یک رویکرد درمانی بالقوه برای اسکلروز جانبی آمیوتروفیک
1- Introduction
2- Mesenchymal Stem Cell Characteristics
3- MSC Application in ALS Rodent Models
4- Is Autologous MSC Therapy Possible in ALS Patients?
5- MSC Administration in ALS Patients
6- Future Perspectives
7- Conclusions
References
Introduction
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by the selective degeneration of both upper (UMN) and lower motor neurons (LMN), causing both motor and extra-motor symptoms [1, 2]. LMNs are in the brainstem and spinal cord and transmit impulses from the UMNs to the muscles at the level of the neuromuscular synapses to innervate the skeletal muscles that control the arms and the legs. The main symptoms of ALS are muscle weakness, wasting, in particular in the limbs, cramps, twitching, and problems in speaking [3]. Specifically, UMN symptoms include weakness, speech difficulties, spasticity, and inappropriate emotionality, while LMN symptoms are represented by cramps, twitching, muscle wasting and weakness [3]. The patients can show an initial presentation with spinal-onset disease, which is the most common form characterized by limb muscle weakness, or with bulbaronset disease, whose characteristics are dysarthria and dysphagia [2, 3]. In Europe, the ALS incidence was estimated to be 2 to 3 cases per 100,000 individuals [2]. However, other than by a progressive and asymmetric weakness and atrophy in limb, thoracic, abdominal, and bulbar muscles, ALS is associated also with extrapyramidal features, postural abnormalities, small fiber neuropathy, and mild oculomotor disturbance [1]. Even if ALS main symptoms are correlated with motor dysfunction, about 50% of patients show also cognitive and behavioural impairment [2]. Usually, ALS leads to death within 3–5 years [1, 2]. Respiratory failure is recognized as one of the main complications of ALS and one of the main causes leading to death [4, 5]. The appearance of respiratory failure is caused by the impairment of the respiratory musculature, and it is influenced by the concomitant presence of other respiratory pathologies [4, 5]. The loss of function of the phrenic nerve induces diaphragm weakness, leading as a consequence to dyspnea, orthopnea, and hypoventilation [4].