News

Food for Thought: Weekly Wrap-Up

Joachim Müller-Jung in Frankfurter Allgemeines Zeitung (FAZ) this week deals with the ethic implications of non-invasive prenatal diagnosis, describing that a huge number of tests based on fetal DNA entering the mother’s blood stream is ready to enter the market. His recommendation is to start an immediate discussion about which tests should be applied and which ones should not.

Ulrich Bahnsen in Die ZEIT interviews Norbert Donner-Banzhoff, Professor at the University of Marburg’s Department of General Practice, Preventive and Rehabilitative Medicine. Donner-Banzhoff conducted a study published in the Canadian Medical Association Journal CMAJ investigating the influence of pharmaceutical advertising on the drug recommendations made in articles in 11 German journals that focus on medical education. Donner-Banzhoff and his team come to the conclusion that journals financed by advertisement from the pharma industry and given away for free almost exclusively recommended the use of specified drugs, whereas journals financed entirely with subscription fees tended to recommend against the use of the same drugs. In the interview, Donner-Banzhoff suggests that a lot of articles published in the free journals have been written by ghost writers and/or members of the pharmaceutical industry.

Matthew Herper in Forbes this week deals with the latest setback in developing drugs to treat Alzheimer’s Disease (AD). He features the failure of Eli Lilly’s semagacest in a Phase III trial in more than 2,600 patients with mild-to-moderate AD. According to an interim analysis, patients receiving the drug, a gamma secretase blocker, worsened to a statistically significant greater degree than those treated with placebo. In addition, the drug was associated with an increased risk of skin cancer. Herper concludes that there is something fundamentally wrong with current hypotheses on the onset of AD and that the failure of the drug may set AD drug development back by many years (see also akampioneer’s recent comment on Probiodrug’s AD hypothesis).

While William Pentland, also in Forbes, reports a potential biofuel breakthrough in producing isobutanol directly from cellulose by using a microbe thriving in decaying grass, Josh Wolfe, co-founder and managing partner of Lux Capital Management, in Forbes states it is time to realize that investing in biofuels may be foolish. He states that while it is hyped as biotech 2.0, there is in fact a fundamental difference to biotech 1.0 which is often overlooked. While biotech 1.0 drugs and molecules can be protected by IP, biofuels cannot. In addition, the marginal cost of producing IP-protected molecules is really low once you did the discovery and first synthesis work (as compared to your margins) – so you can make big profits. Biofuel molecules however have to compete from the onset with the generic fuels already on the market. Biofuel is a commodity, he states, and instead of going back to an agrarian-based economy we should focus on materials and processing based on high energy density, such as uranium.

Donald G. McNeil jr in The New York Times reports on a panel of independent experts from 24 countries that reviewed the handling of the swine flu by the World Health Organization (WHO) in 2009. The draft report – “posted in an obscure corner of the W.H.O.’s Web site” – criticizes the WHO’s “needlessly complex” definition of a pandemic, its inability to deploy 78 million doses donated by rich nations for use in poor ones and its “clumsy communications”.

Colin Barras in New Scientist writes about the origin of cancer and features recent contributions by astrobiologists. While many researchers think that cancer is triggered by a malfunction of the genes trying to control replication which needs to be limited in multicellular organisms, some astrobiologists think a tumor is switching back to some forms of basic cellular cooperation found in the earliest ancestors of multicellular organisms. The distinction is far from being academic: if cancer is some sort of “living fossil” revived it would have only a limited set of survival strategies. In contrast, contemporary medicine regards a tumor as independently evolving cells with nearly unlimited evolutionary potential to escape treatment strategies. The hypothesis explains the co-ordinated survival strategies of cancer, such as angiogenesis and metastasis, and will be further tested soon by genetic profiling.

 

Food for Thought: Probiodrug’s Alzheimer Hypothesis Independently Confirmed

Two decades ago, it was discovered by the founders of German biotech company Probiodrug that the so-called amyloid beta peptides (Aβ) forming the notorious plaques in the brain of Alzheimer’s Disease (AD) patients are not a homogeneous species. While it was known that there are variants in length (from 36 to 43 amino acids), the Probiodrug researchers discovered that there also are pyroglutamated variants (pGlu-Aβ) of the peptides. However, little was known about their origin and biological role. This has changed significantly over the last years, and Probiodrug has pioneered this research.

At this year’s 10th International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2011), taking place in Barcelona/Spain from March 9 to 13, more than two dozen posters and presentations provide further insights into the mechanisms and consequences of pGlu-Aβ formation, and there is overwhelming evidence that pGlu-Aβ is key to understanding Alzheimer’s Disease and to developing novel treatments. Abstracts can be found here.

The findings can be summarized as follows:

1.    Amyloid plaques alone correlate poorly with the severity of AD.

2.    The presence of pGluAβ in plaques, however, does correlate with disease severity in both sporadic and familial AD.

3.    Antibodies recognizing oligomeric forms of pGluAβ bind to plaques in the brains of familial AD patients.

4.    pGluAβ is elevated 8.5-fold in AD brains compared to controls.

