12 October 2016

Twenty Medical Breakthroughs That May Be Just Around The Corner

What are some potential and promising near future medical breakthroughs?

Here are twenty of them (sometime more than one in a single bullet point):

Scientists have designed a new generation of universal flu vaccines to protect against future global pandemics that could kill millions. Researchers researchers have devised two universal vaccines; a USA-specific vaccine with coverage of 95% of known US influenza strains; and a universal vaccine with coverage of 88% of known flu strains globally.
* Other broad spectrum vaccines may leverage an increased understanding of B cells in lymph nodes which are part of the body's natural immune system.

* Ordinary seasonal flu shots for pregnant women can reduce the risk of a stillbirth by 51%.

* A "vaccine" that would cause opioid addicts to cease to respond to opioids or even to particular sub-classes of opioids. This could revolutionize substance abuse treatment for the leading cause of overdose deaths in the United States.  One of these "vaccines" is mixed with a true vaccine component that reduces HIV infection risk by one-third. See also here. There are also non-vaccine oriented drug treatments for opioid addiction (some of which are getting better) and drug treatments for alcoholism.
Scientists are searching for a different kind of shot to prevent such tragedies: a vaccine to counter addiction to heroin and other opioids, such as the prescription painkiller fentanyl and similar knockoff drugs. In some ways, the vaccines work like traditional vaccines for infectious diseases such as measles, priming the immune system to attack foreign molecules. But instead of targeting viruses, the vaccines zero in on addictive chemicals, training the immune system to usher the drugs out of the body before they can reach the brain. . . . 
The term opioid refers to a host of painkillers derived from the opium poppy as well as synthetic versions of its active compounds. Heroin is processed from morphine, which is extracted from the plant. Prescription medications such as Vicodin, Percocet, OxyContin and fentanyl are made from synthetic morphine, altered to produce different effects. 
Currently, three medications, sold under various brand names, are available to help people with heroin or opioid addiction get clean and stay drug-free: methadone, buprenorphine and naltrexone. The treatments work, Volkow says, but not perfectly. Some addicted patients, such as Schnur, experience unwanted side effects from the daily or monthly treatments and stop using them. Others lack access to treatments due to high costs and strict federal limits on dispensing the drugs. 
“Unfortunately, only a small percentage — about 25 percent — of people who could benefit from treatment actually get these medications,” Volkow says. . . . 
In the late 1990s, scientists resumed antidrug vaccine efforts, focusing on vaccines for everything from cocaine to nicotine to heroin (SN: 2/10/07, p. 90). Vaccines for nicotine and cocaine were tested in people, but worked for only a small percentage. 
Now, to help combat the growing opioid addiction crisis, two vaccines for heroin users are advancing toward human trials and other antiopioid vaccines are in the pipeline, including one for fentanyl, now a popular street drug. . . . 
In rats, the three-pronged vaccine generated high numbers of antibodies against the drug and its metabolites, blocking heroin’s action on the brain. Once vaccinated, the formerly addicted rats were unable to get high, even when injected with extremely high doses of the drug, Janda’s group reported in 2013 in the Proceedings of the National Academy of Sciences. The result was decreased drug-seeking behavior in the vaccinated rats. By contrast, control rats, and those vaccinated only against morphine, continued to seek higher doses of the drug. 
The vaccine showed similar effectiveness in nonhuman primates, Janda reported in May at the American Psychiatric Association’s annual meeting in Atlanta. In addition, the vaccine is specific to heroin metabolites, not other opiates. A vaccine that’s too broad could potentially make patients immune to the effects of all prescription opioids, leaving them vulnerable if they become injured and need pain relief. 
Janda’s team recently tested another antiopioid vaccine in animals, one that arms the body against fentanyl. When given to mice, the vaccine trained the animals’ immune systems to generate antibodies that bind to fentanyl and prevent it from traveling to the brain from the bloodstream. The results, published March 7 in Angewandte Chemie, showed that in mice, the antibodies neutralized high levels of the drug — more than 30 times a normal dose — for months after a series of three shots. By blocking the effects of the drug and its high, the vaccine could potentially curb drug-seeking behavior. 
Another group is going after heroin and its strong tie to high HIV infection rates worldwide. Scientists at the Walter Reed Army Institute of Research are developing a dual-purpose vaccine, called H2, to treat heroin addiction while preventing HIV infection. 
Biochemist Gary Matyas and his group at Walter Reed first designed a vaccine to stimulate antibodies against heroin. Similar to Janda’s antiheroin vaccine, haptens are bound to a protein carrier, spurring the immune system to create high levels of antibody to bind heroin and its metabolites in the blood and prevent it from crossing the blood-brain barrier. Users will then experience no euphoria or addictive reactions. 
The researchers plan to combine the heroin vaccine with an HIV vaccine, a combination that’s much trickier to develop. Scientists have long been frustrated by the ability of the AIDS virus to mutate and evade the immune system. The virus constantly changes the makeup of the proteins on its surface so that antibodies have difficulty recognizing and attacking it. But researchers have found that targeting a region called V2 on the surface of the virus decreased the risk of HIV infection. 
The vaccine, tested in volunteers in Thailand by the country’s Ministry of Public Health and Walter Reed scientists, protected about a third of participants against HIV infection, according to a 2009 report. 
* An experimental drug would reduce the harm caused by traumatic brain injuries by controlling the amount of inflammation in the brain that they cause. It will enter clinical trials in a few years.

