe they can treat the virus, having proven the procedure successful with one patient.
Now, a 37-year-old man from Barcelona, who had been infected with the HIV virus in 2009, was cured of the condition after receiving a transplant of blood.
While unfortunately the man later died from cancer just three years later, having developed lymphoma, the Spanish medical team is still hugely encouraged by what it considers to be a breakthrough in the fight against HIV and related conditions, according to the Spanish news source El Mundo.
Doctors in Barcelona initially attempted the technique using the precedent of Timothy Brown, an HIV patient who developed leukemia before receiving experimental treatment in Berlin, the Spanish news site The Local reported.
Brown was given bone marrow from a donor who carried the resistance mutation from HIV. After the cancer treatment, the HIV virus had also disappeared.
According to The Local, the CCR5 Delta 35 mutation affects a protein in white blood cells and provides an estimated one percent of the human population with high resistance to infection from HIV.
Spanish doctors attempted to treat the lymphoma of the so-called “Barcelona patient” with chemotherapy and an auto-transplant of the cells, but were unable to find him a suitable bone marrow.
“We suggested a transplant of blood from an umbilical cord but from someone who had the mutation because we knew from ‘the Berlin patient’ that as well as [ending] the cancer, we could also eradicate HIV,” Rafael Duarte, the director of the Haematopoietic Transplant Programme at the Catalan Oncology Institute in Barcelona, told The Local.
Prior to the transplant, a patient’s blood cells are destroyed with chemotherapy before they are replaced with new cells, incorporating the mutation which means the HIV virus can no longer attach itself to them. For the Barcelona patient, stem cells from another donor were used in order to accelerate the regeneration process.
Eleven days after the transplant, the patient in Barcelona experienced recovery. Three months later, it was found that he was clear of the HIV virus.
Despite the unfortunate death of the patient from cancer, the procedure has led to the development of an ambitious project that is backed by Spain’s National Transplant Organization.
March 2015 marked the world’s first clinical trials of umbilical cord transplants for HIV patients with blood cancers.
Javier Martinez, a virologist from the research foundation Irsicaixa, stressed that the process is primarily designed to assist HIV patients suffering from cancer, but “this therapy does allow us to speculate about a cure for HIV,” he added.
Trials are already underway to gather more information. They started in March 2015.
To decide if it could be done or not a trial, it was necessary first to note that Spanish banks umbilical cord had samples that will carry a key mutation that is responsible for transferring protection against HIV. This is the genetic mutation CCR5 Delta 3 , a variation that acts as a shield against the AIDS virus. Cells carrying this variant areimpermeable to the pathogen.
That’s what was discovered, almost by chance, with the Berlin patient, ie, if a person receives bone (or cord blood) from another subject that carries this positive change, will renew your blood cells they are immune to HIV, the body that will end disappearing.
“We knew that Spain is a world power in number of cords and cellularity, because the collection protocol makes us samples with many cells needed for transplants in adults. So we decided to analyze those cells rich laces, 25,000 . To this end, we agreed with all the autonomous communities and cord banks, “he told WORLD Rafael Matesanz, director of the National Transplant Organization, which has funded the search with about 100,000 euros.
After one year evaluating cord by cord to see which of them carried the mutation , said Rafael Duarte, who was director of Hematopoietic Transplant Program at the Catalan Institute of Oncology (ICO) and is now head of Hematopoietic Transplantation Oncohematology and the Hospital Puerta Iron, “we have managed to identify this feature 157 units, representing 0.6% of the Spanish population.”
That elite cords, and a solution for those offers that require a transplant for hematologic problem, an option to cure HIV to those who, besides being HIV positive, develop a cancer of the blood. “This is not a therapy for any patient with HIV. Only is intended for those who in addition to the virus develop leukemia, lymphoma, etc,” explains Matesanz.
With antiretroviral treatments available, a general therapy umbilical cord blood is not viable. First, because there are few units worldwide who carry the mutation makes the infallible cells against the virus, and secondly because this type of transplantation is not without risks. According to overall figures in Europe the expected mortality from complications of transplant is between 20% and 25%.
This is only acceptable in patients with very serious blood disease , which if not treat them in a short time, to death. Furthermore, according a study of over 100 patients, those with HIV who have undergone a bone marrow transplant have a higher risk of complications than for people without HIV. Therefore, there is a therapy for all HIV-positive people but to very specific cases, “says Duarte.
For all this is important to test this treatment in the context of a clinical trial, said the hematologist, because the protocols are the same in the various hospitals where it is made, monitoring will be equal and once the results are available, allow you to learn from experience experts worldwide.
The trial, which will involve the Puerta de Hierro Hospital, the Gregorio Maranon (both in Madrid), the Catalan Institute of Oncology (ICO), and the Hospital La Fe de Valencia, along with cord blood banks and the ONT, It aims to recruit patients in two to five years. “The first patient is already in. It is discussed in Madrid not until later this year or early next, because previously required to go through a chemotherapy [to kill tumor cells in their bone] and a conditioner that take several weeks. This is a person with a type of lymphoma and HIV we do not want to give more information, “said Duarte, who is the principal investigator of this trial.
157 cords mutation CCR5 Delta 3 identified in Spain continue to be part of the international registration, REDMO, but is an advisory committee (formed by doctors in hospitals, banks cord and ONT) through a protocol established to decide what to do with them if they are claimed by researchers from another country well for an HIV-positive patient with a hematologic or problem for a person without carrying HIV, consistent with the cord and requires a medical problem as a leukemia or lymphoma.
The trial, scheduled for three years and with a budget of 150,000 euros provided by the Mutua Madrileña Foundation, is within an experimental framework. “It is looking for a high amount of healing but the proof of the hypothesis that this transplant can make HIV disappear. The implications are qualitative rather than quantitative.”
The same view Josep Maria Gatell, co-director of the XV European AIDS Conference being held these days in Barcelona, is shown “is interesting in terms of research, no practical way for the current treatment of patients with HIV.”