It is a study from the renowned Duke University. The vision of the oncologist and hematologist specializing in bone marrow and stem cell transplantation Claudio Dufour and the story of Justino, a 7-year-old boy who is on the waiting list to participate in the trial. umbilical cord stem cells
At Duke University, one of the most recognized private universities in the United States and around the world, located in Durham, North Carolina, a clinical study is being carried out, for the treatment of children with autism spectrum disorder with umbilical cord blood autologous and allogeneic. It is led by Dr. Joanne Kurtzberg, a professor in the Department of Pediatrics, Duke University School of Medicine and scientific director of the Clinical Cell Therapy Program.
In dialogue with Infobae, Claudio Dufour, medical oncologist and hematologist, scientific president of cell therapies at the Asian Association of Transfusion Medicine and medical director of BioCells stem cell bank, explained: “According to information from Duke, cells are injected intravenously , most of the cells are filtered from the blood through the lungs, spleen, and liver, and the remaining cells face the blood-brain barrier. The number of cells that can reach the brain is important for the success of therapy; but it is not the cells per se that generate their action, but the products of their internal machinery that are substances called cytokines ”.
“Cytokines are chemical elements that are released from stem cells into the blood, and due to their small size, they cross the blood-brain barrier, made it impossible for the size of a cell that these cytokines have already entered the central nervous system (CNS). to fulfill its paracrine role (similar to the effect of hormones), as anti-inflammatory chemical elements on chronic inflammation, product of a disorder in the communications between neurons (CNS cells), which would interfere with normal neuron-neuron communication, and that then it would result in one of the possible causes of this heterogeneous alteration called autistic state ”, he added.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that appears early in life. Stereotypical autism behaviors include impaired social communication, repetitive behaviors, and restricted activities and interests. The causes of autism are heterogeneous; sometimes there is a genetic predisposition and other times it may be due to environmental exposures. Research has identified some differences in brain morphology and activation in patients with autism, but there is no drug or behavioral therapy that can cure the disorder.
Although autism can be diagnosed at any age, it is known as a “developmental disorder” because symptoms usually appear during the first two years of life. There are many types of treatment available and they can generally be divided into the following categories: approaches around behavior and communication, approaches around eating, medications, complementary and alternative medicine, and cord blood stem cell therapies.
As specified by the expert, for the treatment, a minimum cellular dose has not been established. However, Duke has cellularity regulations and quality controls for cryopreserved material. The size of the dose used for each child depends on the number of cells available in the stored umbilical cord blood. To be part of the Duke study, two Argentine patients who have their umbilical cord blood stored in BioCells have been accepted and enrolled on the waiting list, where all the regulations inherent to all quality controls, pre-collection, processing are met. and cryopreservation required by the institution.
Currently two Argentine children are on the waiting list to participate in this clinical study at Duke University. One of them is Justino, 7 years old. He cryopreserved cells from his umbilical cord in BioCells with Dr. Dufour, and thanks to this, and because he meets all the requirements to be part of the research, his future could improve significantly. His parents, Gerardo and Jésica, shared their story:
“We started with this crusade, with this fight since Justino was 2 years old, when he was diagnosed with ASD and from there we started with a series of therapies, going through different therapeutic centers, sometimes seeing great and small advances,” he began narrating a Infobae by Meet Gerardo Coria, Justino’s father. “Today we are wanting to enter this innovative treatment made available by Duke University, which we have high hopes for, but we are also aware that it is one more tool to provide Justino in addition to conventional therapy, which we will maintain,” he added .
For Jesica Lozano, the child’s mother, it is a way of hope: “Although we know that it is not a cure, because (autism) is a condition, we hope that with this treatment improvements will be seen for the objective we have to him who is his independence when he grows up. Therapies have to continue, we want to make that clear. Doing an alternative treatment does not mean that the child has to stop the therapies, that is very important, “she said in the interview in which Dr. Claudio Dufour was also present.