* A drug to prevent migraine headaches has been developed.
Neurologists believe they have identified a hypersensitive nerve system that triggers the pain and are in the final stages of testing medicines that soothe its overly active cells. These are the first ever drugs specifically designed to prevent the crippling headaches before they start, and they could be approved by the U.S. Food and Drug Administration next year [Ed. i.e. in 2016]. If they deliver on the promise they have shown in studies conducted so far, which have involved around 1,300 patients, millions of headaches may never happen. . . .
In two placebo-controlled trials with a total of 380 people who had severe migraines up to 14 days per month, a single dose of a CGRP drug decreased headache days by more than 60 percent (63 percent in one study and 66 percent in the other). In addition, in the first study, 16 percent of the patients remained totally migraine-free 12 weeks into the 24-week trial. Larger clinical trials to confirm those findings are currently under way. So far the CGRP drugs work better at prevention than any of the borrowed heart or epilepsy drugs and have far fewer side effects. They are given to patients in a single monthly injection.
 * Three new drugs effective against drug resistant pathogens are derived from traditional remedies that actually work. A traditional medicinal clay is effective against multiple drug resistant pathogens. So does a thousand year old Anglo-Saxon "potion" which is 90% effective against MSRA for unknown reasons: "The recipe calls for two species of Allium (garlic and onion or leek), wine and oxgall (bile from a cow’s stomach). It describes a very specific method of making the topical solution including the use of a brass vessel to brew it in, a straining to purify it and an instruction to leave the mixture for nine days before use." So do compounds found in pro-biotic meads that were popular with the Vikings a thousand years ago.
[A] collection of microorganisms—so-called “lactic acid bacteria,” or LABs— . . . live inside the honeybee’s crop, a special stomach devoted to nectar collection. These bacteria are a living factory of medicine, exuding a suite of suite of antimicrobial compounds that target and kill pathogens. In 2014, Olofsson published a study showing that honey inoculated with thirteen LABs could treat chronic, antibiotic-resistant wounds in horses. In the lab, the same microbial cocktail eliminates deadly human pathogens, including the notoriously drug-resistant MSRA.
* Treatment of toxoplasma gondii parasitic infections (which are usually considered harmless and found in 30% of adults worldwide and 9% of American control group test subjects) could cure as many as one in five individuals with intermittent explosive disorder who have such infections at an elevated rate.
Individuals with a psychiatric disorder involving recurrent bouts of extreme, impulsive anger--road rage, for example--are more than twice as likely to have been exposed to a common parasite than healthy individuals with no psychiatric diagnosis.

