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Table 1 Gene specific therapies approved for treatment or tested in clinical trials

From: Gene specific therapies – the next therapeutic milestone in neurology

Disease Drug name Sponsor Target or reconstituted gene Type of therapy Route of administration Mode of action Corr. to Fig. 1 Current status Trial(s)
Motoneuron disorders
SMA Nusinersen Biogen/Ionis SMN2 mRNA ASO Intrathecal Exon inclusion B Approved NCT02193074, NCT02292537
Onasemnogene abeparvovec AveXis/Novartis SMN1 gene rAAV9 Intravenous Gene reconstitution E Approved NCT03306277
Risdiplam Roche SMN2 mRNA Small molecule Oral Exon inclusion B Approval expected soon NCT02908685, NCT02913482, NCT03032172, NCT03779334
Branaplam Novartis SMN2 mRNA Small molecule Oral Exon inclusion B Phase 1/2 NCT02268552
SOD1-ALS Tofersen (BIIB067) Ionis/Biogen SOD1 mRNA ASO Intrathecal RNase H A Phase 3 NCT02623699
C9-ALS BIIB078 Ionis/Biogen C9ORF72 mRNA ASO (Mutation specific) intrathecal RNase H A Phase 2 NCT03626012
Sporadic ALS BIIB100 Biogen XPO1 mRNA ASO Intrathecal Probably RNase H A Phase 1 NCT03945279
Movement disorders
HD Tominersen (RG6042) Ionis/Roche HTT mRNA ASO intrathecal RNase H A Phase 3 NCT03761849
WVE-120101
WVE-120102
Wave Life Sciences/Takeda HTT mRNA ASO (Mutation specific) intrathecal RNase H A Phase 1/2 NCT03225833 NCT03225846
AMT-130 UniQure HTT mRNA AAV5 intrastriatal Expression of miHTT/RISC F Phase 1/2 NCT04120493
iPD VY-AADC01 Neurocrine Biosciences/ Voyager Therapeutics AADC gene AAV2 intrastriatal Gene reconstitution E Phase 1 NCT01973543
AAV-hAADC-2 Jichi Medical University AADC gene AAV2 intrastriatal Gene reconstitution E Phase 1 NCT02418598
iPD and LRKK2-PD BIIB094 Ionis/Biogen LRRK2 mRNA ASO intrathecal Probably RNase H A Phase 2 NCT03976349
GBA-PD PR001 Prevail Therapeutics GBA1 gene AAV9 gene therapy intracisternal Gene reconstitution E Phase 1/2 NCT04127578
Dementia
Sporadic AD BIIB080 Ionis/Biogen MAPTR mRNA ASO Intrathecal RNase H A Phase 1/2 NCT03186989
Muscle diseases
DMD Eteplirsen Sarepta Therapeutics Dystrophin mRNA ASO (Mutation specific) Intravenous or subcutaneous Exon 51 skipping B Approved (only FDA) NCT02255552
Golodirsen Sarepta Therapeutics Dystrophin mRNA ASO (Mutation specific) intravenous Exon 53 skipping B Approved (only FDA) NCT02500381
Multiple Sarepta therapeutics, Nippon Shinyaku (NS) Pharma, Daiichi Sankyo, Wave Life Sciences Dystrophin mRNA ASO (Mutation specific) Intravenous or subcutaneous Exon skipping of exon 45, 52 or 53 B Phases 1–3 NCT02500381, NCT04004065, NCT03675126, NCT03167255, NCT02667483, NCT03508947
Ataluren PTC Therapeutics Dystrophin mRNA Small molecule oral “Read-through”   Approved NCT01826487
Multiple Sarepta Therapeutics, Pfizer, Solid Biosciences Micro/Mini Dystrophin gene AAV intravenous Gene reconstitution E Phase 1–2 NCT03375164, NCT03769116, NCT03368742, NCT03362502, NCT03333590
LGMD2D MYO-102 Sarepta Therapeutics SGCA gene AAVrh74 intraarterial Gene reconstitution E Phase 1/2 NCT01976091
LGMD2E MYO-101/ SRP-9003 Sarepta Therapeutics SGCB gene AAVrh74 intravenous Gene reconstitution E Phase 1/2 NCT03652259
Pompe disease SPK-3006 Spark Therapeutics GAA gene rAAV9 g intravenous Gene reconstitution E Phase 1/2 NCT04093349
AAV2/8LSPhGAA Asklepios Biopharmaceutical GAA gene AAV2/8 intravenous Gene reconstitution E Phase 1/2 NCT03533673
AD-CNM and XL-CNM IONIS-DNM2–2.5Rx
(DYN101)
Ionis pharmaceuticals/ Dynacure DNM2 mRNA ASO intravenous RNase H A Phase 2 NCT04033159
XL-CNM AT132 Audentes Therapeutics MTM1 gene AAV8 intravenous Gene reconstitution E Phase 1/2 NCT03199469
Polyneuropathies
FAP Inotersen Ionis/Akcea Therapeutics TTR mRNA ASO subcutaneous RNase H A Approved NCT01737398
AKCEA-TTR-LRx Ionis/Akcea Therapeutics TTR mRNA ASO subcutaneous Probably RNase H D Phase 3 NCT04136184
Patisiran Alnylam Pharmaceuticals TTR mRNA siRNA intravenous RISC D Approved NCT01960348
Vutrisiran Alnylam Pharmaceuticals TTR mRNA siRNA subcutaneous RISC D Phase 3 NCT04153149
CTM1A scAAV1.tMCK.NTF3 Nationwide Children’s Hospital NTF3 gene scAAV1 intramuscular Gene reconstitution E Phase 1/2 NCT03520751
GAN scAAV9/JeT-GAN National Institute of Neurological Disorders and Stroke (NINDS) GAN gene scAAV9 intrathecal Gene reconstitution E Phase 1 NCT02362438
Other neurological disorders
LHON GS010 GenSight Biologics MT-ND4 gene AAV2 intravitreal Gene reconstitution E Phase 3 NCT02652780, NCT02652767, NCT03293524
Fabry disease ST-920 Sangamo Therapeutics GLA gene rAAV2/6 intravenous Gene reconstitution E Phase 1/2 NCT04046224
FLT190 Freeline Therapeutics GLA gene AAV8 intravenous Gene reconstitution E Phase 1/2 NCT04040049
CLN2 AAVrh.10CUCLN2 Weill Medical College of Cornell University CLN2 gene AAVrh.10 intracranial Gene reconstitution E Phase 1/2 NCT01414985, NCT01161576
CLN3 AT-GTX-502 Amicus Therapeutics CLN3 gene scAAV9 intrathecal Gene reconstitution E Phase 1/2 NCT03770572
CLN6 AT-GTX-501 Amicus Therapeutics CLN6 gene scAAV9 intrathecal Gene reconstitution E Phase 1/2 NCT02725580