5.    pGluAβ forms the center of plaques, with full-length Aβ at the periphery, suggesting that pyroglutamate forms Aβ seed deposits.

6.    pGluAβ is a form of Aβ that aggregates faster than conventional full-length Aβ, is more neurotoxoc and – being protected against degradation – much more stable.

7.    pGluAβ is formed by the enzyme glutaminyl cyclase (QC) at the N-terminus of Aβ by cyclizing a glutamate residue.

8.    Expression of QC is increased in the brain of AD patients.

9.    Mice engineered to express human QC show highly increased levels of pGluAβ as well as motor and memory problems.

10. QC not only produces pGluAβ, but also promotes inflammation by acting on monocyte chemoattractant protein (MCP-1, also known as CCL2), making a pyroglutamate derivative that is stable and resists proteases.

11. Mixtures of pGluAβ and conventional Aβ42 are 10- to 50-fold more deadly to neurons than either peptide alone.

12. Toxicity of these Aβ mixtures depends on the presence of tau, suggesting that tau acts downstream of Aβ.

Novel insights to the hypothesis presented on this year’s AD/PD 2011 include the discovery that QC enzymes are also responsible for the activation of several pro-inflammatory chemokines in the brain by introducing a pGlu-residue. As this residue confers resistance to proteolytic degradation, overexpression or -activity of QC may be involved in turning inflammatory processes into a chronic state of neuroinflammation, which often is observed in CNS diseases.

Another abstract describes a novel ELISA test for the reliable determination of Aβ in biological fluids as well as a novel antibody detecting the biologically active form of an inflammatory biomarker. The ELISA test allows for a clear discrimination between controls showing normal aging and individuals affected by Alzheimer’s Disease in prodromal or demented stages.

 

Company News: bubbles & beyond closes second financing round

bubbles & beyond, a technology company focusing on customized intelligent fluids, has announced the successful closing of a second financing round. All existing investors – LBBW Venture Capital, S-Beteiligungen, Hightech-Gruenderfonds and KfW – participated in the round, which totals EUR 1.2m.

The new funds will be used to strengthen the international market presence of bubbles & beyond and to broaden its internal development capacities in order to meet the increasing demand for customized intelligent fluids™ in various industry sectors. This includes diversified commercialization opportunities in the printing industry, microelectronics, and facility cleaning sectors in Europe and Japan. bubbles & beyond already markets products for graffiti removal as well as cleaning and preservation of building structures on the market. A product portfolio of professional cleaning agents for print rolls will be launched soon. In addition, there is considerable market demand for bubbles & beyond´s intelligent fluids™ in functional cosmetics.

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Food for Thought: Weekly Wrap-Up

In Forbes, Matthew Herper this week deals with the failure of Bydureon eventide, the once-a-week anti-diabetes shot developed by Eli Lilly and Amylin Pharmaceuticals. In a head-to-head Phase III trial Bydureon was not superior to Victoza, the once-a-day drug by Novo Nordisk, in terms of lowering blood glucose levels. Both are synthetic versions of glucagon-like peptide-1, or GLP-1. In another article, Herper looks at the biotech busts and breakthroughs of Februay, from KV Pharmaceuticals (shares up 400%) to Orexigen (shares down 64%). Herper concludes that the rejection of the Orexigen drug Contrave by FDA – the third rejection of an obesity drug in a row – “killed the obesity drug field.”

Wired this week features a story by John Timmer who describes experiments, in which the introduction of engineered viruses boost memory recall in rats. The improment is brought about by a viral protein kinase, but the exact mechanism ist still not understood.

In Germany, Sascha Karberg in Frankfurter Allgemeine Zeitung (FAZ) revisits the attempts to cure AIDS by removing the gene for the receptor protein CCRS, which serves as the entry door for the AIDS virus, from the T cells of HIV-infected patients . Humans lacking the CCRS gene show natural resistance to the disease. The genetically modified T cells are then reinjected into the patients’ blood stream (see akampioneer, January 17). In a Phase I trial of this approach by Sangamo Biosciences, preliminary results have been encouraging, leading to a significant and durable increase of CD4+ T- cell counts in the patients.

Magnus Heier in Frankfurter Allgemeines Sonntagszeitung (FAS) deals with the ignorance of medical doctors in Germany regarding therapy guidelines and attempts to solve the problem by publishing patient versions of the guidelines in the internet.

Richard Stone in Sueddeutsche Zeitung (SZ) features an epidemic in Bangladesh caused by the Nipah virus, which was discovered only in 1998. The virus is spread by bats via raw palm tree juice, a delicacy for both bats and humans. Christina Berndt, also in SZ,  deals with the replacement of members in Germany’s federal “German Standing Vaccination Committee” (STIKO) responsible for handing out advice on vaccination practices. Berndt claims that some of the newly appointed members are too close to industry because they participate in vaccine studies sponsored by vaccine manufacturers.

In a five-part series, Kai Kupferschmidt in German weekly magazine Die ZEIT deals with synthetic biology, this week introducing companies developing synthetic fuels and novel ways to produce drugs. Surprisingly, the article does not feature a single German synthetic biology company but US companies only.

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