Chin Med J (Taipei) 1998;61:S154.

ALS: New Hope for Therapy

Michael Swash

Department of Neurology, St Bartholomew's and the Royal London Hospital. School of Medicine. London E1 1BB, UK

Abstract

The history of ALS research includes clinical trials of various possible therapies from soon after Charcot's description of the disease in 1874. In recent times trials have moved from open-label, unblinded experiments to formal double-blind, placebo-controlled designs. The latter have become large and expensive, seeking to demonstrate efficacy in relation to a number of end-points. Typically, a modern trial would involve end-points such as death, but would also utilise measurements of strength, or of forced vital capacity. Further data collection now commonly utilises techniques derived from cancer trials, in which quality of life (QoL) data are collected porspectively in an effort to demonstrate a meaningful effect on social and personal aspects of patients' well-being during the study. Indeed, a beneficial effect on QoL in the treated group is regarded as an end-point sufficient to be used in applications for licensing of the product.

These approaches have resulted in trials becoming very large and complex. This result implies that the sensitivity of the measures used is low, or that the therapeutic effect sought in these trials is relatively small. These disappointing comments arise from the continuing lack of understanding of the basic pathophysiology of the disease. More thorough understanding of the causative mechanisms would lead to more effective therapies, or preventive strategies and, certainly, to derivation of a biological measure of disease progression. The latter would transform ALS research.

These concepts will be discussed in relation to data from recent clinical trials, and information from current research on the pathogenesis of ALS. It seems probable that research into this disease is at a critical point, and that future research will be much more closely focused and that an era of rapid advance is beginning.

[Chin Med J (Taipei) 1998;61:S154.]