title: Olfactory ensheathing cell neurorestorotherapy for amyotrophic lateral sclerosis patients: benefits from multiple transplantations.
abstract: 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.
authors.affiliation: Center for Neurorestoratology, Beijing Rehabilitation Center, Beijing, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Haitao
authors.initials: H
authors.lastname: Xi
authors.forename: Qingmiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Yancheng
authors.initials: Y
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.forename: Yushui
authors.initials: Y
authors.lastname: Ren
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongyun
authors.initials: H
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000601:surgery*; D017690:Cell Transplantation / Q000379:methods*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology* / Q000503:physiopathology; D055815:Young Adult