2013: New cancer therapies, intestinal bacteria as helpers and viruses as a threat

Cologne - At the end of the year, the science magazine Science declared cancer immunotherapy to be the scientific breakthrough of 2013. The approach to fighting cancer with the weapons of the immune system is by no means new. In the broadest sense, it also includes the monoclonal antibodies that have been introduced in recent years. Rituximab (1998) was followed by trastuzumab, alemtuzumab (2001), ibritumomab-tiuxetan (2004), cetuximab (2004), bevacizumab (2005), panitumumab (2006) and ofatumumab (2010). They all attack the tumor (or its blood supply) directly and thus partly take over the task of the immune system.

The antibody ipilimumab, introduced in 2011, tries to strengthen the body's immune defense by releasing "built-in brake" . This brake, the protein CTLA-4 (Cytotoxic T-Lymphocyte Antigen-4), normally keeps T cells in check. It is likely natural protective mechanism against autoimmune diseases. Ipilimumab triggers an uninhibited immune defense.

In malignant melanoma, the most malignant tumor with the shortest survival time in the metastatic stage , thanks to ipilimumab, long-term survival is possible for the first time. Some patients have survived their melanoma for more than ten years thanks to ipilimumab (the drug does not work for others, which is why the median survival rates are less impressive).

The effect of ipilimumab can be increased by giving an additional antibody . Nivolumab releases another blockade of the immune system by binding to PD-1 (programmed death 1). The first results of Phase I study in melanoma, which were published in July, are promising. A special feature of the new antibodies is that they do not take effect immediately. Often weeks or even months pass before the tumor shrinks. Sometimes this is only the case after the end of therapy. This can be explained by the mechanism of action.

The success of the active ingredients depends on the immune system seizing the opportunity that opens up. Sooner or later this may or may not happen at all. The success of cancer immunotherapy with the new antibodies seems to depend more or less on chance.

Another form of immunotherapy does not want to rely on this. In CAR therapy, T cells are equipped in the laboratory with the weapons that make them persistent hunters of tumor cells when they return to the body. The weapons consist of the gene for chimeric antigen receptor (CAR), which recognizes specific features on cancer cells.

CD19 is available for B-cell tumors, which also include chronic lymphocytic leukemia (CLL) on, surface protein typical of B cells.After the re-infusion, the T cells multiply, which has led to surprisingly long-lasting remissions in the first clinical trials in patients with CLL who no longer responded to chemotherapy. Clinical studies with CAR are currently also being carried out on solid tumors.

Intestinal bacteria as helpers and pathogens There are about ten times more bacteria in the intestine than the entire human body has in cells. Thanks to advances in gene sequencing, it is now possible to take rough inventory of the intestinal flora. In recent years this has led to new insights into the symbiosis of humans and intestinal flora. The type of intestinal bacteria sometimes decides in curious way about health and illness. So fell ill in China in 2008 because the manufacturers added melamine to the dry milk for baby food. Not all children got sick. Kidney stones only developed when the intestine was colonized with Klebsiella. These bacteria break down melamine into cyanic acid, which then forms concrements in the kidneys.

Intestinal bacteria can starve person. In some children with the hunger disease kwashiorkor there is an incorrect colonization of the intestines with bacteria. They prevent the therapeutic food RUTF (“Ready-to-Use Therapeutic Food”) from being absorbed by the intestine. Around 5 to 10 percent of malnourished children die in this way at the hands of development workers. .

Intestinal bacteria can also make you fat. The composition of the intestinal flora may explain why some people are good eaters, but others stay slim despite high calorie intake. One of the potential slimming agents stayed slim in experiments, even if they were fed high calorific values. They did not develop diabetes.

The shortening of the intestines, in which many obese people see their last chance at weight loss, could at least partly owe its effect to the intestinal bacteria:. Akkermansia was again one of the bacteria that multiplied after the operation. A transplant of the intestinal bacteria could even be an alternative to surgery, the researchers suspected (however, clinical evidence is still lacking).

Wrong bacteria in the intestine make you sick. One. According to the findings, the bacteria metabolize carnitine (from red meat) and lecithin (from eggs) into trimethylamine (TMA), the increase in blood levels of which was associated with an increased risk of cardiovascular events in two studies.

intestinal bacteria could also explain why patients with ulcerative colitis are more likely to develop colorectal cancer.Inflammatory bowel disease is associated with an increased colonization of the intestine with fusobacteria and two research groups reported in October that they had found precisely this group of bacteria (or rather their genes) in colon cancer tumors.

