Testing Cord Blood Stem Cells as a Treatment for Cerebral Palsy


The Cord Blood Registry (CBR) has announced partnerships with the University of Texas Health Science Center at Houston and Georgia Regents University to establish FDA-regulated clinical trials to test the efficacy of intravenous infusions of umbilical cord blood in children with cerebral palsy.

According to statistics from the Center for Disease Control (CDC), one in every 323 children in the United States has been diagnosed with cerebral palsy or related disorders that affect movements, balance, and posture.

In these proposed clinical trials, a child who has been diagnosed with cerebral palsy-type disorders will receive intravenous infusions of their own umbilical cord blood that was banked at the time of their birth.

Because cerebral palsy results from abnormal brain development or brain damage to the motor centers of the developing brain, umbilical cord blood treatments might provide the means to help the brain heal itself. These umbilical cord blood treatments will take place along side more traditional treatments such as surgery, medications, orthopedic braces, and physical, occupational, and speech therapies.

New Clinical Trial to Examine Stem Cell Treatment for Cerebral Palsy in Children


A new clinical trial that is probably one of the first of its kind will study two types of stem cell treatments for children who have cerebral palsy. The University of Texas Health Science Center at Houston (UTHealth) Medical School will host this trial.

This trial will be conducted in a blinded fashion and will test the efficacy of stem cells against a placebo. The types of stem cells investigated in this clinical trial include banked cord blood stem cells and bone marrow stem cells. Charles S. Cox Jr., M.D., professor of pediatric surgery at the UTHealth Medical School and director of the Pediatric Trauma Program at Children’s Memorial Hermann Hospital will lead this clinical trial, and Sean I. Savitz, M.D., chair of the UTHealth Department of Neurology will serve as the co-principal investigator.

This FDA-approved study builds on Dr. Cox’s previous work on traumatic brain injury and the use of stem cell therapy to treat it in children and adults. In particular, Cox has focuses on those patients who have been admitted to Children’s Memorial Hermann and Memorial Hermann-Texas Medical Center after having suffered a traumatic brain injury. Prior research by Cox and others have shown that stem cells derived from a patient’s own bone marrow can be used safely used in pediatric patients with traumatic brain injury. In this clinical trial, Cox is also studying cord blood stem cell treatment for these injuries in a separate clinical trial.

Cox’s trials will enroll a total of 30 children between the ages of 2 and 10 who have cerebral palsy. 15 of these subjects have will have their own cord blood banked at Cord Blood Registry (CBR), and 15 will not have banked any cord blood. In each of these groups, five subjects will be randomized to a placebo control group.

After treatment the children will be neurologically assessed at six, 12 and 24 months. None of the parents will be told if their child received stem cells or a placebo until the 12-month follow-up exam, and at this time, those parents whose children received the placebo may elect to have their child receive a stem cell treatment either by means of stem cells isolated from bone marrow harvest or with stem cells from cord blood banked with CBR.

Collaborators in the study include CBR, Let’s Cure CP, TIRR Foundation and Children’s Memorial Hermann Hospital.

The Transformation of Ordinary Skin Cells into Functional Brain Cells


A paper in Nature Biotechnology from research groups at Case Western Reserve School of Medicine describes a technique that directly converts skin cells to the specific type of brain cells that suffer destruction in patients with multiple sclerosis, cerebral palsy, and other so-called myelin disorders. This particular breakthrough now enables “on demand” production of those cells that wrap or “myelinate” the axons of neurons.

Myelin is a sheath that wraps the extension of neurons called the axons. Neurons are the conductive cells that initiate and propagate nerve impulses. Neurons contain cell extensions known as axons that connect with other neurons. The nerve impulse runs from the base of the cell body of the neurons, down the axon, to the neuron to which it is connected. An insulating myelin sheath that surrounds the axon increases the speed at which nerve impulses move down the axon. When this myelin sheath is damaged, nerve impulse conduction goes awry as does nerve function. For example, patients with multiple sclerosis (MS), cerebral palsy (CP), and rare genetic disorders called leukodystrophies, myelinating cells are destroyed are not replaced.

neuron

The new technique discussed in this Nature Biotechnology paper, directly converts skin cells called fibroblasts, which are rather abundant in the skin and most organs, into oligodendrocytes, the type of cell that constructs the myelin sheath in the central nervous system.

Oligodendrocyte

“Its ‘cellular alchemy,'” explains Paul Tesar, PhD, assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine and senior author of the study. “We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy.”

Tesar and his group used a technique called “cellular reprogramming,” to manipulate the levels of three naturally occurring proteins to induce the fibroblasts to differentiate into the cellular precursors to oligodendrocytes (called oligodendrocyte progenitor cells, or OPCs).

OPCs

Led by Case Western Reserve researchers and co-first authors Fadi Najm and Angela Lager, Tesar’s research team rapidly generated billions of these induced OPCs (called iOPCs). They demonstrated that iOPCs could regenerate new myelin coatings around nerves after being transplanted to mice—a result that offers hope the technique might be used to treat human myelin disorders.

Demyelinating diseases damage the oligodendrocytes and cause loss of the insulating myelin coating. A cure for these diseases requires replacement of the myelin coating by replacement oligodendrocytes.

Until now, OPCs and oligodendrocytes could only be obtained from fetal tissue or pluripotent stem cells. These techniques have been valuable, but have distinct limitations.

“The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes,” explains co-author and myelin expert Robert Miller, PhD, professor of neurosciences at the Case Western Reserve School of Medicine and the university’s vice president for research. “The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells.”

Even though this initial study used mouse cells, the next critical next step is to demonstrate feasibility and safety of human cells in a laboratory setting. If successful, the technique could have widespread therapeutic application to human myelin disorders.

“The progression of stem cell biology is providing opportunities for clinical translation that a decade ago would not have been possible,” says Stanton Gerson, MD, professor of Medicine-Hematology/Oncology at the School of Medicine and director of the National Center for Regenerative Medicine and the UH Case Medical Center Seidman Cancer Center. “It is a real breakthrough.”