Motor Nöron Hastalıklarında Güncel Tedavi Yaklaşımları
Özet
Motor nöron hastalıkları, üst ve alt motor nöronların progresif dejenerasyonu ile seyreden nörodejeneratif hastalıklardır. Amyotrofik lateral skleroz (ALS) ve spinal musküler atrofi (SMA) başta olmak üzere, bu hastalıklarda uygulanan güncel hastalık modifiye edici ve semptomatik tedavi yaklaşımları güncel klinik veriler ışığında ele alınmaktadır. ALS’de riluzol ve edaravon gibi standart tedavilere ek olarak, SOD1 mutasyonuna yönelik antisens oligonükleotid tedavisi olan tofersen ve deneysel ajanlar özetlenmektedir. SMA’da ise nusinersen, onasemnogene abeparvovec ve risdiplam gibi genetik temelli tedavilerin etki mekanizmaları ve klinik sonuçları değerlendirilmektedir. Ayrıca rehabilitasyon, solunum ve beslenme desteğinin hastalık yönetimindeki önemi vurgulanmaktadır.
Referanslar
Kiernan MC, Vucic S, Cheah BC, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377(9769):942-955. doi:10.1016/S0140-6736(10)61156-7
Fang T, Al Khleifat A, Meurgey JH, et al. Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study. Lancet Neurol. 2018;17(5):416-422. doi:10.1016/S1474-4422(18)30054-1
Writing Group; Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(7):505-512. doi:10.1016/S1474-4422(17)30115-1
Rothstein J, Genge A, De Silva S, et al. Efficacy and Safety of Once Daily Dosing vs. Approved On/Off Dosing of Edaravone Oral Suspension Up to 48 Weeks in Patients With Amyotrophic Lateral Sclerosis (Study MT-1186-A02). Muscle Nerve. 2025;72(3):433-442. doi:10.1002/mus.28448
Miller TM, Cudkowicz ME, Genge A, et al. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2022;387(12):1099-1110. doi:10.1056/NEJMoa2204705
Miller T, Cudkowicz M, Shaw PJ, et al. Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020;383(2):109-119. doi:10.1056/NEJMoa2003715
.Paganoni S, Macklin EA, Hendrix S, et al. Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis. N Engl J Med. 2020;383(10):919-930. doi:10.1056/NEJMoa1916945
Alqallaf A, Cates DW, Render KP, Patel KA. Sodium Phenylbutyrate and Taurursodiol: A New Therapeutic Option for the Treatment of Amyotrophic Lateral Sclerosis. Ann Pharmacother. 2024;58(2):165-173. doi:10.1177/10600280231172802
Paganoni S, Fournier CN, Macklin EA, et al. Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(2):e2459058. Published 2025 Feb 3. doi:10.1001/jamanetworkopen.2024.59058
Writing Committee for the HEALEY ALS Platform Trial, Andrews J, Paganoni S, et al. Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial. JAMA Neurol. 2025;82(4):333-343. doi:10.1001/jamaneurol.2024.5249
Wakita H, Tomimoto H, Akiguchi I, et al. Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat. Brain Res. 2003;992(1):53-59. doi:10.1016/j.brainres.2003.08.028
Cudkowicz M, Genge A, Maragakis N, et al. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2021;20(10):821-831. doi:10.1016/S1474-4422(21)00242-8
Shefner JM, Andrews JA, Genge A, et al. A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2021;22(3-4):287-299. doi:10.1080/21678421.2020.1822410
Mora JS, Genge A, Chio A, et al. Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial [published correction appears in Amyotroph Lateral Scler Frontotemporal Degener. 2024 Feb;25(1-2):223. doi: 10.1080/21678421.2023.2273111.]. Amyotroph Lateral Scler Frontotemporal Degener. 2020;21(1-2):5-14. doi:10.1080/21678421.2019.1632346
Cudkowicz ME, Lindborg SR, Goyal NA, et al. A randomized placebo-controlled phase 3 study of mesenchymal stem cells induced to secrete high levels of neurotrophic factors in amyotrophic lateral sclerosis. Muscle Nerve. 2022;65(3):291-302. doi:10.1002/mus.27472
Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155-165. doi:10.1016/0092-8674(95)90460-3
Wadman RI, van der Pol WL, Bosboom WM, et al. Drug treatment for spinal muscular atrophy types II and III. Cochrane Database Syst Rev. 2020;1(1):CD006282. Published 2020 Jan 6. doi:10.1002/14651858.CD006282.pub5
