**5.3.78 Thyreotropin releasing hormone (TRH, Protirelin)**

TRH has been tested in a larger number of clinical trials, but none of them showed a benefit in ALS patients (Brooke et al., 1986; Brooks et al., 1987; Caroscio et al., 1986; Congia et al., 1991; Hawley et al., 1987; Imoto et al., 1984; Klimek et al., 1989; Klimek et al., 1988; Miller & Warnick, 1989; Mitsumoto et al., 1986; Munsat et al., 1992; Patrignani et al., 1992; Serratrice et al., 1985; Stober et al., 1985; Thielen et al., 1987; Yamane et al., 1986).

### **5.3.79 Tilorone**

The antiviral drug tilorone did not show a benefit in ALS patients (Olson et al., 1978).

### **5.3.80 Tocopherol (Vitamin E)**

The anti-oxidant tocopherol has been evaluated in two phase II clinical trials, where tocopherol has been as add-on medication to riluzole in ALS patients. Both studies reported safe and well-tolerated drug administration, but no beneficial effect for ALS patients (Desnuelle et al., 2001; Graf et al., 2005). In a retrospective case-control study, high dosage of tocopherol decreased the risk of developing ALS (Veldink et al., 2007).

### **5.3.81 Topiramate**

Topiramate is an anti-convulsant with anti-glutamatergic effects. It has been tested in a clinical trial without benefit for ALS patients, but with an increased rate of life-threatening side effects (Cudkowicz et al., 2003).

Amyotrophic Lateral Sclerosis: An Introduction to Treatment and Trials 23

Since most clinical trials in ALS did not show a benefit for ALS patients, a number of "alternative" or off-label cures have been propagated. Besides severe ethical issues, these

Some ALS patients who are desperately looking for a relief, tend to participate in these treatments, although they have to pay large amounts of money by themselves, and no

To evaluate some of these treatments, the ALSUntangled group (www.alsuntangled.com), which is based on social networking of patients, clinicians, and scientists (Bedlack & Hardiman, 2009), reports sporadically on these treatments (see homepage for open and

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

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

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

The author has been supported by grants of the European Union within the Framework Program 7, the Germany Ministry of Research and Education (BMBF) within the National Genome Research Network NGFN-2, the German Research Foundation DFG, the intramural program of the Medical Faculty of the University of Heidelberg, the Steuben-Schurz Society,

treatments are of experimental nature, but not in the sense of a registered trial.

proven, or replicable outcome has been reported in a peer-reviewed journal.

**5.3.91 "Alternative" therapeutic approaches** 

understanding of pathophysiological aspects of MND.

completed investigations).

**6. Outlook** 

models.

clinical treatment.

**7. Abbreviations** 

ALS, amyotrophic lateral sclerosis ALSFRS, ALS functional rating scale

SOD1, [Zn, Cu] Superoxide dismutase type 1

ALSSS, ALS severity scale CNS, central nervous system FTD, Fronto-Temporal Dementia LMN, lower motor neuron MND, motor neuron disease PBP, progressive bulbar palsy PLS, primary lateral sclerosis PMA, progressive muscular atrophy ROS, Reactive oxygen species

UMN, upper motor neuron

**8. Acknowledgments** 

and the Estate of Friedrich Fischer.

### **5.3.82 Transfer factor**

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