Gene Therapy: A Potential Approach for Cancer Pain

Chronic pain is experienced by as many as 90% of cancer patients at some point during the disease. This pain can be directly cancer related or arise from a sensory neuropathy related to chemotherapy. Major pharmacological agents used to treat cancer pain often lack anatomical specificity and can have off-target effects that create new sources of suffering. These concerns establish a need for improved cancer pain management. Gene therapy is emerging as an exciting prospect. This paper discusses the potential for viral vector-based treatment of cancer pain. It describes studies involving vector delivery of transgenes to laboratory pain models to modulate the nociceptive cascade. It also discusses clinical investigations aimed at regulating pain in cancer patients. Considering the prevalence of pain among cancer patients and the growing potential of gene therapy, these studies could set the stage for a new class of medicines that selectively disrupt nociceptive signaling with limited off-target effects

Pain in Amyotrophic Lateral Sclerosis: A Neglected Aspect of Disease

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive loss of motor neurons, muscle wasting, and respiratory dysfunction. With disease progression, secondary symptoms arise creating new problematic conditions for ALS patients. Amongst these is pain. Although not a primary consequence of disease, pain occurs in a substantial number of individuals. Yet, studies investigating its pathomechanistic properties in the ALS patient are lacking. Therefore, more exploratory efforts into its scope, severity, impact, and treatment should be initiated. Several studies investigating the use of Clostridial neurotoxins for the reduction of pain in ALS patients suggest the potential for a neural specific approach involving focal drug delivery. Gene therapy represents a way to accomplish this. Therefore, the use of viral vectors to express transgenes that modulate the nociceptive cascade could prove to be an effective way to achieve meaningful benefit in conditions of pain in ALS

Wiselib: A Generic Algorithm Library for Heterogeneous Sensor Networks

One unfortunate consequence of the success story of wireless sensor networks (WSNs) in separate research communities is an ever-growing gap between theory and practice. Even though there is a increasing number of algorithmic methods for WSNs, the vast majority has never been tried in practice; conversely, many practical challenges are still awaiting efficient algorithmic solutions. The main cause for this discrepancy is the fact that programming sensor nodes still happens at a very technical level. We remedy the situation by introducing Wiselib, our algorithm library that allows for simple implementations of algorithms onto a large variety of hardware and software. This is achieved by employing advanced C++ techniques such as templates and inline functions, allowing to write generic code that is resolved and bound at compile time, resulting in virtually no memory or computation overhead at run time. The Wiselib runs on different host operating systems, such as Contiki, iSense OS, and ScatterWeb. Furthermore, it runs on virtual nodes simulated by Shawn. For any algorithm, the Wiselib provides data structures that suit the specific properties of the target platform. Algorithm code does not contain any platform-specific specializations, allowing a single implementation to run natively on heterogeneous networks. In this paper, we describe the building blocks of the Wiselib, and analyze the overhead. We demonstrate the effectiveness of our approach by showing how routing algorithms can be implemented. We also report on results from experiments with real sensor-node hardware.Comment: 16 pages, 1 figure, 7 tables. Appears in European Conference on Wireless Sensor Networks (EWSN 2010

Progress in gene therapy for neurological disorders

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy

A Conditioning Lesion Provides Selective Protection in a Rat Model of Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is neurodegenerative disease characterized by muscle weakness and atrophy due to progressive motoneuron loss. The death of motoneuron is preceded by the failure of neuromuscular junctions (NMJs) and axonal retraction. Thus, to develop an effective ALS therapy you must simultaneously preserve motoneuron somas, motor axons and NMJs. A conditioning lesion has the potential to accomplish this since it has been shown to enhance neuronal survival and recovery from trauma in a variety of contexts. rats that received a conditioning lesion was delayed and less severe. These improvements in motor function corresponded to greater motoneuron survival, reduced motor axonopathy, and enhanced NMJ maintenance at disease end-stage. Furthermore, the increased NMJ maintenance was selective for muscle compartments innervated by the most resilient (slow) motoneuron subtypes, but was absent in muscle compartments innervated by the most vulnerable (fast fatigable) motoneuron subtypes.These findings support the development of strategies aimed at mimicking the conditioning lesion effect to treat ALS as well as underlined the importance of considering the heterogeneity of motoneuron sub-types when evaluating prospective ALS therapeutics

The use of preoperative radiotherapy in the management of patients with clinically resectable rectal cancer: a practice guideline

BACKGROUND: This systematic review with meta-analysis was designed to evaluate the literature and to develop recommendations regarding the use of preoperative radiotherapy in the management of patients with resectable rectal cancer. METHODS: The MEDLINE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings of the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were systematically searched for evidence. Relevant reports were reviewed by four members of the Gastrointestinal Cancer Disease Site Group and the references from these reports were searched for additional trials. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Two meta-analyses of preoperative radiotherapy versus surgery alone, nineteen trials that compared preoperative radiotherapy plus surgery to surgery alone, and five trials that compared preoperative radiotherapy to alternative treatments were obtained. Randomized trials demonstrate that preoperative radiotherapy followed by surgery is significantly more effective than surgery alone in preventing local recurrence in patients with resectable rectal cancer and it may also improve survival. A single trial, using surgery with total mesorectal excision, has shown similar benefits in local recurrence. CONCLUSION: For adult patients with clinically resectable rectal cancer we conclude that: • Preoperative radiotherapy is an acceptable alternative to the previous practice of postoperative radiotherapy for patients with stage II and III resectable rectal cancer; • Both preoperative and postoperative radiotherapy decrease local recurrence but neither improves survival as much as postoperative radiotherapy combined with chemotherapy. Therefore, if preoperative radiotherapy is used, chemotherapy should be added postoperatively to at least patients with stage III disease

An efficient MAC-based scheme against pollution attacks in XOR network coding-enabled WBANs for remote patient monitoring systems

Wireless Body Area Networks (WBANs) play a pivotal role to remote patient monitoring which is one of the main applications of m-Health. However, WBANs comprise a subset of Wireless Sensor Networks (WSNs), and thus, they inherit the limitations of WSNs in terms of communication bandwidth, reliability and power consumption that should be addressed so that WBANs can reach their full potential. Towards this direction, XOR Network Coding (NC) is a promising solution for WBANs. Nevertheless, XOR NC is vulnerable to pollution attacks, where adversaries (i.e., compromised intermediate nodes) inject into the network corrupted packets that prevent the destination nodes from decoding correctly. This has as a result not only network resource waste but also energy waste at the intermediate nodes. In this sense, pollution attacks comprise a serious threat against WBANs (i.e., resource-constrained wireless networks), that should be addressed so that WBANs can reap the benefits of XOR NC. Therefore, in this paper, we propose an efficient Message Authentication Code (MAC)-based scheme providing resistance against pollution attacks in XOR NC-enabled WBANs for remote patient monitoring systems. Our proposed scheme makes use of a number of MACs which are appended to the end of each native packet. Our results show that the proposed MAC-based scheme is more efficient compared to other competitive schemes for securing XOR NC against pollution attacks in resource-constrained wireless networks, in terms of communication bandwidth and computational complexity

Progress in gene therapy for neurological disorders

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy