The September issue of Drug Discovery Today, Editor’s Choice features a series of articles with a focus on Neurology. The scope of therapeutics for neurological disorders is wide and highly diverse and has been a major focus for Pharmaceutical company activity, virtually since its inception. There have been many notable successes, however, the treatment of neurological disorders still represents a significant unmet medical need. One of the more significant areas in neurology is seizure, of which epilepsy retains the lion’s share of research interest and money. More recently, there has been increasing interest and spend in treatments for Alzheimer’s disease and recent news suggests that perhaps one might be cautiously optimistic of developments in this area. The focus of this newsletter is on developments in the field of Amyotrophic Lateral Sclerosis (ALS) and an analysis of FDA-approved drugs for neurological disorders over the past 80 years. As the population becomes ever more proportionally aged, neurologic targeted drugs will become much more valuable both to patient and the industry as a whole.
The first article of this month’s trilogy, is by Pascaline Clerc, Scott Lipnick and Catherine Willett, of the The Humane Society of the United States, Gaithersburg, USA and Massachusetts General Hospital, Harvard Medical School, Boston, USA entitled: “A look into the future of ALS research”. The authors discuss the (as yet incomplete) pathobiology of the disorder and the relative lack of success in the development of drugs. The only compound to go through the process and be approved has been riluzole, whose benefit to the patient is somewhat limited. The article continues to focus upon animal models of the disorder and their relative utility and how they are generally ineffective for the translation of compounds to the clinic.
The second featured article, by Yongjin Zhu, Anastasios Fotinos, Lilly L.J. Mao, Nazem Atassi, Edward W. Zhou, Sarfraz Ahmad, Yingjun Guan, James D. Berry, Merit E. Cudkowicz and Xin Wang of Harvard Medical School, USA, Aimcan, Canada and Weifang Medical University, China is entitled: “Neuroprotective agents target molecular mechanisms of disease in ALS”. They discuss current approaches that have resulted in neuroprotective compounds capable of reducing bodyweight loss in animal models. They discuss such agents with respect to their abilities with respect to bodyweight loss, muscle damage, disease onset and survival. From this, structure-activity relationships can be derived and the authors intend to propose screening strategies for novel compounds based upon such observations.
Finally, is the article from Michael S. Kinch, then of Yale University, USA entitled: “An analysis of FDA-approved drugs for neurological disorders”. He critically analyses the submission and approval of drugs for neurological disorders, from the 1930s to the current day. He demonstrates a relatively low, yet constant rate of approval with peaks of activity in the 1950s and 1990s. It is clear that the initial submissions and approvals were in the absence of mechanistic understanding and largely achieved from the use of phenotypic assays. The author makes the tantalizing comment that perhaps we might be more successful in the future to move back to a more classical pharmacology approach. This comment is particularly tantalizing in view of the comments from the first article in this newsletter. Food for thought, perhaps.
Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents.