Newsletter - July 2014


July is Cord Blood Awareness Month:

Latest Cord Blood Trial Targets Autism

Geraldine Dawson, PhD, & Joanne Kurtzberg, MD

Photo Credit: Geraldine Dawson, PhD, and Joanne Kurtzberg, MD. Photo taken by Jared Lazarus and released by Duke Medicine News and Communications

The latest clinical trial to explore the therapeutic potential of cord blood launched this month with a focus on autism. This is a very big deal because autism is a very common condition. In recent years the number of children with autism has been rising, and no one knows why. A few months ago the CDC upgraded the prevalence of autism in children age eight from 1 in 88 to 1 in 68; among boys the prevalence is 1 in 42.

Basically, we all know someone with autism. If cord blood stem cells are beneficial as an autism intervention, it will turn "cord blood banking" into a household phrase.

But right now the research is at a very early stage of study. The new autism trial will look at the safety and efficacy of giving their own cord blood to 20 children between ages 2 and 6 years. This trial is open to any child, worldwide, who has their own cord blood in storage and meets the trial criteria. There is no control group in this trial, every child will receive the stem cell therapy and then have follow ups at 6 and 12 months. That being said, the first children going into treatment have been on a waiting list, so new applicants will have to wait for the next autism trial.

The home of this trial is at Duke Medical Center in Durham, North Carolina, USA. The funding for the trial (more about that funding later) was awarded to Duke's Robertson Cell and Translational Therapy Program, under lead investigator Dr. Joanne Kurtzberg. Another important leader of the trial is Dr. Geraldine Dawson, the director of the Duke Center for Autism and Brain Development.

The idea that cord blood stem cells could be used to treat autism is an outgrowth of extensive previous research at Duke using cord blood to treat cerebral palsy and its precursor hypoxic ischemic encephalopathy (HIE). Dr. Kurtzberg's group has treated hundreds of children with acquired neurologic disorders (PMC3816574, NCT01147653) and found that the patient's own umbilical cord blood (UCB) "has been shown to lessen the clinical and radiographic impact of hypoxic brain injury and stroke in animal models and in infants with hypoxic ischemic encephalopathy. UCB also engrafts and differentiates in the brain, facilitating neural cell repair in animal models and human patients...". (NCT02176317)

The trial proposal states: "In this (autism) study, the investigators hypothesize that infusion of a patient's own umbilical cord blood cells can offer neural protection/repair in the brain and reduction of inflammation associated with this (autism) disorder." (parentheses added)

Autism Spectrum Disorder (ASD) is similar to cerebral palsy (CP) in that it is a neurodevelopment disorder with early onset in life. Currently, available biomedical treatments for patients with ASD are supportive, but not curative.

Nonetheless, the leap from treating CP to ASD is significant. CP is often diagnosed within the first year of life, as the baby misses milestones in motor skills or displays muscle tone problems such as rigidity or spasticity. The diagnosis of ASD requires testing the child's language and social skills, and therefore often is not picked up until somewhere between two and three years of age.

Prior to 2013, the label "autism" covered a constellation of conditions with separate diagnostic codes, such as Asperger syndrome and Pervasive Developmental Disorder (PDD). However, the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) did away with those separate labels and placed all autism disorders on a spectrum with a single diagnostic code.

The diagnosis of Autism Spectrum Disorder (ASD) is based on difficulties in social communication and repetitive behaviors. There is a saying in this community that "If you have met one person with autism, then you have met one person with autism" - because each case is unique. Nonetheless, research has shown that the new DSM-5 criteria are capturing the wide range of individuals with autism, from low functioning to high functioning.

New clinical trials in the United States require high dose infusions of funding. Initially, the autism cord blood clinical trial received a two year grant from PerkinElmer, the parent company of the ViaCord family cord blood bank. PerkinElmer is not restricting eligibility for this trial to their own clients, it is open to all patients who qualify.

Duke is the ideal center to research stem cell therapy for autism because they possess the combined skills of Dr. Kurtzberg and Dr. Dawson. Obviously Dr. Kurtzberg is well known as a pioneer in new applications of cord blood therapy. Dr. Dawson was recruited to Duke in Aug. 2013 after she had founded the University of Washington Autism Center and then served as Chief Science Officer at Autism Speaks. Dr. Dawson has designed many of the tests that will be used to measure the efficacy of cord blood stem cells for treating autism. This clinical trial will examine not only whether the therapy changes the behavior of children with autism, but also whether it reshapes the patterns of their brain activity that are visible in brain imaging.

The autism trial using autologous cord blood is only the first step in Duke's long term plans for their cell therapy program. The next step is to conduct clinical trials for acquired neurologic disorders using allogeneic (donated) cord blood. The transition to treatment with donated cells will make therapy accessible to many more patients who do not have their own cord blood in storage. The ultimate goal of the Duke program is for the FDA to approve acquired neurologic disorders as an indication for use of the FDA-licensed cord blood units in the public cord blood bank at Duke (product name Ducord).

In the spring of 2014 the Marcus Foundation announced a commitment to give $15 million to advance cord blood research at Duke. This generous gift will cover the first two years of a planned five-year research program that will cost about $41 million in total. Drs. Kurtzberg and Dawson have designed a series of additional clinical trials that further explore the use of cord blood for autism and will launch the use of donated cord blood for acquired neurological disorders. The planned program will treat a total of 390 children and adults with autism, 100 children with cerebral palsy and 90 adults who had a stroke.

The impact of this grant will be transformative. Currently in the USA there are some 2 million people with Autism Spectrum Disorder, 764,000 children and young adults with cerebral palsy, and stroke kills an average of nearly 130,000 people per year.

Established by Bernie Marcus, co-founder of Home Depot, The Marcus Foundation has a prestigious history of supporting autism research. The work of the Marcus Foundation is inspired in part by the memory of Mark S. Niziak, Jr. ("Marcus"), who died at age five of a brain tumor. The Marcus Foundation opened the Marcus Autism Center in Atlanta in 1991 and donated the funds to start the Autism Speaks advocacy organization in 2005.

In a press release for Duke, Dr. Kurtzberg said, "The whole program has enormous potential... Autism, stroke and cerebral palsy are all neurologic conditions that impair function and quality of life for these children and adults. If we can make that better, it will have a huge personal and societal impact."

This article was based on previous press releases from Duke, PerkinElmer, and the Marcus Foundation, as well as web surfing on the topics covered. This story is personal for me because ASD runs in my family, including two of my first degree relatives. -- Frances Verter, PhD, founder of the Parent's Guide to Cord Blood Foundation.


Cord Blood Clinical Trials for Novel Indications through 2012

David S. Allan M.D.

David S. Allan MD, Ottawa Hospital Research Institute

Umbilical cord blood has been identified as a rich source of blood-forming stem cells that can be used to restore normal blood development following blood stem cell transplantation. In particular, umbilical cord blood is most commonly used in pediatric patients undergoing blood stem cell transplantation for blood cancers such as leukemia and for the treatment of rare inherited metabolic disorders.

In addition to blood-forming stem cells, umbilical cord blood contains other progenitor cells that may be useful in the treatment of organ injury or to dampen immune responses in a range of novel indications. To better understand the field of studies that have been performed for these novel indications, we performed a systematic scoping review of the literature and clinical trial registries through the end of 2012. We examined the PubMed, EMBASE and Cochrane databases of publications, and trials registered with or the WHO's platform ICTRP.

We identified a total of 20 published studies using umbilical cord blood cells and 47 ongoing clinical trials that had not yet completed enrolment. The types of disorders that were being studied cover: neurological disorders including autism, cerebral palsy and spinal cord injury, cardiac and vascular disorders, liver disease and immune conditions such as diabetes.

Most of the studies in our survey infused cord blood cells without selecting specialized cell types and without growing cells in the laboratory. Several studies reported on the use of mesenchymal stem cells (MSCs) that were grown in culture from cord blood cells. MSCs have been shown to repair damaged tissues in many previous studies and can modulate immune responses in autoimmune conditions. Although other cells types such as endothelial progenitors have been identified in cord blood, these cells have not been studied in cord blood transplantation trials to date.

The studies published through the end of 2012 contained 317 patients who had received umbilical cord blood transplants for novel indications. This limited numbr of patients were treated for a broad range of conditions. The cord blood stem cells came from both public and family cord blood banks, and the patients included both adults and children.

Only a minority of these preliminary studies included a control group (only 3 of the 20 published studies) which limits the ability to know how useful these transplants were compared with standard treatments. Many studies reported possible benefit (reported in 15 of 20 studies) but the true benefits remain unknown given the small number of patients enrolled and it is common that negative studies are often never published. In order to really know whether these approaches are beneficial, randomized studies will be required in the future.

While these studies provide hope that cord blood may be useful for the treatment of these devastating conditions, more studies are needed and will need to be repeated by several groups before we can embrace these transplant strategies. Importantly, future studies need to be conducted using the highest standards in clinical trial design to provide the greatest confidence regarding these risky and cost-intensive strategies.

It remains unknown whether family banking of cord blood is recommended for treatment of these new indications. With increasing banking of cord blood units in public and private banks, there is an urgency to increase our knowledge of how best to use these cells to improve the health of patients in need of regenerative therapy or immune modulation.

MAJ Iafolla, J Tay, DS Allan Biology of Blood and Marrow Transplantation 2014 Jan;20(1):20-5 PMID24067504

Dr. David S. Allan MD FRCP(C) is a scientist in the Regenerative Medicine Program at the Ottawa Hospital Research Institute (OHRI) and a hematologist with the Blood and Marrow Transplant Program at The Ottawa Hospital. In addition, he is a medical director with the National Public Cord Blood Bank at Canadian Blood Services. Dr. Allan is a Queen's graduate and completed his residency in Internal Medicine and Hematology at the University of Toronto and the University of Western Ontario. Dr. Allan completed a clinical fellowship in blood and marrow transplantation at the Hôpital Maisonneuve-Rosemont in Montréal before joining OHRI in 2005. His research program focuses on experimental cell therapy using blood stem cells.