Phoenix Down

Human immune cells in blood can be converted directly into functional neurons in the laboratory in about three weeks with the addition of just four proteins, researchers at the Stanford University School of Medicine have found.

The dramatic transformation does not require the cells to first enter a state called pluripotency but instead occurs through a more direct process called transdifferentiation.

The conversion occurs with relatively high efficiency — generating as many as 50,000 neurons from 1 milliliter of blood — and it can be achieved with fresh or previously frozen and stored blood samples, which vastly enhances opportunities for the study of neurological disorders such as schizophrenia and autism.

A paper describing the findings was published online June 4 in the Proceedings of the National Academy of Sciences.

The resulting human neurons aren’t perfect. They lack the ability to form mature synapses, or connections, with one another. But they are able to carry out the main fundamental functions of neurons.

Erenumab is part of new class of drugs —fully human monoclonal antibodies — that block calcitonin gene-related peptide (CGRP), a molecule that transmits migraine pain signals during an attack. The medication is a long-lasting injection that is meant to stop a migraine before it even starts.

“If we can block CGRP, then we can abort a migraine attack,” said Dr. David Kudrow, director of the California medical clinic for headache, who was not involved in the study.

More than 37 million Americans suffer from migraine attacks, according to the American Headache Society. Of these, about 4 million have chronic migraine and suffer headaches for 10 to 14 days a month.

While some people are helped by low cost, over-the-counter drugs such as ibuprofen, others need stronger prescription medications, such as sumatriptan and ergotamine, which constrict the blood vessels in the brain and can cause dizziness or nausea. Botox injections are also used to help ease migraines in some people.

But a large percentage of sufferers are not helped by anything.

“"This is the first-ever mechanism specific migraine drug designed for prevention," said lead study author Dr. Peter Goadsby, professor of neurology at Kings College London, UK and University of California, San Francisco. "This will change migraine treatment for those who don’t respond to conventional treatments.”

To participate in the study — the results were released ahead of the annual meeting of the American Academy of Neurology — adults ages 18 or over, had to report between four and 14 disabling episodic migraines, or 15 or more chronic migraines per month, and to have failed two or more preventative treatments, such as topiramate, propranolol, or amitriptyline.

Researchers found that the drug reduced the average number of monthly migraine headaches by more than 50 percent for nearly a third of study participants. After three months, patients treated with the human antibody were nearly three times more likely to have reduced their migraine days by 50 percent or more, than those treated with placebo.

They also had a greater average reduction in the number of days with headaches and the number of days they needed to take drugs to stop the migraines.

Ketamine has a reputation as a party drug but is licensed as an anaesthetic.

The study found use of the drug via a nasal spray led to "significant" improvements in depressive symptoms in the first 24 hours.

The Royal College of Psychiatrists said it was a "significant" study that brought the drug "a step closer to being prescribed on the NHS".

The report by researchers from Janssen Research and Development, a Johnson and Johnson company, and Yale School of Medicine, is the first study into ketamine as a treatment for depression that has been done by a drug company.

It is being published in the American Journal of Psychiatry.

The trial looked at 68 people at imminent risk of suicide.

All patients were treated with a stay in hospital and anti-depressants.

In addition, half were given ketamine in the form of esketamine (part of the ketamine molecule) in a nasal spray and half were given a placebo.

The study found those using esketamine had a much greater improvement in depression symptoms at all points over the first four weeks of treatment.

However, at 25 days the effects had levelled out.

The study's authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective.

The nasal spray is now undergoing phase three trials before it can be licensed for treatment.

"A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug–microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance."

In mice, the drug minoxidil changes blood vessel structure, reducing vessel stiffness and increasing blood flow to the brain. The findings pave the way for studies of the drug’s potential as a treatment for older adults and others who have health problems resulting from blood vessel stiffness. Elastic fibers in the walls of large blood vessels enable them to bounce back after being stretched. The diameter of vessels is controlled by both the amount of elastic fibers present and the degree of squeezing from smooth muscle cells in the vessel walls. A larger diameter allows more blood through. As adults age, their blood vessels slowly begin to lose flexibility. The increased vessel stiffness and reduced vessel diameter that result contribute to the aging-related risk of heart attack, stroke, and dementia. There are also rare diseases that can cause lifelong vessel stiffness from insufficient elastic fibers. The dozens of drugs on the market for reducing blood pressure work in very different ways. Minoxidil, which also promotes hair growth when used on the scalp, can relax the smooth muscle cells in blood vessels by opening certain potassium channels. Prior studies with animals suggested that another function of the drug is to turn on the genes for elastin (a protein found in elastic fibers) and other elastic fiber genes, such as Fbn-1 and Lox, causing elastin deposits within the blood vessel wall.

