Tag: Alzheimer’s disease
Company News: biocrea’s First-in-class PDE2 Inhibitor Demonstrates Strong Potential For The Treatment Of Cognitive Disorders
– Data on novel PDE2 inhibitor BCA909 presented at 24th ECNP Congress in Paris –
biocrea, a biopharmaceutical company focusing on novel treatments for disorders of the central nervous system (CNS), today announced data on its innovative CNS-penetrating PDE2 inhibitor. The compound, which is code-named BCA909, was selected as a candidate for preclinical development earlier this year. It demonstrates strong potential for the treatment of diseases in which normal learning and memory is impaired, e.g. mild cognitive impairment, Alzheimer’s disease and schizophrenia. Details on the compound were presented at the 24th ECNP Congress of the European College of Neuropharmacology in Paris, France (Sept. 3-7, 2011).
To date, few PDE2 inhibitors have been pharmacologically characterized. While initial findings have been encouraging, suggesting pro-cognitive and anxiolytic efficacy, the compounds did not enter the brain in sufficient quantities. With BCA909, biocrea has developed a novel, potent and selective PDE2 inhibitor with excellent CNS penetration and an efficacy and safety profile suitable for further development for multiple disease indications.
During the ECNP congress, biocrea presented data from extensive preclinical studies in vitro and in animal models of learning and memory. The key findings demonstrate that BCA909 delivers significant pro-cognitive activity in models of cognitive impairment resulting from either disruption of cholinergic or glutamatergic neurotransmission. Furthermore, BCA909 does not induce tolerance, indicating that maintained pro-cognitive efficacy, achieved through modulation of multiple neurotransmitter systems, can be delivered by the novel PDE2 mechanism of action.
Preclinical development of BCA909 is ongoing.
Food for Thought: IQWiG Updates Report on Alzheimer Drugs
Galantamine and transdermal rivastigmine plaster can delay loss of cognitive function in Alzheimer’s disease (AD) patients, Germany’s Institute for Quality and Efficacy in Health Care (IQWiG) said in a preliminary report published on its website. In 2007, IQWiG had issued a negative report on the benefit of donezepil, galantamine and rivastigmine, however in 2009 the institute initiated an update, adding additional published and unpublished studies for the appraisal of galantamine and including the rivastigmine plaster which entered the German market in 2007.
IQWiG now states that galantamine at higher doses has a positive effect on cogitation and retentiveness of female patients with mild and moderate AD. However, it added that there was no evidence of improvement of daily routine abilities or psychopathological symptoms such as unrest and depression in both male and female patients. In addition, IQWiG notes that patients often dropped out of the study because of side effects such as nausea, vomitus or diarrhea. It also states that it did not find evidence supporting a galantamine treatment for more than 12 months.
For the rivastigmine plaster, IQWiG said it found hints that the 10 square centimeter plaster improves cognition of patients under 75 years of age; however it states that the data were not resilient enough to support an assessment as “proof of efficacy.”
IQWiG said that both manufacturers, the pharma companies Janssen-Cilag and Novartis, provided all study data requested by IQWiG, including unpublished data comprising 48% of study patients. Juergen Windeler, head of IQWiG said in a statement that this was further underlining the necessity to introduce mandatory publication of clinical study data.
Food for Thought: Weekly Wrap-Up
Andreas Sentker in Die ZEIT takes up the issue of rising eco-terrorism in Germany directed against field trials of genetically modified plants. These plants are an easy target as trial sites have to be disclosed to the public in registers following legislation initiated by the former red-green coalition in Germany. While in the past years opponents of genetically modified plants only targeted the plants they dub as “Gen-Dreck”, violence is now also directed against security firms and guards watching the fields. Last week, a masked gang assaulted security guards, looted their mobile phones and destroyed different plants of research projects from the University of Rostock. The plants were carrying genes for the production of biopolymers and for a vaccine against viral diseases.
