Table 2.
Examples of families of compounds that have been investigated (or are being presently investigated) for their potential disease‐modifying properties in neurodegenerative disorders and that reached clinical testing
| Type of compounds classified according to their major mechanism of action | Disease | Result in clinical testing | |
|---|---|---|---|
| Antiexcitotoxic agents | Ceftriaxone | ALS | Failed |
| Riluzole | ALS | Approved for the first time in 1995 | |
| Riluzole | AD | Under investigation | |
| Riluzole | PD | Failed | |
| Talampanel | ALS | Failed | |
| Memantine | AD | Approved for the first time in 1989a | |
| Memantine | ALS | Failed | |
| Memantine | HD | Under investigation | |
| Antioxidant agents | Coenzyme Q10 | ALS, PD, HD | Failed |
| Creatine | ALS, PD | Failed | |
| Edavarone | ALS | Approved in 2015 in Japan | |
| Benfotiamine | AD | Under investigation | |
| Vitamin E | PD | Failed | |
| Anti‐inflammatory agents | Celecoxib | ALS | Failed |
| Glatiramer acetate | ALS | Failed | |
| Minocycline | ALS, PD | Failed | |
| Pioglitazone | ALS | Failed | |
| Pioglitazoneb | AD | Under investigation | |
| Rosiglitazoneb | AD | Failed | |
| Masitinib | ALS | Approved as orphan drug in 2015 | |
| Mitochondria‐targeted agents | Olexisome | ALS | Failed |
| SBT‐020 | HD | Under investigation | |
| Dexpramipexole | ALS | Failed | |
| Latrepirdine | AD | Failed | |
| Neurotrophic factors | BDNF | ALS | Failed |
| IGF‐1 | ALS | Failed | |
| CNTF | ALS | Failed | |
| NGF | AD | Failed | |
| GDNF | PD | Failed | |
| Neurturin | PD | Failed | |
| Autophagy enhancers | Trehalose | HD | Under investigation |
| Apoptosis inhibitors | THC 346 and CEPI 347 | PD | Failed |
| Cholinergic agents | Donepezil | AD | Approved for the first time in 1997a |
| Rivastigmine | AD | Approved for the first time in 2000a | |
| Galantamine | AD | Approved for the first time in 2001a | |
| Protein (β‐amyloid, tau, huntingtin, α‐synuclein, LRRK‐2)‐targeted agents | Immunotherapy (solanezumab) | AD | Failed |
| Immunotherapy (crenezumab) | AD | Under investigation | |
| β‐Secretase inhibitors (AZD3293) | AD | Under investigation | |
| γ‐Secretase inhibitors (semagacestat) | AD | Failed | |
| Inhibitors βA aggregation (tramiprosate) | AD | Failed | |
| Htt‐lowering ASO (ISIS‐443139) | HD | Under investigation | |
| tau inhibitor (methylene blue) | AD | Under investigation | |
| Inhibitors of GSK‐3β (tideglusib) | AD | Failed | |
| SNCA agents (NPT200‐11; nilotinib) | PD | Under investigation | |
| LRRK‐2 inhibitors (DNL 201) | PD | Under investigation | |
| Others (different mechanisms of action) | Lithium | ALS, AD | Failed |
| Valproate | ALS, AD | Failed | |
| Statins | AD | Failed | |
| Rasagiline | AD | Under investigation | |
| Rasagiline | PD | Failed | |
| Ambroxol | PD | Under investigation | |
| Laquinimod | HD | Under investigation | |
| Pridopidine | HD | Failed | |
| PF‐0254920 | HD | Failed | |
a
Symptom‐relieving agents with potential neuroprotective properties.
b
Can also promote β‐secretase inhibition.
βA, β‐amyloid; ASO, antisense oligonucleotides; BDNF, brain‐derived neurotrophic factor; CNTF, ciliary neurotrophic factor; GDNF, glial cell‐derived neurotrophic factor; GSK‐3β, glycogen synthase kinase‐3β; Htt, huntingtin; IGF‐1, insulin‐like growth factor 1; LRRK‐2, leucine‐rich repeat kinase‐2; NGF, nerve growth factor; SNCA, α‐synuclein.