**5.3.28 Escitalopram**

14 Amyotrophic Lateral Sclerosis

Creatine supplementation temporarily increased maximal isometric power in ALS patients

In a phase I dose-escalation trial, creatine concentrations in the brain increased after oral

Currently, creatine is evaluated in a phase II clinical trial (NCT01257581) in combination

The immunosuppressant cyclophosphamide showed only a temporary amelioration of

Dexpramipexole is a synthetic amino-benzothiazole and the (+)-enantiomer of pramipexole which has dopaminergic activity and is a mitochondrial neuroprotectant by scavenging reactive oxygen and nitrogen species (RONS) (Cheah & Kiernan, 2010; Gribkoff & Bozik,

In earlier studies, RPPX reduced oxidative stress in sporadic ALS patients (Pattee et al., 2003). RPPX has been found to be safe and tolerable (Bozik et al., 2010; Wang et al., 2008), but did not change ALSFRS-R (NCT00140218, NCT00600873, NCT00596115, NCT00647296) (Wang et al., 2008). In the open-label extension protocol, RPPX caused a non-significant reduction in the slope of decline in the ALSFRS-R score (NCT00931944)

The potassium channel blocker DAP did not show a benefit in ALS patients (Aisen et al., 1996; Aisen et al., 1995). Currently, the drug is re-evaluated after a phase I safety study

It has been tested in a phase II study (NCT00812851) in ALS patients suffering from muscular cramps, where no subjective improvement of cramp intensity has been seen

It has been tested in several phase II/III clinical trials (NCT00330681, NCT00415519, NCT00424463) for safety and efficacy. A phase II study found a possible delay in the progression of functional motor symptoms in ALS patients (Yoshino & Kimura, 2006).

EPO is a hematopoietic growth factor with neuroprotective properties (Maurer et al., 2008).

It has been evaluated in a phase II trial, finding no effects on survival and functional

symptoms in ALS patients without a long-term benefit (Gourie-Devi et al., 1997).

RPPX is currently evaluated in a phase III study (NCT01281189) in ALS patients.

Dronabinol is a synthetic Δ9-tetrahydrocannabinol (Delta-9-THC, Δ9-THC, THC).

Edavarone is an anti-oxidant free radical scavenger (Takahashi, 2009).

Moreover, EPO exhibited anti-inflammatory and anti-apoptotic effects.

**5.3.23 Dexpramipexole (R-(+) pramipexole; RPPX; KNS-760704)** 

(Mazzini et al., 2001).

administration (Atassi et al., 2010).

with tamoxifen in ALS patients.

**5.3.22 Cyclophosphamide** 

2008).

(Wang et al., 2008).

(Bertorini et al., 2011).

**5.3.25 Dronabinol** 

(Weber et al., 2010).

**5.3.24 3,4-Diaminopyridine (DAP)** 

**5.3.26 Edaravone (MCI-186; NSC 2629)** 

**5.3.27 Erythropoietin (EPO)** 

outcome (Lauria et al., 2009).

Escitalopram is a selective serotonin reuptake inhibitor (SSRI) and used clinically as an antidepressant.

It has been tested in a phase III clinical trial (NCT00965497) for the improvement of depressive symptoms and the quality of life in ALS patients.

### **5.3.29 Gabapentin**

Gabapentin is an anti-convulsant with anti-glutamatergic effects, which have been proposed to slow down neuronal pathology (Welty et al., 1995).

It has been tested in a phase II trial finding a smaller slope in arm strength decrase (Miller et al., 1996), but a subsequent phase III trial has not shown beneficial effects of (Miller et al., 2001). No effects on neuronal integrity have been found in an MR spectroscopy study (Kalra et al., 2003).

### **5.3.30 Gangliosides**

Gangliosides are derivatives of sialylated glycosphingolipids containing one to five sialic acids at various anomeric linkage sites to the core glycan. They modulate the effect of nerve growth factor and activate protein kinase (DeFelice & Ellenberg, 1984; Rapport, 1990).

Gangliosides have been tested in several clinical trials without benefit for ALS patients (Bradley et al., 1984; Harrington et al., 1984; Lacomblez et al., 1989).
