Prerequisites for the pharmaceutical industry to develop and commercialise helminths and helminth-derived product therapy

During the past 10 years, immunologists, epidemiologists and parasitologists have made many new exciting discoveries in the field of helminth-mediated immune regulation. In addition, many animal experiments have shown that certain helminths or products derived from helminths can protect mice from developing allergic or autoimmune disease. Some clinical trials utilising Trichuris suis or Necator americanus for the treatment of allergic disorders and inflammatory bowel disease have been conducted. The outcomes of these trials suggest that they may be used to treat these disorders. However, to date no helminth therapy is routinely being applied to patients and no helminth-derived product therapy has been developed. In order to bring new drugs to the market and shoulder the enormous costs involved in developing such therapies, pharmaceutical companies need to be involved. However, currently the resources from the pharmaceutical industry devoted to this concept are relatively small and there are good reasons why the industry may have been reluctant to invest in developing these types of therapies. In this review article, the hurdles that must be overcome before the pharmaceutical industry might invest in these novel therapies are outlined.     

The return of the pharmaceutical industry to the market of contraception

In the 1980s and 1990s, the litigious climate in the US had a catastrophic effect on sales of many major contraceptives. Although oral contraceptives escaped controversy, the intrauterine device (IUD) and Norplant(R) were two targets of damaging litigation. The IUD was withdrawn from the market in 1985. Since 1994 when the attacks began against Norplant, its US sales have dramatically declined, even though no fault has been found in the method or its development. In general, pharmaceutical companies were extremely hesitant to develop new contraceptives during this period. The bleak outlook, however, began to shift in the late 1990s, as fertility rates began to decrease worldwide and contraceptive users increased. By 2025, 2500 million women will comprise the customer base for contraception. Global pharmaceutical companies are now participating in expanding markets overseas and have launched and continue to develop a range of new long-term reversible, and highly effective, contraceptive products outside the traditional oral contraceptive field. Two new contraceptives on the way to the US market are: Mirena, a levonorgestrel-releasing intrauterine system manufactured by Schering-Leiras; and Implanon, a single implant system manufactured by Organon of the Netherlands. Other birth control methods soon to be launched include: emergency contraceptives, the contraceptive patch, monthly contraceptive injections, mifepristone for medical abortion, and modified oral contraceptives.     

Small molecule pharmacological chaperones: From thermodynamic stabilization to pharmaceutical drugs

A great deal of attention has been paid to so-called amyloid diseases, in which the proteins responsible for the cell death and resultant diseases undergo conformational changes and aggregate in vivo, although whether aggregate formation is the cause or the result of the cell death is controversial. Recently, an increasing attention is given to protein folding diseases tightly associated with mutations. These mutations result in temperature-dependent misfolding and hence inactivation of the proteins, leading to loss of function, at physiological temperature; at low so-called permissive temperatures, the mutant proteins correctly fold and acquire functional structure. Alternatively, activation can be induced by use of osmolytes, which restores the folding of the mutant proteins and hence are called chemical chaperones. The osmolytes are compatible with macromolecular function and do stabilize the native protein structure. However, chemical chaperones require high concentrations for effective folding of mutant proteins and hence are too toxic in in-vivo applications. This limitation can be overcome by pharmacological chaperones, whose functions are similar to the chemical chaperones, but occur at much lower concentrations, i.e., physiologically acceptable concentrations. Although the research and clinical importance of pharmacological chaperones has been emphasized, the initial and central concept of osmolytes is largely ignored. Here we attempt to bridge the concept of osmolytes to applications of pharmacological chaperones.     

Enteroviruses: Classification,diseases they cause,and approaches to development of antiviral drugs

The genus Enterovirus combines a portion of small (+)ssRNA-containing viruses and is divided into 10 species of true enteroviruses and three species of rhinoviruses. These viruses are causative agents of the widest spectrum of severe and deadly epidemic diseases of higher vertebrates, including humans. Their ubiquitous distribution and high pathogenici- ty motivate active search to counteract enterovirus infections. There are no sufficiently effective drugs targeted against enteroviral diseases, thus treatment is reduced to supportive and symptomatic measures. This makes it extremely urgent to develop drugs that directly affect enteroviruses and hinder their development and spread in infected organisms. In this review, we cover the classification of enteroviruses, mention the most common enterovirus infections and their clinical man- ifestations, and consider the current state of development of anti-enteroviral drugs. One of the most promising targets for such antiviral drugs is the viral Internal Ribosome Entry Site (IRES). The classification of these elements of the viral mRNA translation system is also examined.     

Physicians and the pharmaceutical industry: a dysfunctional relationship

The pharmaceutical industry is one of the largest and most profitable industries in the world, and in the United States, the industry has a particularly privileged economic position. Yet the cost of drugs in the United States is higher than anywhere else, due largely to the fact that the industry is focusing increasingly on marketing rather than on the development of meaningful new medications: available evidence does not support claims of great expense for the development of new drugs. Because of its vast resources, the pharmaceutical industry has assumed an increasing influence in medicine, which, given the differences in values and priorities between medicine and the drug companies, is a cause for concern. The pharmaceutical industry has acted to maximize its profits in ways that frequently conflict with medicine's need for truth and full disclosure. Indeed, the industry has arguably worked to compromise physicians' judgments, as well as academic standards. As a result, despite government regulation there have been unnecessary adverse effects from drugs. The experience with butorphanol (Stadol) exemplifies problems in the current system and the harm that can result. Changes are suggested to make the pharmaceutical industry more responsive to the needs of patients and physicians.     

Medical students' exposure to and attitudes about the pharmaceutical industry: a systematic review

Background

The relationship between health professionals and the pharmaceutical industryhas become a source of controversy. Physicians'' attitudes towards theindustry can form early in their careers, but little is known about this keystage of development.

Methods and Findings

We performed a systematic review reported according to PRISMA guidelines todetermine the frequency and nature of medical students'' exposure to thedrug industry, as well as students'' attitudes concerning pharmaceuticalpolicy issues. We searched MEDLINE, EMBASE, Web of Science, and ERIC fromthe earliest available dates through May 2010, as well as bibliographies ofselected studies. We sought original studies that reported quantitative orqualitative data about medical students'' exposure to pharmaceuticalmarketing, their attitudes about marketing practices, relationships withindustry, and related pharmaceutical policy issues. Studies were separated,where possible, into those that addressed preclinical versus clinicaltraining, and were quality rated using a standard methodology. Thirty-twostudies met inclusion criteria. We found that 40%–100%of medical students reported interacting with the pharmaceutical industry. Asubstantial proportion of students (13%–69%) werereported as believing that gifts from industry influence prescribing. Eightstudies reported a correlation between frequency of contact and favorableattitudes toward industry interactions. Students were more approving ofgifts to physicians or medical students than to government officials.Certain attitudes appeared to change during medical school, though a timetrend was not performed; for example, clinical students(53%–71%) were more likely than preclinical students(29%–62%) to report that promotional information helpseducate about new drugs.

Conclusions

Undergraduate medical education provides substantial contact withpharmaceutical marketing, and the extent of such contact is associated withpositive attitudes about marketing and skepticism about negativeimplications of these interactions. These results support future researchinto the association between exposure and attitudes, as well as anymodifiable factors that contribute to attitudinal changes during medicaleducation.Please see later in the article for the Editors'' Summary