The research team studied mice that were genetically modified to have low levels of elastin in their blood vessels. As a result, the mice had high blood pressure, increased blood vessel stiffness, and reduced blood flow to the brain. One group of modified mice received minoxidil in their drinking water from weaning until 3 months, a second group was treated for only the two weeks before elastin gene studies, and a third group had plain water instead.

The scientists found that minoxidil lowered blood pressure and vessel stiffness to levels similar to healthy mice. Imaging tests showed that vessel diameter and blood flow to the brain increased in the minoxidil-treated mice. One month after the drug was stopped, the diameter was still enlarged, suggesting that the structure of the blood vessel walls had changed. Using protein analyses and tissue studies, the team showed that minoxidil increased elastin deposits in blood vessels. Gene studies revealed that minoxidil revs up not only elastin and elastic fiber genes but also more than 100 other genes related to blood vessel structure.

According to research published this week in the journal The Lancet Infectious Diseases. The study points to a potential new tool to fight malaria: the medication ivermectin. Studies conducted in the 2000s, including one in 2010, show that malaria-carrying mosquitoes die after feeding on individuals who have ingested the drug.

Malaria is a mosquito-borne infection that affects more than 200 million people worldwide. The disease is transmitted when an infected mosquito bites an individual, spreading a parasite called plasmodium. In humans, the parasite can cause fever, headache, chills and even death. Despite years of eradication efforts in developing countries, growing research shows malaria-carrying mosquitoes are becoming resistant to the insecticides meant to wipe them out.

"Since 2015, the number of annual deaths from malaria has stabilized," says Menno Smit, MD, a Ph.D. candidate at the Liverpool School of Tropical Medicine who led the new study. "We're not making any more progress. We need new tools, and ivermectin could be one."

Ivermectin was developed in the early 1980s as a drug to fight parasites that cause river blindness and elephantiasis. Smit and his colleagues hope it can also help eradicate malaria.

In their study, the researchers demonstrate that three high doses of ivermectin make human blood deadly to mosquitoes for up 28 days after the third treatment. This high dose of ivermectin was also well-tolerated with few side effects.

To reach these conclusions, researchers at the Jaramogi Oginga Odinga Teaching and Referral Hospital in Kenya gave 47 participants 600 miligrams of ivermectin in tablet form for three days in a row. Blood samples were obtained from these participants six times and then fed to mosquitoes in cages.

"We put the blood in an artificial membrane that mosquitoes could bite on and then watched," Smit explains. "Most died within a week after [drinking] the blood."

Two weeks after feeding, 97 percent of the mosquitoes had died.

Another group of 48 patients were given a dosage of 300 milligrams but the mosquito death rate was not as high.

Either dose is higher than usual. More than 2.5 billion ivermectin treatments have been distributed since 1987 for the treatment of parasitic infections, typically one annual dose of up to 200 milligrams.

In this study, Smit says the high dosage of 600 milligrams for three days was well-tolerated. Participants reported few side effects, though he admits everyone in the study was already hospitalized and receiving treatment for malaria.

"The patients may have noticed less side effects because they were already feeling sick," Smit explains. "We have yet to see if the excellent tolerance we saw would be just as good in healthy individuals."

Smit adds that the high dose of ivermectin still needs to be tested in children to ensure that it is safe for all ages.

Dr. Peter Hotez, who was not involved in the study and is dean of the National School of Tropical Medicine at the Baylor College of Medicine, says bigger studies need to be done before ivermectin is seriously considered as part of a national malaria control program.

But "I think ivermectin has potential as a supplemental strategy for malaria control and prevention," Hotez wrote in an email to NPR. "The drug has an excellent safety track record from its use in mass drug administration campaigns in Africa."