In a study involving 358 adult subjects, a team led by researchers from the University of Chicago found that toxoplasmosis, a relatively harmless parasitic infection carried by an estimated 30 percent of all humans, is associated with intermittent explosive disorder and increased aggression. 
The findings are published in the Journal of Clinical Psychiatry on March 23, 2016. 
"Our work suggests that latent infection with the toxoplasma gondii parasite may change brain chemistry in a fashion that increases the risk of aggressive behavior," said senior study author Emil Coccaro, MD, Ellen. C. Manning Professor and Chair of Psychiatry and Behavioral Neuroscience at the University of Chicago.
* An anti-cancer drug may postpone the onset of Alzheimer's disease.
The drug, which is an approved anti-cancer treatment, has been shown to delay the onset of Alzheimer's disease, both in a test tube and in nematode worms. It has previously been suggested that statin-like drugs -- which are safe and can be taken widely by those at risk of developing disease -- might be a prospect, but this is the first time that a potential 'neurostatin' has been reported. 
When the drug was given to nematode worms genetically programmed to develop Alzheimer's disease, it had no effect once symptoms had already appeared. But when the drug was given to the worms before any symptoms became apparent, no evidence of the condition appeared, raising the possibility that this drug, or other molecules like it, could be used to reduce the risk of developing Alzheimer's disease. The results are reported in the journal Science Advances. 
By analysing the way the drug, called bexarotene, works at the molecular level, the international team of researchers, from the University of Cambridge, Lund University and the University of Groningen, found that it stops the first step in the molecular cascade that leads to the death of brain cells.
* A gene in adult humans is protective against hardening of the arteries which is a major cause of cardiovascular death in older people. Drugs that target that biochemical pathway utilized by the gene could dramatically reduce this form of heart disease.
The gene, Oct4, plays a key role in the development of all living organisms, but scientists have, until now, thought it was permanently inactivated after embryonic development. Some controversial studies have suggested it might have another function later in life, but the UVA researchers are the first to provide conclusive evidence of that: Owens and his colleagues have determined the gene plays a critical protective role during the formation of atherosclerotic plaques inside blood vessels. The rupturing of these plaques is the underlying cause of many heart attacks and strokes. 
The researchers found that Oct4 controls the movement of smooth muscle cells into protective fibrous "caps" inside the plaques -- caps that make the plaques less likely to rupture. The researchers also have provided evidence that the gene promotes many changes in gene expression that are beneficial in stabilizing the plaques. This is exciting, because studies suggest that it may be possible to develop drugs or other therapeutic agents that target the Oct4 pathway as a means to reduce the incidence of heart attacks or stroke. "Our findings have major implications regarding possible novel therapeutic approaches for promoting stabilization of atherosclerotic plaques," said Olga A. Cherepanova, PhD, a senior research scientist in Owens' lab.
* Removing a defective grain of rice sized organ called the carotid body in people can cure people with high blood pressure, a potentially deadly condition. The first stage of clinical trials for this treatment were completed in 2013 or 2014.

* A new class of drugs that targets a certain kind of enzyme in the body called "salt-inducible kinases" may be able to treat a broad spectrum of autoimmune diseases like Crohn's disease, arthritis, and psoriasis.
"Our laboratory studies further expand and validate the potential therapeutic implications of the use of salt-inducible kinase inhibitors for the treatment of immune-mediated inflammatory diseases," said Maria Stella Lombardi, Ph.D., a researcher involved in the work from the University of Geneva in Switzerland. "The development of novel potent, selective, and drug-like inhibitors of the these pathways will allow us in the near future to test them in animal models of chronic inflammatory and autoimmune diseases."
* A new drug derived from a traditional medicinal plant may halt the progression of M.S. and might even have applications to other autoimmune diseases.
An international research team has demonstrated that a new plant-derived drug can block the progression of multiple sclerosis (MS). University of Queensland researcher Dr Christian Gruber said the breakthrough could be a step forward in preventing and treating MS and other autoimmune diseases. 
"This is a really exciting discovery because it may offer a whole new quality of life for people with this debilitating disease," he said. 
The new drug is expected to be taken by mouth, in contrast to some current MS treatments where patients need to have frequent injections. . . . Dr Gruber said the new drug -- named T20K -- was extracted from a traditional medicinal plant, the Oldenlandia affinis.  
The drug treatment had been successful in an animal model, and patent applications filed in several countries. "Phase one clinical trials could begin as early as 2018," Dr Gruber said.
* Treatment with a pregnancy hormone can also reduce the likelihood of a recurrence of M.S.
In addition to a standard MS drug, 164 women with MS received either a placebo or estriol, an estrogen made by the placenta that peaks toward the end of pregnancy. After two years, women who received estriol had an average of 0.25 relapses a year, while women who received the placebo had 0.37 relapses a year, UCLA neurologist Rhonda Voskuhl and colleagues write online November 24 in Lancet Neurology.
* A new form of radiation treatment for prostate cancer fails seven to fourteen times less often than existing treatments. 
A five-year study shows that Stereotactic Body Radiation Therapy (SBRT) to treat prostate cancer offers a higher cure rate than more traditional approaches, according to researchers at UT Southwestern Medical Center Harold C. Simmons Comprehensive Cancer Center.

The study -- the first trial to publish five-year results from SBRT treatment for prostate cancer -- found a 98.6 percent cure rate with SBRT, a noninvasive form of radiation treatment that involves high-dose radiation beams entering the body through various angles and intersecting at the desired target. It is a state-of-the-art technology that allows for a concentrated dose to reach the tumor while limiting the radiation dose to surrounding healthy tissue. 
"The high cure rate is striking when compared to the reported five-year cure rates from other approaches like surgery or conventional radiation, which range between 80 to 90 percent, while the side effects of this treatment are comparable to other types of treatment," said Dr. Raquibul Hannan, Assistant Professor of Radiation Oncology and lead author for the study. "What we now have is a more potent and effective form of completely noninvasive treatment for prostate cancer, conveniently completed in five treatments."

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