. In an experimental immunotherapy with CpG oligonucleotides, they were needed to stimulate the immune system to produce tumor necrosis factor. The cytostatic drug oxaliplatin also seems to be dependent on cooperation from the intestine. Concomitant antibiotic therapy has led to the failure of cancer therapy in animal studies. Cyclophosphamide works better when it comes to mucositis, because the disruption of the intestinal barrier causes bacteria to enter the bloodstream, which could mysteriously increase the therapeutic effect.

Further studies last year included rheumatoid arthritis the intestinal germ Prevotella copri, while Lactobacillus johnsonii protected dogs from allergies in the intestine. In another study, treatment with other bacteria saved mice from "autistic" behavioral disorders.

Many of these experiments were carried out on animals. It is unclear what therapeutic consequences result for humans from this. However, those made with faecal transplantation for intestinal rehabilitation in Clostridium difficile-associated diarrhea (CDAD) give reason to hope that one or the other application will result.

Threat from new and well-known viruses Two new “emerging” viruses entered the stage in 2013 without, however, triggering the initially feared epidemic. At the beginning of April, the World Health Organization (WHO) reported that the influenza virus H7N9, which is spread among birds, had infected humans for the first time. As result, however, there were isolated diseases. By December only 143 patients fell ill, but 45 of them died. The virus is therefore highly pathogenic, but not very contagious. Transmission among humans is rare, so the prerequisites for serious epidemic have not yet been met.

The Middle East respiratory syndrome, or MERS coronavirus, has not spread either. The WHO counted 170 diseases by the end of December, 70 of which were fatal. MERS appears to be transmitted from person to person more often than H7N9. Even one who infected several people at the same time could be identified. Overall, however, the risk of prolonged epidemic is viewed as low. As with H7N9, most patients became infected with animals. The most likely reservoir are or certain species that are only native to the Arabian Peninsula, where all previous diseases had their origin.

The polio virus is one of the older viruses.Rotarians have set themselves the goal of eradicating the polio pathogen modeled on the smallpox virus worldwide. It is thanks to the Global Polio Eradication Initiative that the number of cases has fallen dramatically over the past few decades. Eradication has been in sight since 2001, but since then the initiative has repeatedly suffered new setbacks.

In the case of HIV, eradication currently appears to be ruled out as there is still no effective vaccine. The global number of infected people is likely to have increased again by several million in 2013 (2012: plus 2.3 million). The risk of infection can, however, be significantly reduced through consistent therapy of the infected. This was one of the reasons the World Health Organization. A start should now be made when the CD4 cells drop below 500.

The drugs cannot completely eliminate the viruses from the body. An exception may be patients who are treated in the early stages of the infection, before the viruses have established themselves in their reservoirs in the immune system. So far, elimination has only been successful in some who were already treated in the acute phase, as well as in newborn in the US state of Mississippi. There, antiretroviral therapy achieved “” in the first few weeks of life.

The viruses are among the viruses that are underrated worldwide. According to study in April, the number of people infected is 390 million people three times as high as previously assumed, and British researchers fear that some visitors to the football World Cup in Brazil could also get to know the virus next year.

Sleep - vital medicine Research is far from being able to explain the elementary functions of the human body. It is still mystery why humans - and most other vertebrates as well - spend about third of their lifetimes in sleep. In general, regeneration (of the body's strength), calibration (of the body's functions) and also the processing of memories (memory formation) are named as reasons.

Last year, US researchers were able to prove.During the nocturnal rest phase, the interstitial spaces in the brain expand to form “glymphatic” system through which toxic metabolic products are removed from the brain. The waste also includes beta-amyloids, the accumulation of which in the brain is known to be the trigger for Alzheimer's disease. The study results could explain why seniors with sleep disorders have increased deposits of beta-amyloids in the brain.

A restful sleep is important for maintaining health . Other studies over the past year have shown that sleep disorders disrupt the internal clock, damage the heart muscle and increase risk. Those who allow themselves too little sleep increase their appetite and the development of one that further reduces the quality of sleep. This cycle can be achieved through sleep hygiene and perhaps also relaxation exercises other than taking sleeping pills.

Intelligent prostheses and other mechanical aids Robots and prostheses cannot completely replace skills that have been lost, but they can do an important one Be help. In December 2012, US doctors showed what is possible in principle today with brain-computer interface. A tetraplegic woman was able to use her thoughts, which were read via two epidural brain implants, to move the hand of robot and perform simple actions.

, which enables intended movements in the knee and ankle. A patient with thigh amputee was able to climb stairs with the prosthesis without any problems, negotiate inclined planes and (though sitting on chair) kick away leaked soccer ball. , which enabled quadriplegic patient to control wheelchair by moving their tongue. The "interface" between body and machine was taken over by magnetic tongue piercing.

