The view from here. January 2014

The first view from here of 2014 deals with aspects of the treatment of skeletal disorders, with a focus on osteoporosis

I hope that everyone enjoyed their holidays and now I guess it’s back to the grind, or excitement, depending upon your point of view. To whet your appetite for the year ahead, this newsletter concentrates upon aspects of the biology and drug discovery related to osteoporosis.

Osteoporosis is a serious disease, its incidence is increasing as we see the baby boomers entering their twilight years. The mainstay of treatment over the past 20 years has been bisphosphonates. These drugs increase bone mineral density (BMD) by inhibition of osteoclasts, hence reducing bone resorption. Although these agents do not produce an increase in new bone formation, the inhibition of bone resorption can produce increases in BMD in the order of 3%per year. This results in a significant reduction in fracture incidence, but there is still a large residual risk. Fractures in the elderly represent a significant clinical issue, there is the cost in hospitalization of an elderly patient, not including social aspects of their mobility upon discharge and impact on care in the home. There is, of course, a significant risk of mortality following hip surgery. It is estimated that 25% of patients die within 1 year after fracture; common causes of death include infection, pneumonia or fat embolus. Therefore agents capable of maintaining (or increasing) BMD will have significant effects upon lifestyle in the elderly and, potentially, have a great health economic impact.
The free downloads available in this newsletter highlight some of the most recent developments in osteoporosis treatments. I will elaborate on them below.
The first article highlights an ingenious approach to the discovery of a new agent for the treatment of osteoporosis. The article, entitled: “Sclerostin: how human mutations have helped reveal a new target for the treatment of osteoporosis” by Martyn K. Robinson, John Caminisand Mary E. Brunkow, shows how the observation that an Afrikaaner population presenting with the rare disease, sclerosteosis (which is almost unknown outside of South Africa) could trigger research that could lead to a new drug. The disease, which produces a monogenic high bone mass disorder became the focus of research, which resulted in the observation that the elevated bone mass was as a result of a defective gene encoding a regulator of bone formation. This paper outlines aspects of the biology of the disorder and how the authors capitalized on the findings to develop a potential therapy.
The second article, by Marietta Kaszkin-Bettag, entitled: “Is autologous chondrocyte implantation (ACI) an adequate treatment option for repair of cartilage defects in paediatric patients?” This deals more with the clinical aspects of cellular implantation in children. One does not always associate cartilage defects with children, much more with traumatic injury or in the elderly, but it is actually a common disorder. Left untreated, or inadequately treated, there are significant issues with reduced mobility, pain and the potential that the individuals may go on to develop premature osteoarthritis for example. Poor treatment will give a poor prognosis for future mobility and represent a significant morbidity and cost to health providers. The article discusses the relative benefits of various procedures and overviews outcomes of the approaches.
Last, but by no means least, is the review from T. Ponnapakkam, R. Katikaneni, J. Sakon, R. Stratfordand R.C. Gensure, entitled: “Treating osteoporosis by targeting parathyroid hormone to bone”. This article discusses the synergistic effects one can have on bone by combining an anabolic agent, parathyroid hormone, with anti-resorptive agents (bisphosphonates). Moreover, they discussed the benefit that might be obtained by targeting the hormone using a collagen-binding domain, with respect to reducing side effects (in particular hypercalcaemia and tumour risk). They highlight the benefits from using targeted versions of currently available drugs used in synergy in the treatment of this disabling disorder.
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. He has authored over 40 peer-reviewed articles, written several book chapters and has held a number of patents.

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