In Süddeutsche Zeitung (SZ), Hanno Charisius introduces efforts to create artificial leaves mimicking photosynthesis to create hydrogen which can be used as fuel or energy source. Daniel Nocera from the Massachusetts Institute of Technology (MIT) is just using the principle: water molecules are split using electrical current produced by solar cells – an ages-old principle. Noceras new twist, however, is the use of a mix of cobalt and phosphate as a catalyst. The mix is accumulating at the electrodes, but after a while it is crumbling and thereby regenerating. The reaction is not the most effective one, but prototypes are already running for months without efficiency drop. First machines will now be installed in India for tests in realistic conditions; the goal is to meet the daily power demand of an Indian family by using just 4 liters of water and sunlight. Nocera is now trying to combine his catalyst with solar cells to a single device.
Katrin Blawat, also in SZ, in a somewhat pessimistic article deals with the many failures to develop a drug to combat Alzheimer’s disease. Given that there are neither cures nor effective therapies to prevent or delay the onset of AD, she cautions against tests for early diagnosis.
Another negative outlook is given by Werner Bartens in the same paper. Bartens deals with personalized medicine, calling the concept a “set phrase” invented to disguise that personalized medicine is a mere “PR strategy by the pharma industry and stakeholders from academia” invented to lay a smoke screen on the failure to develop new blockbuster drugs. For Bartens, the “niche buster concept” is “science fiction” allowing the pharma industry to obtain approval without any proof of patient benefit. As an example, Bartens interestingly mentions the introduction of personalized cancer drugs of which only a fraction of the patients is benefitting.
In contrast, Ronald D. Gerste in Neue Zürcher Zeitung (NZZ) writes about how cancer patients have profited from targeted therapies, e.g. in terms of decreasing cancer mortality and improved survival. Gerste features a trial by the MD Anderson Center in Houston/Texas in which 460 cancer patients underwent detailed molecular genetic analysis. Subsequently, they were treated by a matching therapy addressing the most promising molecular mechanism. Without applying any experimental drugs, this procedure increased survival from 9 to 13.4 months on average.
Also in NZZ, Stefan Betschon makes the case for better science communication, introducing an article by Dirk Helbing and Stefano Bialetti on “how to create an innovation accelerator“. They propose to improve the academic publication system by publishing articles ahead of peer review finalization and call for review by crowd sourcing. Rejected publications should also be made public, alongside with comments.
The Economist this week casts doubt on whether the goal to eradicate polio by the end of 2012 can be met. The disease is still endemic in four countries (Afghanistan, Pakistan, India and Nigeria), however re-emerged in African and Asian countries in recent years. Reasons are political (war, refugees, etc.), socioeconomic (poor sanitation) and medical (vaccines needs cold chain, virus can hide in asymptomatic carriers) factors.
Another article in The Economist deals with epigenetics findings by a German research group from the University of Konstanz. The team found that stress during pregnancy (abuse, violence, famine, death of a relative etc.) can lead to a change in the DNA methylation patterns of the unborn child, e.g. of the gene coding for glucocorticoid receptors which relay signals from stress hormones in the blood to cells of the brain regions controlling behavior. The findings may explain why children of stressed mothers show higher-than-normal rates of psychological and behavioral disorders and may lead to insights about how and when interventions are possible and promising.
Andrew Pollack in the New York Times features discussions on changing the rules for research in human subjects. The US government claims that changes are needed in the light of genomics studies using patients’ DNA samples, the use of the Internet and a growing reliance on studies that take place at many sites at once. Among the proposed changes are adding informed consent rules to donors of blood, DNA or tissue samples and allowing a single institutional review board for multiple-site clinical studies.
And finally, for all of us struggling daily with the touchscreen keyboards of our iPads and iPhones, IBM comes with a solution: a keyboard that morphs to fit an individual’s finger anatomy and typing style. Paul Marks in Wired dug out an IBM patent describing keyboards in which buttons are automatically resized, reshaped and repositioned according to the users typing style.