“We live these days with great anxiety, we are these days waiting for the final decision, regarding expectations. We always want the best for Justi, we want to give him all the possibilities that are within our reach, for his better development and, as Claudio (Dufour) explained, to be able to increase his cognitive and communication skills, also trying not to fly with expectation. We are aware that there are limitations, that this is still an investigation “, said Gerardo, and pointed out:” This is for life, it is our life struggle and we are moving forward. ” Jesica reinforced the idea: “Finding this alternative treatment that can help you is great hope for us.”
Dufour specified: “Dr. Joanne Kurtzberg, who is the scientific director, began to do studies with different brain lesions as early as 2006. Now the treatment protocol, which is still in the final stages as a clinical trial, is already very advanced. If it had not been for the COVID pandemic, it would probably have already been approved by the FDA (US regulatory entity) in this year they began, I suppose it could be next year ”.
The drafts began to be outlined in 2014, and there was a final review of the therapeutic evolution with the cells of the children who had been able to save their umbilical cord blood towards the end of 2019. Dr. Kurtzberg and her entire team have a very, very broad experience not only in autism spectrum disorder, but also in other diseases such as cerebral palsy. They have done different types of therapeutic trial schemes; even now this last time in 2017 they started a new trial with another type of stem cells that are mesenchymal. They are cells that are not the same as those that give rise to the elements in the blood.
“In the case of this child (Justino), his umbilical cord blood was collected at the time of birth by decision of father and mother, and what we have stored and cryopreserved in BioCells are the hematopoietic stem cells, that is, the ones that give origin to red and white blood cells and platelets ”, explained Dufour.
It is that according to what was explained by the expert in stem cells, a specialist in bone marrow transplantation and hematology, “for a few years now, the storage of umbilical cord tissue is already being done in the different banks of the world per se , whose structure has a vein and two arteries and these mesenchymal cells are located around these blood vessels, which have some actions similar to those that are thought to respond similar to those of umbilical cord blood since it is a more recent study which has only started in 2017 ”.
The goal of treatment
The intention of the treatment is to use the own stem cells from the umbilical cord of children diagnosed with an autism spectrum disorder and to demonstrate that they have a positive long-term effect.
“What we know from the point of view of Autism Spectrum Disorders (ASD), the most relevant to emphasize are developmental disabilities, where social and communicational problems occur, and some behavioral problems that may or may not be significant”, stated the hematologist.
“Duke University did the last evolutionary evolution in December of last year and there are several protocols in place, not just the Duke one, this is the one that specifically talks about Duke. I took out the cover of the international magazine, a journal on stem cell transplantation. What is highlighted in yellow is the most important: ‘The principles of this protocol, it is presumed that therapy with cells derived from umbilical cord blood may have the potential to alleviate all the symptoms of ASD by modulating the inflammatory processes that occur. they produce in the brains of these children ”, specified the medical director of BioCells. umbilical cord stem cells
The most important thing of all is that they initially hypothesize and that is what they are already demonstrating today is that infusing these patients with their own umbilical cord blood cells can offer protection and repair at the neural level, in the brain. of nerve cells and reduction of the inflammatory process that is associated with this disorder. A very important thing is the amount of cells that are going to be infused, it is the same if it were a stem cell transplant, they are infused as if it were a traditional transfusion, the cells that this patient has cryopreserved, and one of the most important things is that since Duke they maintain that there must be a total of nucleated cells between 1 – 5 x 10 to 7, and within these nucleated cells are the hematopoietic stem cells.
What is going to be submitted as umbilical cord blood cell therapy was determined for children from 24 months, that is, two years, up to 72 months or six years. It is necessary to have 3 very clear parameters: the diagnosis of an observational scheme that it really is an ASD, a Binet intelligence scale above 35 and they explain that it is a single infusion of the stem cells of the umbilical cord that are cryopreserved, where It requires that there is consent from the parents, that they can travel to Duke since the treatment is done there and that the parents or guardian of the child can communicate in English.
What would the treatment accomplish?
Umbilical cord stem cells produce – shown by Duke – neuroprotection and neurogeneration. What does this mean? “On the one hand, they help produce new blood vessels, hence the angiogenesis thing; they release substances similar to hormones, as we have in our body the thyroid hormone, insulin, etc; These substances called cytokines are those that would enter the brains of children and would be the ones that would stop these inflammatory processes, which are somehow, although it is a pathology that does not have a single cause, it would be one of the causes more important, slowing down the possibility that the brain and the communications between neurons are optimal ”, explained Dufour.
