**5.3.31 Glatiramer acetate**

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, stimulates anti-glutamatergic growth factor effects.

In a phase II clinical trial (NCT00326625), glatiramer acetate has not shown any beneficial effect in ALS patients (Meininger et al., 2009).

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

G-CSF is a hematopoietic growth and maturation factor with neuroprotective and neuroregenerative effects (reviewed in Maurer et al., 2008).

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 down disease progression.

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

Human growth hormone (hGH) stimulates the production and release of insulin-like growth factor I (IGF-1) which induces cell proliferation and differentiation (Rosenbloom, 2009).

GH has evaluated in a phase II trial (NCT00635960) with no effects on disease progression (Sacca et al., 2011).

Amyotrophic Lateral Sclerosis: An Introduction to Treatment and Trials 17

It has been tested in a phase II study in combination with testosterone (NCT00004771), the

Levamisole is a synthetic imidazothiazole derivative with anti-helmintic and immunomodulatory effects. In a clinical trial, no beneficial effects have been seen for ALS

Lithium has been described as inductor of autophagy and anti-oxidant. Clinically, it is used

In a phase II study (EudraCT ), lithium did not show efficacy with regard to survival and

In another phase II study, lithium was reported to delay disease progression (Fornai et al., 2008), but in a follow-up, riluzole add-on phase II study (NCT00818389), lithium has been proven to be safe and well tolerated in ALS patients, but did not slow disease progression (Aggarwal et al.). Due to these findings, two other studies of lithium are currently not

Memantine non-competitive antagonist at the NMDA and AMPA glutamate receptors with

In two phase II/III clinical trials (NCT01020331, NCT00409721), memantine was safe and

Methylcobalamin is an analog of vitamin B12, which reduces the concentration of homocystein, an excitatory amino acid which showed toxic effects on motor neurons by inducing apoptosis. ALS patients treated with high doses of methylcobalamin (MeCbl) showed an increase in compound muscle action potential amplitudes (CMAPs) after 4 weeks of treatment (Kaji et al., 1998). It increased the decline in ALS patients with regard to becoming respirator-bound

Methylcobalamin is currently evaluated in two phase III studies (NCT00445172,

In a phase III study (NCT00047723), minocycline showed harmful effects of minocycline in

Modafinil is a psychostimulant clinically used for the treatment of narcolepsy and other

Minocycline has been described as anti-apoptotic and anti-inflammatory.

tolerated, but no efficacy has been found in ALS patients (de Carvalho et al., 2010).

**5.3.43 Leuprorelin (Leuprolide)** 

patients (Olarte & Shafer, 1985).

keeping of patient autonomy (Chio et al.).

recruiting patients (NCT00925847, NCT00790582).

**5.3.47 Methylcobalamin (E0302, mecobalamin)** 

results are awaited.

**5.3.44 Levamisole** 

**5.3.45 Lithium** 

as mood stabilizer.

**5.3.46 Memantine** 

(Izumi & Kaji, 2007).

**5.3.48 Minocycline** 

**5.3.49 Modafinil** 

sleep disorders.

NCT00444613) in ALS patients

ALS patients (Gordon et al., 2007).

low affinity.

Leuprorelin is a is a nonapeptide and a GnRH analog.
