intravenously. (Another Phase I/II open-label clinical trial by the same group evaluated the safety, tolerability, and therapeutic effects of transplanting the NurOwn cells into ALS patients; 12 patients were transplanted intrathecally or intramuscularly. Another Phase IIa dose-escalation trial was also started in 2013 in which another 12 ALS patients were administered NurOwn cells with both intramuscular and intrathecal injections with increasing doses. Both of these studies are still ongoing with no published results as of April 2014 (NCT01777646, NCT01051882).
Mexico
In Mexico at the Hospital San José Tecnológico de Monterrey, the method of transplanting blood-derived stem cells into the frontal cortex of ALS patients to target upper motor neurons was studied in 2005 to 2006 (NCT01933321). The study determined that the transplantation of blood-derived stem cells into the frontal cortex was well tolerated and safe. However, as detailed by the ALSUntangled group in 2010, due to variable treatment dosing between patients, tremendous variability in data, and a dearth of objective measures of safety or integrity of the transplants, these conclusions are questionable.
Spain
At the Universidad de Murcia in Murcia, Spain, Jimenez et al. studied the intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) in patients with ALS. BMNCs contain a broader range of cells than bone marrow–derived MSCs (NCT01254539, NCT00855400). BMNCs are the isolated mononuclear fraction of the bone marrow aspirate, which includes B cells, T cells, and monocytes of the immune system, in addition to MSCs and HSCs. In their Phase I trial, 11 patients were studied with no acceleration in disease progression, and spinal cord analysis showed a greater number of motoneurons in treated segments compared to untreated segments. Due to the safety and lack of significant adverse events in the treated population, a further Phase I/II study was initiated in 2010 and is ongoing with no published results as of April 2014.
Iran
Hamid Gourabi et al. at the Royan Institute in Iran are taking a three-pronged approach by having three separate trials studying the efficacy and safety of transplantation of MSC in patients with ALS intravenously, intraventricularly, and intrathecally (NCT01759797, NCT01759784, NCT01771640). So far, only one of these three studies has been completed and no results have been published, with also very little description on their methods to date.
Korea and China
Finally, both China and Korea also have clinical trials ongoing to study the effects of MSC transplantation in ALS patients. An et al. at the General Hospital of Chinese Armed Police Forces are currently studying the use of umbilical cord MSCs in ALS patients (NCT01494480), while Corestem Inc., in collaboration with Kim et al. at the Hanyang University Seoul Hospital, is studying the safety of transplanting HLA-haplo matched bone marrow–derived stem cells (HYNR-CS-Allo inj) via intrathecal injection (NCT01758510, NCT01363401). Again, both of these studies are ongoing with no published results to date.
Leslie Suen
Pablo Avalos
Doniel Drazin
Cedars-Sinai Medical Center
See Also: Clinical Trials, Ethics of; Clinical Trials Outside the United States; Clinical Trials, U.S.: Amyotrophic Lateral Sclerosis.
Further Readings
Hench, Larry L., Julian R. Jones, and Michael B. Fenn, eds. New Materials and Technologies for Healthcare. London: Imperial College Press, 2012.
Mazzini, L., et al. “Mesenchymal Stem Cell Transplantation in Amyotrophic Lateral Sclerosis: A Phase I Clinical Trial.” Experimental Neurology, v.223/1 (2010).
Svendsen, Clive, et al. “The Past, Present, and Future of Stem Cell Clinical Trials for ALS.” Experimental Neurology (in press).
Clinical Trials Outside the United States: Cerebral Palsy
Clinical Trials Outside the United States: Cerebral Palsy
289
291
Clinical Trials Outside the United States: Cerebral Palsy
Cerebral palsy (CP) is the broad heterogeneous term used for a group of permanent, nonprogressive movement disorders that cause varying degrees of physical disability that typically involve body movement variations. Individuals with cerebral palsy also may experience variations in sensations, communication deficits, difficulties with depth perception, cognitive alterations, learning disabilities, behavioral problems, and seizure disorders. There are subtypes of CP that are characterized by the type of impairment. The different types include spastic, ataxic, athetoid/dyskinetic, and mixed. The majority of individuals have spastic CP. Cerebral palsy is the most commonly occurring motor disability in childhood.
CP is caused by a variety of factors, including infection in pregnancy, hypoxia during birth, severe neonatal jaundice, Rh incompatibility, or genetic factors. CP is more common in male infants and African Americans. In the United States, 800,000 individuals are diagnosed with CP, with an additional 10,000 babies diagnosed annually. Cerebral palsy is estimated to be five to 10 more times likely in poor and middle-income countries.
According to the Cerebral Palsy International Research Foundation, CP research should be focused in one of the following areas: prevention, improvement of motor and cognitive abilities in children using transformational technologies, and prevention of secondary complications and improvement in the quality of life in adults with CP. International research endeavors should focus in these key identified areas.
According to the National Institutes of Health Clinical Trials Registry (2014), there are currently 465 listed clinical trials, including current research, completed research, terminated studies, and unverified status studies, in the database. Of these, 193 active, open clinical trials examining various treatments and symptom management techniques for cerebral palsy are currently being conducted worldwide. The majority of research on CP is being conducted in the United States (211 studies) and Europe (115 studies). Other foreign countries make up the remainder of the studies, with 50 in east Asia currently or previously conducted; 36 in the Middle East; 26 in Canada; and less than 6 per region or country being conducted in Africa, Mexico, south Asia, southeast Asia, South America, Pacifica, and north Asia. Clinical trials outside the United States concentrate on a variety of issues related to cerebral palsy, its symptoms, management, treatment, and potential cures (Table 1).
The use of stem cell transplants for cerebral palsy outside the United States has been performed in other counties despite a scientific gap in the literature on the safe use of stem cells for this purpose. Clinical trials have been conducted outside the United States to determine the safety, use, advantages, and disadvantages of stem cell use for treating CP. Previously, researchers in Mexico gave subjects granulocyte colony stimulating factor (G-CSF) in an attempt to stimulate bone marrow production of stem cells. Bone marrow was then harvested, and CD 34+ cells were purified and delivered via the intrathecal route. The result of this research has not been published.
Australia recently started its first clinical trial using stem cell transplantation. The United States currently has three clinical trials exploring the use of umbilical cord blood and stem cell transplantation for children with CP. The first U.S. clinical trial using sibling umbilical cord blood began recruiting participants
