**5.3.19 CK-2017357**

With regard to the loss of skeletal muscle strength, the substituted urea derivative CK-2017357 is claimed to activate the muscle protein troponin in fast skeletal muscle fibres. A proposed mode-of-action is sensitizing the sarcomere to calcium, thus the neuro-muscular transmission is amplified, thus muscle power increases and the time to musclular fatigue is delayed (von Haehling et al., 2010).

A phase IIa study (NCT01089010) was completed in 2010 and showed a trend towards short-term improvements in grip-strength and respiration parameters.

### **5.3.20 Coenzyme Q10**

Coenzyme Q10 has been proposed to inhibit neurodegeneration. In a phase II clinical trial, it was well tolerated and safe (Ferrante et al., 2005), but showed no efficacy in a phase II futility trial (NCT00243932) (Kaufmann et al., 2009; Levy et al., 2006).

### **5.3.21 Creatine**

Creatine acts as anti-oxidant and is a mitochondrial co-factor.

It has been evaluated in several phase II clinical trials (NCT00070993, NCT00005674, NCT00005766) which reported no beneficial effect in ALS patients (Groeneveld et al., 2003; Shefner et al., 2004), as well as a phase III clinical trial (NCT00069186) (Rosenfeld et al., 2008).

Amyotrophic Lateral Sclerosis: An Introduction to Treatment and Trials 15

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

It has been tested in a phase III clinical trial (NCT00965497) for the improvement of

Gabapentin is an anti-convulsant with anti-glutamatergic effects, which have been proposed

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

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

Glatiramer acetate is a random polymer composed of four amino acids that are found in myelin basic protein (MBP). It has been proposed that it inhibits neuroinflammation,

In a phase II clinical trial (NCT00326625), glatiramer acetate has not shown any beneficial

G-CSF is a hematopoietic growth and maturation factor with neuroprotective and

G-CSF has been evaluated in a phase II study (NCT00298597) in ALS patients, finding no differences with regard to functional outcome between study groups, but slowing the progression of white matter tract destruction (Duning et al., 2011). In a second phase II trial (NCT00397423), the authors reported preliminary data on 13 patients with slower disease progression (Zhang et al., 2009). Another clinical trial did not report statistically significant differences between study and control group (Nefussy et al.), but a trend towards slowing

Human growth hormone (hGH) stimulates the production and release of insulin-like growth factor I (IGF-1) which induces cell proliferation and differentiation (Rosenbloom,

GH has evaluated in a phase II trial (NCT00635960) with no effects on disease progression

depressive symptoms and the quality of life in ALS patients.

(Bradley et al., 1984; Harrington et al., 1984; Lacomblez et al., 1989).

**5.3.32 Granulocyte colony stimulating Factor (G-CSF; AX200)** 

neuroregenerative effects (reviewed in Maurer et al., 2008).

to slow down neuronal pathology (Welty et al., 1995).

stimulates anti-glutamatergic growth factor effects.

effect in ALS patients (Meininger et al., 2009).

**5.3.33 Growth hormone (GH, Somatropin)** 

**5.3.28 Escitalopram** 

**5.3.29 Gabapentin** 

**5.3.30 Gangliosides** 

**5.3.31 Glatiramer acetate** 

down disease progression.

2009).

(Sacca et al., 2011).

et al., 2003).

antidepressant.

Creatine supplementation temporarily increased maximal isometric power in ALS patients (Mazzini et al., 2001).

In a phase I dose-escalation trial, creatine concentrations in the brain increased after oral administration (Atassi et al., 2010).

Currently, creatine is evaluated in a phase II clinical trial (NCT01257581) in combination with tamoxifen in ALS patients.