“On the other hand, it has immunomodulatory effects that also reduce inflammation; and on the other hand they also activate all the resident cells of the brain, which help in this specific treatment system with the cell level “, he added at the same time that he explained that” 25 children entered the initial protocol. “
To assess the boys who can enter and participate in the study, they warn they make different types of evaluations according to the age of the patient, they ask them different questions that they could answer or not. Regarding the therapy, they propose from Duke that it be feasible and that it does not cause any type of disorder in the therapy of these characteristics.
Initially it was an open trial, and in these cases they had to be evaluated (potential participants) through an adaptive behavior scale well known to neurologists and pediatricians, called Vineland, which assesses mental retardation, delays in development, functional weaknesses of different abilities, potential deficiencies in speech or language, and it is also specifically useful in ASD and in another similar pathology called Asperger’s Syndrome.
Between 2020 and 2021 they will have FDA approval and what was a clinical trial becomes a conventional therapy and may be open to be performed according to the regulations of each country in different cell therapy units.
What is relevant about Duke is that the advantages of stem cells from the umbilical cord are the anti-inflammatory properties that give it the ability to regulate that inflammatory process migrating through all that is the cerebral circulation. On the other hand, this infusion by secreting these cells, these spices of hormones (cytokines) promote the repair mechanism at the level of neurons affected by the chronic inflammatory process.
It has also been proven that the use of umbilical cord blood is easy to collect in principle in newborns who decide to do this; and that it has potential future uses that are being expanded more and more. This is what I was telling you about mesenchymal cells, which have similar effects but are another type of stem cells. This is what an umbilical cord looks like: the vein in blue and the two umbilical arteries; Around 80% of these mesenchymal cells are located here, and this is why BioCells and many umbilical cord blood banking centers are not only collecting blood as Justin did at the time, but also storing mesenchymals tissue.
What Duke is demonstrating with this advanced trial is that the use of hematopoietic cells in this case from umbilical blood and placenta has promoted in post-therapeutic studies an improvement in children’s behavior, better cognitive ability, and an interaction improved what is socialization; with an advanced process of progressive evaluations over time; controls are made that extend over the years.
According to Geraldine Dawson, Ph.D. and principal investigator at Duke University, “One of the most challenging things for parents of children with autistic state disorder is that there is a lot of information that is not reliable,” and now this center of higher studies has achieved that the advanced clinical trial is very close to achieving FDA clearance for open clinical use, having demonstrated a favorable outcome in the children who participated in the study.
Duke has a very high number of patients on the waiting list, which means that attendees have to wait for treatments for more than 12 months. They are having between 1 year and 1 and a half years of waiting. The protocol was designed and has shown the best effects between 2 and 6 years of age. That is why we were so concerned about speeding up the times since Justino in February turns 8. Although they are still demonstrating with the initial stage that began in 2017 where they extended with the mesenchymal cells until the age of 11, that the results apparently although they are very preliminary are also optimal.
According to Dufour, “We in Argentina have the pertinent professional human resources and the pertinent therapeutic units, for which today it would be very difficult to be able to do it in the country because it would require, since it is still a clinical trial not authorized at an international level, as can Being the FDA in the United States, it would take us much longer as a compassionate use clinical trial than the chances of this young man (Justino) going to Duke. Once this is approved at the international level, it would allow us to limit waiting times.
“Justino is not the only child, there are two youngsters who have their cells cryopreserved in BioCells and who are on the waiting list for this treatment,” Dufour specified.
Duke publications on children treated with umbilical cord stem cell therapy provide information on improvements in communication and behavior. According to the hematologist, “it is expected that Duke’s clinical trial protocol will soon obtain FDA approval, and then go on to open therapeutics approved for clinical use.”
From the BioCells medical direction, it is expected that the protocols will go to the clinical stage in origin, and that by demonstrating the technical-scientific capacity of Argentina, in the near future it will be possible to carry out these promising treatment options in our country. To achieve this, agreements are being made with different laboratories and public organizations to provide a framework for this important project.