To be located in the gray area between science fiction and reality, the project, as it is also used in inkjet printers, is to be merged into retina . This could restore vision to patients with retinitis pigmentosa or other degenerative diseases of the retina. A British research group was able to show that the cells survive the printing process. A first, small step towards therapeutic application.

The production of complex organs is currently still overwhelming for bioengineers. Stem cells are superior to them here. What the researchers have to laboriously work out is written in the stem cells' genome. Targeted impulses at the right time in bioreactor are sufficient and the primordial cells of the human body begin to form small organs on their own.

Researchers from Austria allowed themselves in this way by the brownies of the. Only in the absence of suitable blood supply did development stall in the early embryonic stage. Brains are not one of the therapeutic goals of research anyway. With liver or kidney, however, many patients on the waiting list of the transplant centers would already be helped. It is currently still uncertain whether and when the stem cells can be instigated.

New vaccines "Made in China" The development of new vaccines is no longer the domain of western scientists. China and India have made efforts in recent years to protect their populations from diseases that are common in Asian countries. In October recommended the. The vaccine protects against Japanese encephalitis, which is also common outside of Japan in East Asia. Another vaccine against hepatitis E could follow shortly.

Chinese researchers also successfully tested vaccine against human enterovirus 71 last year,. More than million people develop it in China every year and several hundred die from it. In May one announced that it would cost only 54 rupees (the equivalent of 1 euro) instead of 1,000 and would therefore also be affordable for the countries in Africa and South Asia, where the diarrheal pathogen causes most deaths.

One Vaccine against malaria, the most important tropical disease, does not yet exist. Has only limited effect. It could still be approved in 2014.

At the end of the year, mice had good humoral and achieved local immunity. Should the vaccine prove to be safe and effective in humans, it would also be of interest to Western countries. Half of humanity is said to be infected with H. pylori. The bacterium not only causes gastritis and peptic ulcers, it is also responsible for gastric cancer and MALT lymphoma and is therefore classified as group 1 carcinogen.

The experience of meningitis shows how successful vaccines could be in developing countries Vaccine Project, which is specially designed for Africa. The number of illnesses fell by 94 percent.

Vaccinations sometimes have unexpected consequences. The selection pressure can lead to the development of new pathogen variants against which the vaccine loses its effectiveness. This development is currently threatening with Bordetella pertussis, the causative agent of whooping cough. Pathogens are spreading in the US, central component of the cellular vaccines introduced in the 1990s.Vaccination experts wonder whether the mutations are responsible for the recent major whooping cough epidemics, which occurred in California in 2010 and Washington in 2012. In China, the routine vaccination of children against hepatitis B has led to the spread of mutants of the virus in which the current vaccine no longer works.

DSM-V: Content and fundamental criticism of the US Psychiatry Bible In May, the United States launched the. There was lot of criticism in advance. It not only concerned the recording and definition of individual mental illnesses such as borderline syndrome and ADHD, which always also follow social norms in which the USA often differs from Europe. Some critics also missed burnout syndrome or internet addiction, others argued that Asperger's syndrome was added to the autism spectrum disorder.

The most violent criticism, however, came from the director of the National Institute of Mental Health, who denied any validity to the DSM-V in his blog. The DSM-V is by no means the bible of psychiatry as it is often referred to, wrote Thomas Insel. At best it is “dictionary” that defines certain diseases without specifying biological basis for them.

Insel expects that research results in the next few years will turn psychiatry from the head back onto biological basis. Some studies published last year showed what is meant by this. A genome-wide association study came to the conclusion that major depression, bipolar disorder, schizophrenia, autism spectrum disorder and attention deficit / hyperactivity disorder. Another study suggests one.

The same gene variants seem to favor susceptibility to different psychiatric illnesses. According to the new way of thinking, which symptoms occur could become increasingly irrelevant. Another study showed that one in ten, if they were responsible for the psychosis, would in future have to classify schizophrenia with lupus erythematosus and rheumatism in the group of autoimmune diseases.

US recommendations: More statins - less blood pressure medication If US guidelines send signal to German doctors, the number of statin prescriptions is likely to increase in the next few years. The American College of Cardiology and the American Heart Association waived their in November. The US cardiologist associations would like to treat all adults whose 10-year risk of cardiovascular event is above 7.5 percent with statins - and this specifically also if the cholesterol level is not elevated at all. The underlying rationale, which the US associations spread out over 84 pages, does not make sense to German professional associations.They unanimously criticized the new US recommendations, which would mean that 44 percent of all men and 22 percent of all women would have to be treated with statins.