Cord Blood Stem Cell Therapy for Cerebral Palsy in Clinical Trial

Aaron Saenz, Singularity Hub, April 8, 2010

Cerebral palsy is characterized by hypoxia/reperfusion induced damaged to the brain in the perinatal period. It is manifested in four main types: a) Spastic, which occurs in 70-80% of cases and is associated with damage to the corticospinal tract or the motor cortex; b) Ataxic, occurs in 10%, is associated with damage to the cerebrum, and causes deficiencies in walks, hearing and speech; c) Athetoid/dyskinetic is caused by injury to the to the extrapyramidal motor system and/or pyramidal tract and to the basal ganglia, it occurs in approximately 20% of cases. Cerebral palsy is a non-progressive disorder in which recovery does not occur and treatments revolve around addressing symptomology. The possibility of stem cell therapy for cerebral palsy was proposed by Cellmedicine several years ago and is discussed in this video http://www.youtube.com/watch?v=egRxgUXDN4Y .

One type of stem cell that has been used for cerebral palsy comes from the cord blood. Usually cord blood stem cells are used for treatment of hematological (blood) disorders such as leukemias or genetic metabolic conditions. Cellmedicine proposed the use of cord blood for conditions such as cerebral palsy http://www.translational-medicine.com/content/pdf/1479-5876-5-8.pdf because of: a) its superior growth factor producing ability to other types of adult stem cells; b) the possibility of using cord blood with minimal matching; and c) the ability of cord blood stem cells to directly differentiate into other types of cells relevant to cerebral palsy such as neurons and glial cells.

In order to test validity of the possibility that cord blood may be useful for such a condition, the developmental cycle that occurs with drugs has to be applied. That is, firstly animal data needs to support the possibility of efficacy, as well as the safety of the intervention. Secondly, pilot human studies are needed to determine if it is feasible to administer the cells in patients with the particular disease without possibility of adverse effects. Thirdly, formal clinical trials need to be initiated. These usually begin with Phase I trials that assess safety and maximally tolerated dose, Phase II trials that assess efficacy in a non-blinded manner, and Phase III trials that seek efficacy in a double-blind placebo-controlled manner.

Groups like Cellmedicine have been involved in treatment of patients with cord blood. Additionally, Dr. Joanne Kurtzburg from Duke has been using the patient's own cord blood in treatment of patients with cerebral palsy http://www.youtube.com/watch?v=xLmY7Ps65wQ. Both of these treatments were considered part of the "practice of medicine" and may be comparable to "pilot investigations" in that safety data was generated and the medical procedure for physically administering the cells was developed.

Today a group at the Medical College of Georgia announced initiation of Phase I/II Placebo-Controlled, Observer-Blinded, Crossover Study to Evaluate the Safety and Effectiveness of a Single, Autologous, Cord Blood Stem Cell Infusion for the Treatment of Cerebral Palsy in Children.

The trial involves 40 patients between ages 2-12 who are seizure-free and have clinical evidence of a non-progressive motor disability due to brain dysfunction. The subjects recruited will not have the ability to sit independently by one year of age or the ability to walk by 18 months of age.

Patients will be divided into 2 groups, with the first group receiving red-cell depleted, mononuclear cell enriched cord blood unit prepared for infusion (treatment) and the second being administered saline combined with the inert stem cell administration solution lacking stem cells. The observer and patient will not know who is receiving cells from which group.

The main observation endpoints of the trial will be safety of autologous (patient's own) cord blood infusion in children with cerebral palsy by repeated follow-up over one year with clinical and laboratory evaluations. The secondary endpoint will be determination of whether a beneficial effect has occurred in the recipients. This will be measured using a patient questionnaire and standardized Gross Motor Function Measure evaluation with effects anticipated to be seen within 3-4 months.

Conceptually this study is a very safe one because it is the patient's own cord blood stem cells that are being used. This however could also be a negative issue. There is some evidence that when stem cells from another individual (allogeneic) are used, it is the reaction between the recipient and donor that gives rise to production of numerous growth factors. Since this current treatment is only using the patient's own cells, it may be similar to simply adding your own blood back into you. The animal studies previously performed involved using human cord blood cells in mice lacking part of the immune system. Additionally they used much higher concentration of cord blood cells per kilogram of body weight. Regardless, it is very important to state that this study lays the groundwork for translation of numerous stem cell approaches that have previously been used for patient treatment outside of the US, for US approval.

Parents of patients interested in trial participation should contact James E Carroll, M.D. the Principle Investigator of the study at 706-721-3371 jcarroll@mcg.edu