Food for Thought: Weekly Wrap-Up
First signs of future onset of Alzheimer’s disease (AD) can be found already at the age of 14, reports Volker Stollorz in Frankfurter Allgemeine Sonntagszeitung (FAS). Introducing findings by Heiko Braak and Kelly del Tredici from Ulm University, he also points out that AD seems to originate in the Nucleus coeruleus region of the brain stem from which the typical AD clots slowly spread alongside nerve tracts. Stollorz features plans to include members of families with hereditary forms of AD in future clinical trials to test preventive drugs and treatments. Researchers in Germany currently are planning to launch a website and to found a network modeled according to the US “Dominant Inherited Alzheimer Network” (DIAN). Stollorz and his colleague Thomas Liesen also are co-authors of a TV documentary which can be found here for four weeks from July 19, 2011.
Jutta Hoffritz in Die Zeit reports on novel anticoagulants, e.g. Pradaxa by Boehringer Ingelheim, which is already marketed in the US, and similar drugs developed by Bayer Schering, Pfizer and Daiichi Sankyo. The drugs are developed to replace marcumar which carries the risk of severe side effects and is difficult to dose. However, while the new drugs show better efficacy and promise better compliance, Hoffritz cites German medical doctors expressing skepticism because of unknown long term risks and the anticipated high pricing of the drug. Ulrich Schwabe, editor of Arzneiverordnungsreport, a publication known to be very critical about the pharma industry, is quoted with the calculation that treating all eligible patients in Germany with Pradaxa would amount EUR 4.9 billion per year. The calculation is based on the price of the current daily dosis as the drug is already marketed in Germany for the prevention of thrombosis prior to knee and hip replacement surgery.
Christian Heinrich also in Die Zeit features a trend among pharma companies to search for potential applications of their already approved drugs. As an example, he introduces the “Common Mechanism Research” department of Bayer Schering AG, which is systematically studying unusual effects of Bayer compounds to find clues for novel therapeutic applications. Well-known examples of dual use compounds are sildenafil, which was originally developed to treat circulatory disturbance of the heart (now a common drug to treat erectile dysfunction), and aspirin, which was known as a pain killer and only later developed as anti-coagulant.
Christina Hucklenbroich in Frankfurter Allgemeine Zeitung (FAZ) reports on the suspicion that recently observed deaths of cattle in Germany may be caused by Clostridium botulinum bacteria. However, she points out the the jury is still out on whether there is a novel zoonosis called chronic botulism as presence of the toxin in minute amounts in the gut of affected animals is difficult to confirm. In addition, the source of the bacteria detected in some animals has not yet been identified.
Also in FAZ, Hildegard Kaulen reports on novel findings how smoking cigarettes suppresses appetite. Researchers from Yale University, she writes, found a hitherto neglected nicotine receptor in the brain, which influences the neuronal circuit involved in appetite regulation. Once nicotine binds to the receptor, the nerve cells start releasing the neurotransmitter POMC which in turn influences nerve cells regulating satiety feelings.
Nicholas Wade in The New York Times reports on efforts by scientists from Harvard Medical School to introduce hundreds of changes in the genome of E. coli bacteria simultaneously, an effort dubbed by a colleague as as “macho molecular biotechnology”. The alteration of 314 sites is just an intermediate step by George M. Church and Farren J. Isaacs to establish a method by which certain stretches of DNA could be changed just the way a word processor searches and replaces certain words in an entire document in one step. The researchers removed a particular stop codon (T-A-G, or “amber”) and replaced it by another (which works just as well). Now they are planning to also remove the gene recognizing the deleted stop codon and subsequently to reintroduce amber and reassign it a new function, e.g. to incorporate a novel amino acid into the bacterium’s proteins.
The Economist announces the world’s first “World Cell Race” taking place in August. Cells sent in by various research institutions all over the world will compete against each other in the race to move towards a chemoattractant. The scientists thereby hope to identify genes involved in cell mobility which are known to be important drivers in cancer metastasis as well as wound healing and immune responses.
New Scientist recently featured a series of articles dealing with bacteria (“bugs that break all rules”): Caroline Williams introduces multicellular behavior of socializing bacteria, features bugs that hunt in packs, bacteria large enough to be visible with the naked eye and bacteria with backbones and cell compartments.
And finally, Cinthia Briseno in Der Spiegel reports on studies proving that the internet is changing the way we memorize and learn. The ability to rely on the internet seems to encourage people to make less mental notes of facts they are sure to find in the web with a few keystrokes.