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 |