Motor Neuron Diseases
Motor Neuron Diseases (MNDs) encompass a group of rare pathologies that selectively affect motor neurons, the nerve cells responsible for controlling voluntary muscles. They can involve the upper motor neuron (central), the lower motor neuron (peripheral), or both. The most common form is Amyotrophic Lateral Sclerosis (ALS), but the group also includes hereditary pediatric forms such as Spinal Muscular Atrophy (SMA) and rare variants like SMARD1. Onset can occur in childhood or adulthood, with highly variable clinical presentations.
MNDs can be of genetic, sporadic, autoimmune (rare), or idiopathic origin. The pathogenetic mechanisms include alterations in proteostasis, oxidative stress, mitochondrial dysfunction, neuroinflammation, and defects in RNA processing. The fact that motor neurons are selectively involved suggests the hypothesis that all these diseases share a series of common pathogenetic molecular events, which could represent potential targets for therapeutic intervention.
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Progressive muscle weakness (distal or proximal)
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Muscle atrophy
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Fasciculations, cramps, spasticity
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Swallowing and speech disorders (dysphagia and dysarthria/dysphonia)
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Respiratory failure in advanced stages
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Preserved cognitive function in most forms, but possible frontotemporal involvement in some variants (e.g., ALS-FTD)
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Comprehensive neurological assessment
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EMG and nerve conduction studies (NCS)
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MRI and brain PET scan
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Targeted genetic analysis or NGS (Next-Generation Sequencing) panels
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Exclusion of differential diagnoses (e.g., myopathies, acquired neuropathies)
Available therapies
Currently, available therapies for motor neuron diseases range from disease-modifying pharmacological treatments to gene therapy, supported by a multidisciplinary approach aimed at improving patients’ quality of life.
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For ALS: Riluzole, Edaravone, and experimental/targeted therapies (e.g., Tofersen for SOD1 mutations).
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For SMA: Nusinersen, Onasemnogene abeparvovec, and Risdiplam.
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Multidisciplinary Support: Neurological, physiotherapeutic, respiratory, and nutritional management.
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Supportive Interventions: Non-invasive ventilation (NIV), PEG (Percutaneous Endoscopic Gastrostomy), and communication aids.
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Palliative Care: For the management of advanced symptoms.
Research in progress
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Gene and RNA-based therapies for genetic forms.
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Studies on diagnostic and prognostic biomarkers (e.g., NfL).
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Immunomodulatory and neuroprotective approaches.
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Organoids and in vitro models for testing new treatments
Contacts and informations
Prof.ssa Stefania Corti
stefania.corti@unimi.it
https://pubmed.ncbi.nlm.nih.gov/38636436/