Low intensity exercise training in patients with amyotrophic lateral sclerosis - factors influencing eligibility and compliance to the clinical trial.

BACKGROUND: To date, there are no evidence-based recommendations for physical therapy in amyotrophic lateral sclerosis (ALS). The reason is a low number of related clinical trials (CTs), restricted sample sizes and a high dropout rate. It may influence the profile of the participants, while the final results might not translate to the general ALS population. OBJECTIVE: To analyze factors affecting the ALS patients' enrollment and retention to the study, and to describe a profile of participants as compared to the eligible group. METHODS: A total of 104 ALS patients were offered participation in a CT of low-intensity exercises at home. Forty-six patients were recruited. Demographic and clinical data (El Escorial criteria, site of onset, diagnosis delay, disease duration, amyotrophic lateral sclerosis functional rating scale - revised [ALSFRS-R], Medical Research Council [MRC], hand-held dynamometry) were analyzed every 3 months. RESULTS: Male gender, younger age and a higher ALSFRS predicted enrollment, while male gender, higher ALSFRS-R and MRC predicted retention in the study. A long commute to the study site and a fast disease progression were the main reasons influencing both enrollment and retention. Despite a high dropout rate, study participants were representative for the general ALS population. CONCLUSION: The above demographic, clinical and logistic factors need to be considered when designing studies in ALS population.

Potential Preventive Strategies for Amyotrophic Lateral Sclerosis.

It may seem useless to propose preventive measures for a disease without established pathogenesis and successful therapy, such as amyotrophic lateral sclerosis (ALS). However, we will show that ALS shares essential molecular mechanisms with aging and that established anti-aging strategies, such as healthy diet or individually adjusted exercise, may be successfully applied to ameliorate the condition of ALS patients. These strategies might be applied for prevention if persons at ALS risk could be identified early enough. Recent research advances indicate that this may happen soon.

Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally.

Intrathecal application of neuroectodermally converted stem cells into a mouse model of ALS: limited intraparenchymal migration and survival narrows therapeutic effects.

Stem and progenitor cells provide a promising therapeutic strategy for amyotrophic lateral sclerosis (ALS). To comparatively evaluate the therapeutic potentials of human bone marrow-derived mesodermal stromal cells (hMSCs) and umbilical cord blood cells (hUBCs) in ALS, we transplanted hMSCs and hUBCs and their neuroectodermal derivatives (hMSC-NSCs and hUBC-NSCs) into the ALS mouse model over-expressing the G93A mutant of the human SOD1 gene. We used a standardized protocol similar to clinical studies by performing a power calculation to estimate sample size prior to transplantation, matching the treatment groups for gender and hSOD-G93A gene content, and applying a novel method for directly injecting 100,000 cells into the CSF (the cisterna magna). Ten days after transplantation we found many cells within the subarachnoidal space ranging from frontal basal cisterns back to the cisterna magna, but only a few cells around the spinal cord. hMSCs and hMSC-NSCs were also located within the Purkinje cell layer. Intrathecal cell application did not affect survival times of mice compared to controls. Consistently, time of disease onset and first pareses, death weight, and motor neuron count in lumbar spinal cord did not vary between treatment groups. Interestingly, transplantation of hMSCs led to an increase of pre-symptomatic motor performance compared to controls in female animals. The negative outcome of the present study is most likely due to insufficient cell numbers within the affected brain regions (mainly the spinal cord). Further experiments defining the optimal cell dose, time point and route of application and particularly strategies to improve the homing of transplanted cells towards the CNS region of interest are warranted to define the therapeutic potential of mesodermal stem cells for the treatment of ALS.