Cette étude vise à explorer une nouvelle approche du traitement de la sclérose latérale amyotrophique (SLA) en améliorant l'administration d'un médicament appelé immunoglobuline intraveineuse (IgIV) directement au cortex moteur du cerveau. La SLA est une maladie grave qui affecte les cellules nerveuses du cerveau et de la moelle épinière, entraînant une perte de contrôle musculaire. L'étude se concentre sur six patients atteints de SLA pour voir si cette méthode est sûre et réalisable. En améliorant potentiellement la délivrance des IgIV, l'étude espère trouver une manière plus efficace de gérer les symptômes de la SLA et de ralentir la progression de la maladie. Les participants à l'étude recevront des IgIV à deux doses différentes. Le premier groupe de trois patients recevra une dose plus faible, tandis que le second groupe de trois recevra une dose plus élevée. Le traitement implique une procédure spécialisée où, lors de la deuxième dose, la barrière hémato-encéphalique est temporairement ouverte à l'aide d'ultrasons focalisés à travers un dispositif en forme de casque, permettant aux IgIV d'atteindre le cortex moteur plus efficacement. Cette procédure a lieu deux semaines après la première dose et utilise une combinaison d'ultrasons et d'une solution spéciale appelée microbulles. L'étude surveillera les participants pour la sécurité et l'efficacité du traitement sur 24 semaines par le biais de visites de suivi régulières.
Inclusion Criteria: 1. Diagnosed with ALS as per the Gold Coast Criteria; 2. Aged 18 years or older; 3. Capable of providing informed consent and complying with study procedures; 4. If taking Riluzole, on a stable dose for at least 4 weeks prior to Baseline; 5. If taking Edaravone, on a stable dose of one completed cycle prior to Baseline; 6. Respiratory Function Criterion: * Able to lie supine without BiPAP or breathing discomfort; OR * Forced vital capacity or slow vital capacity ≥50% of the predicted value for sex, height and age, if available 7. Able to communicate sensations during the Dome FUS procedure. 8. Qualified fit for the anesthesia by an anesthesiologist, ASA I-III. Exclusion Criteria: 1. MRI findings: 1. Active infection/inflammation 2. Acute or chronic hemorrhages, specifically \> 4 lobar microbleeds, and no siderosis or macrohemorrhages 3. Tumor/space occupying lesion causing significant mass effect 4. Meningeal enhancement 5. Intracranial hypotension 2. More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp 3. Clips or other metallic implanted objects in the skull or the brain, except shunts 4. Significant cardiac disease or unstable hemodynamic status including: 1. Documented myocardial infarction within six months of screening 2. Unstable angina on medication 3. Unstable or worsening congestive heart failure 4. Left ventricular ejection fraction below the lower limit of normal 5. History of a hemodynamically unstable cardiac arrhythmia 6. Cardiac pacemaker 7. Severe hypertension (diastolic BP \> 100 on medication) 8. Patient has right-to-left, bidirectional, or transient right-to-left cardiac shunts 9. QT prolongation observed on screening ECG (QTc \> 450 for men and \> 470 for women) 5. Uncontrolled hypertension (systolic \> 150 and diastolic BP \> 100 on medication) 6. Patients should not take medications known to increase risk of hemorrhage (e.g., aspirin or class I and III anticoagulants) for at least 7 days prior to treatment or lumbar puncture; patients should not take Avastin for 30 days prior to treatment 7. History of a bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or use of anticoagulants, specifically recent thrombosis or stroke in past 3 months; abnormal coagulation profile (PLT \< 100,00/μl), PT (\> 14 sec) or PTT (\> 36 sec), and INR \> 1.3 8. No more than 1 non-strategic lacune \<1.5 cm 9. Known cerebral or systemic vasculopathy 10. Significant depression and at potential risk of suicide 11. Known sensitivity/allergy to gadolinium (an alternative product may be used) and DEFINITY®. 12. Any contraindications to MRI scanning, including: 1. Large participants not fitting comfortably into the scanner 2. Difficulty lying supine and still for up to 3 hours in the MRI unit or claustrophobia 13. Any contraindication to lumbar puncture for collection of cerebral spinal fluid, including: a. Intracranial hypotension 14. Untreated, uncontrolled sleep apnea 15. Impaired renal function with estimated glomerular filtration rate \< 30 mL/min/1.73m2 or on dialysis. 16. IVIg use in the previous 6 months. 17. Live viral vaccination within the 30 days before study entry 18. Currently, or in the last 3 months participated in a clinical trial delivering an investigational product or non-approved use of a drug or device or in any other type of medical research. 19. Respiratory: chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, patients with a history of drug allergies, uncontrolled asthma or hay fever, and multiple allergies where the benefit/risk of administering DEFINITY® is considered unfavorable by the study physicians in relation to the product monograph for DEFINITY®. 20. Motor cortex atrophy deemed severe enough to limit targeting 21. Previous major allergic or anaphylactic reaction to IVIg 22. Known IgA deficiency with anti-IgA. 23. Known frontotemporal dementia; 24. Definitely or possibly pregnant (if applicable); 25. Known auto-immune condition with or without neurological manifestations (e.g., multiple sclerosis (MS), systemic lupus erythematous (SLE), Rheumatoid arthritis). 26. Current, planned or previous use of oral, intramuscular or intravenous steroid drugs (such as prednisone, prednisolone, dexamethasone, triamcinolone, methylprednisolone, oxandrolone, and others), immunosuppressant drugs (azathioprine, mycophenolate, tacrolimus, sirolimus, cyclophosphamide, and others) or NSAIDs (ibuprofen, naproxen, celecoxib, and others) in the past 30 days; 27. Other unspecified reasons that, in the opinion of the Investigator or the Sponsor, make the participant unsuitable for enrollment
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