**6. Outlook**

22 Amyotrophic Lateral Sclerosis

The antiviral agent transfer factor did not show a benefit in ALS patients (Jonas et al., 1979;

Tretinoin is the all-trans form of retinoic acid. It has various effects in the nervous system,

In a riluzole add-on phase II study (NCT00919555), tretinoin is currently evaluated in

The antimicrobial agents trypan blue and trypan red did not show a beneficial effect in ALS

VEGF is a neuroprotectice and angiogenic growth factor (Maurer et al., 2008). It is currently tested in a phase I/II clinical trial (NCT00800501) for safety and tolerability. Of note, VEGF

The calcium channel antagonist verapamil showed no beneficial effect in a clinical trail in

The 5HT1R agonist xaliproden is neurotrophic and neuroprotective. It has been evaluated in phase II/III trials, which showed modest effects on vital capacity, but not on survival of ALS

There is no drug information available for YAM80 searching literature and chemical databases. YAM80 is evaluated in a phase II study (NCT00886977) for safety and efficacy in

The antiviral drug zidovudine did not show a benefit in ALS patients (Westarp et al., 1993).

The following agents have shown promising results in preclinical assessment, but no clinical

Azathioprine, glycine, the tripeptide zVAD-fmk, AM-1241, celastrol, dantrolene, nordihydroguaiaretic acid, RO-28-2653, L-arginine, 5-hydroxytryptophan, N-acetylated alphalinked acidic dipeptidase, mechano-growth factor (MGF), hepatocyte growth factor (HGF), glial-derived neurotrophic factor (GDNF), promethazine and other anti-histaminergic drugs, calcium disodium EDTA, toluloxy propane, ammonium tetramolybdate (for details, see

(Mitsumoto, 2009; Zoccolella et al., 2007)), and cannabis (Carter et al., 2010).

including neuroprotection and neuroregeneration (for review, see (Lee et al., 2009)).

patients (Montanari & Pessina, 1955; Schwob & Bonduelle, 1952).

**5.3.85 Vascular endothelial growth factor (VEGF, sNN0029)** 

patients (Lacomblez et al., 2004; Meininger et al., 2004).

**5.3.82 Transfer factor** 

**5.3.83 Tretinoin (all-***trans* **retinoic acid)** 

combination with pioglitazone.

**5.3.84 Trypan blue and trypan red** 

must be administered into the CSF.

ALS patients (Miller et al., 1996).

**5.3.87 Xaliproden (SR57746)** 

**5.3.86 Verapamil** 

**5.3.88 YAM80** 

ALS patients.

**5.3.89 Zidovudine** 

**5.3.90 Preclinical agents** 

trials have been conducted:

Olarte et al., 1979).

ALS remains a mysterious disease with a limited life expectancy and a deteriorating condition, although efforts in basic and clinical research brought some light in the understanding of pathophysiological aspects of MND.

With dozens of failed neuropharmacological trials in ALS, the current concept of the design of clinical trials in ALS patients must be reevaluated, as well as the pre-clinical models.

Future research may concentrate on the definition of ALS, maybe by the use of biomarkers, and on translational aspects, that is, how to transfer pre-clinical results into successful clinical treatment.
