Reviews & Analysis

The first-in-human phase I trial of stem cell transplantation for amyotrophic lateral sclerosis was approved by the FDA in 2009 and is ongoing. In their Perspectives article, Eva Feldman and colleagues, who are conducting the trial, discuss the preclinical research supporting this therapeutic approach, key aspects of the trial design to overcome translational issues, and ongoing challenges to address in future studies.

Clinical trials for amyotrophic lateral sclerosis have failed to yield a single new drug over the past 17 years. In their Opinion article, Gordon and Meininger provide insights into possible reasons for the lack of success, such as the heterogeneity of the disease, limitations of preclinical models, and the choice of clinical end points. They also present possible strategies to address the ongoing challenges, including appropriate dose selection and development of suitable biomarkers.

Many individuals with Parkinson disease (PD) adopt a sedentary lifestyle as a result of the motor and nonmotor complications associated with the disease. In this article, Speelman et al. discuss 10 reasons why exercise may be of benefit to patients with PD, suggesting that increased levels of physical activity can have disease-specific and, potentially, disease-modifying effects. The limitations and obstacles to changing the sedentary lifestyles of patients with PD are also discussed.

The considerable need for research on Alzheimer disease (AD) is complicated by the impaired capacity of patients with AD to provide informed consent to participate in research and the lack of well-defined policy guidelines on this issue. Scott Kim highlights the importance of distinguishing between capacity and authenticity when assessing the ability of a patient with AD to provide informed consent, and discusses how the role of surrogate decision-makers could be enhanced in this context.

Multiple system atrophy is characterized by a combination of parkinsonian, cerebellar, autonomic and pyramidal features, but recent data indicate that the clinical spectrum also includes nonmotor symptoms such as urinary disorders and orthostatic hypotension. Colosimo argues that neurologists and other specialists should be made aware that this neurodegenerative disease can manifest with nonmotor symptoms long before patients develop any overt motor disorder.

Labate et al. argue that benign mesial temporal lobe epilepsy (bMTLE)—defined as at least 24 months of seizure freedom with or without antiepileptic medication—has been under-recognized because of a bias in the literature towards refractory forms of epilepsy. Here, the authors discuss emerging concepts on bMTLE, some of which were formulated during an international workshop held in Italy.