Olfactory ensheathing cell neurorestorotherapy for amyotrophic lateral sclerosis patients: benefits from multiple transplantations.

Our previous series of studies have proven that olfactory ensheathing cell (OEC) transplantation appears to be able to slow the rate of clinical progression after OEC transplantation in the first 4 months and cell intracranial (key points for neural network restoration, KPNNR) and/or intraspinal (impaired segments) implants provide benefit for patients (including both the bulbar onset and limb onset subtypes) with amyotrophic lateral sclerosis (ALS). Here we report the results of cell therapy in patients with ALS on the basis of long-term observation following multiple transplants. From March of 2003 to January of 2010, 507 ALS patients received our cellular treatment. Among them, 42 patients underwent further OEC therapy by the route of KPNNR for two or more times (two times in 35 patients, three times in 5 patients, four times in 1 patient, and five times in 1 patient). The time intervals are 13.1 (6-60) months between the first therapy and the second one, 15.2 (8-24) months between the second therapy and the third one, 16 (6-26) months between the third therapy and the fourth one, and 9 months between the fourth therapy and the fifth time. All of the patients exhibited partial neurological functional recovery after each cell-based administration. Firstly, the scores of the ALS Functional Rating Scale (ALS-FRS) and ALS Norris Scale increased by 2.6 + 2.4 (0-8) and 4.9 + 5.2 (0-20) after the first treatment, 1.1 + 1.3 (0-5) and 2.3 + 2.9 (0-13) after the second treatment, 1.1 + 1.5 (0-4), and 3.4 + 6.9 (0-19) after the third treatment, 0.0 + 0.0 (0-0), and 2.5 + 3.5 (0-5) after the fourth treatment, and 1 point after the fifth cellular therapy, which were evaluated by independent neurologists. Secondly, the majority of patients have achieved improvement in electromyogram (EMG) assessments after the first, second, third, and fourth cell transplantation. After the first treatment, among the 42 patients, 36 (85.7%) patients' EMG test results improved, the remaining 6 (14.3%) patients' EMG results showed no remarkable change. After the second treatment, of the 42 patients, 30 (71.4%) patients' EMG results improved, 11 (26.2%) patients showed no remarkable change, and 1 (2.4%) patient became worse. After the third treatment, out of the 7 patients, 4 (57.1%) patients improved, while the remaining 3 (42.9%) patients showed no change. Thirdly, the patients have partially recovered their breathing ability as demonstrated by pulmonary functional tests. After the first treatment, 20 (47.6%) patients' pulmonary function ameliorated. After the second treatment, 18 (42.9%) patients' pulmonary function improved. After the third treatment, 2 (28.6%) patients recovered some pulmonary function. After the fourth and fifth treatment, patients' pulmonary function did not reveal significant change. The results show that multiple doses of cellular therapy definitely serve as a positive role in the treatment of ALS. This repeated and periodic cell-based therapy is strongly recommended for the patients, for better controlling this progressive deterioration disorder.

Intracranial transplant of olfactory ensheathing cells in children and adolescents with cerebral palsy: a randomized controlled clinical trial.

Successful repair of damage in cerebral palsy (CP) needs effective clinical interventions other than simply symptomatic treatments. To elucidate the feasibility of using olfactory ensheathing cells (OECs) to treat CP in children and adolescents, we conducted a randomized controlled clinical trial (RCT) on 33 patients. The patients were randomly assigned into two groups (treatment group, n = 18; control group, n = 15), and OECs derived from aborted fetal tissue were injected into the bilateral corona radiata in the frontal lobes (a key point for neural network restoration, KPNNR). The Gross Motor Function Measure (GMFM-66) and the Caregiver Questionnaire Scale were used to evaluate the patients' neurological function and overall health status. Among the 14 patients who completed the 6-month study, six received the cell transplantation and the other eight served as controls. In OEC treatment group, GMFM-66 scores were 26.67 +/- 25.33 compared with 19.00 +/- 20.00 for the control group. Concurrently, the Caregiver Questionnaire Scale score decreased to 77.83 +/- 15.99 in the treatment group in comparison to 138.66 +/- 64.06 of the control group. This trial, albeit small in sample size, indicates OEC KPNNR transplantation is effective for functional improvement in children and adolescents with CP, yet without obvious side effects. This small-scale study suggests that the procedure may be a plausible alternative method to treat this not yet curable disorder, and we urge further evaluation with a large-scale RCT.