Amyotrophic lateral sclerosis (ALS) is an extremely heterogeneous disease of motor neurons that eventually leads to death. Despite impressive advances in understanding the genetic, molecular, and pathological mechanisms of the disease, the only drug approved to date by both the FDA and EMA is riluzole, with a modest effect on survival. In this opinion view paper, we will discuss how to address some challenges for drug development in ALS at the conceptual, technological, and methodological levels. In addition, socioeconomic and ethical issues related to the legitimate need of patients to benefit quickly from new treatments will also be addressed. In conclusion, this brief review takes a more optimistic view, given the recent approval of two new drugs in some countries and the development of targeted gene therapies.

Spinal cord stimulation (SCS) is an approved treatment for intractable pain and has recently emerged as a promising area of research for restoring function after spinal cord lesion. This review will focus on the historical evolution of this transition and the path that remains to be taken for these methods to be rigorously evaluated for application in clinical practice. New developments in SCS are being driven by advances in the understanding of spinal cord lesions at the molecular, cellular, and neuronal levels, as well as the understanding of compensatory mechanisms. Advances in neuroengineering and the computational neurosciences have enabled the development of new conceptual SCS strategies, such as spatiotemporal neuromodulation, which allows spatially selective stimulation at precise time points during anticipated movement. It has also become increasingly clear that these methods are only effective when combined with intensive rehabilitation techniques, such as new task-oriented methods and robotic aids. The emergence of innovative approaches to spinal cord neuromodulation has sparked significant enthusiasm among patients and in the media. Non-invasive methods are perceived to offer improved safety, patient acceptance, and cost-effectiveness. There is an immediate need for well-designed clinical trials involving consumer or advocacy groups to evaluate and compare the effectiveness of various treatment modalities, assess safety considerations, and establish outcome priorities.