Walking restored in paralysed mice with spinal injury

Agencies
July 23, 2018

Boston, Jul 23: Scientists have successfully restored the ability to walk in mice that were paralysed after a spinal cord injury, an advance that may pave the way for similar treatments in humans.

Most people with spinal cord injury are paralysed from the injury site down, even when the cord is not completely severed.

Researchers at Boston Children's Hospital in the US provided insight into why the spared portions of the spinal cord do not keep working.

They also show that a small-molecule compound, given systemically, can revive these circuits in paralysed mice, restoring their ability to walk.

"For this fairly severe type of spinal cord injury, this is most significant functional recovery we know of. We saw 80 per cent of mice treated with this compound recover their stepping ability," said Zhigang He, from Boston Children's Hospital.

Many animal studies looking to repair spinal cord damage have focused on getting nerve fibres, or axons, to regenerate, or to getting new axons to sprout from healthy ones.

While impressive axon regeneration and sprouting have been achieved their impacts on the animals' motor function after a severe injury are less clear.

Some studies have tried using neuromodulators such as serotonergic drugs to simulate the spinal circuits, but have gotten only transient, uncontrolled limb movement.

Researchers took another approach, inspired by the success of epidural electrical stimulation-based strategies, the only treatment known to be effective in patients with spinal cord injury.

This treatment applies a current to the lower portion of the spinal cord; combined with rehabilitation training, it has enabled some patients to regain movement.

"Epidural stimulation seems to affect the excitability of neurons," said He.

"However, in these studies, when you turn off the stimulation, the effect is gone. We tried to come up with a pharmacologic approach to mimic the stimulation and better understand how it works," he said.

Researchers selected a handful of compounds that are already known to alter the excitability of neurons, and are able to cross the blood-brain barrier.

They gave each compound to paralysed mice in groups of 10 via intraperitoneal injection.

All mice had severe spinal cord injury, but with some nerves intact. Each group (plus a control group given a placebo) was treated for eight to ten weeks.

One compound, called CLP290, had the most potent effect, enabling paralysed mice to regain stepping ability after four to five weeks of treatment. Electromyography recordings showed that the two relevant groups of hind-limb muscles were active.

The animals' walking scores remained higher than the controls' up to two weeks after stopping treatment. Side effects were minimal.

"We are very excited by this direction. We want to test this kind of treatment in a more clinically relevant model of spinal cord injury," said He.

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Agencies
June 27,2020

After admitting that the world may have a COVID-19 vaccine within one year or even a few months earlier, the World Health Organisation (WHO) on Friday said that UK-based AstraZeneca is leading the vaccine race while US-based pharmaceutical major Moderna is not far behind.

WHO Chief Scientist Soumya Swaminathan stated that the AstraZeneca's coronavirus vaccine candidate is the most advanced vaccine currently in terms of development.

"I think AstraZeneca certainly has a more global scope at the moment in terms of where they are doing and planning their vaccine trials," she told the media.

AstraZeneca's Covid-19 vaccine candidate developed by researchers from the Oxford University will likely provide protection against the disease for one year, the British drug maker's CEO told Belgian radio station Bel RTL this month.

The Oxford University last month announced the start of a Phase II/III UK trial of the vaccine, named AZD1222 (formerly known as ChAdOx1 nCoV-19), in about 10,000 adult volunteers. Other late-stage trials are due to begin in a number of countries.

Last week, Swaminathan had said that nearly 2 billion doses of the COVID-19 vaccine would be ready by the end of next year.

Addressing the media from Geneva, she said that "at the moment, we do not have a proven vaccine but if we are lucky, there will be one or two successful candidates before the end of this year" and 2 billion doses by the end of next year.

Scientists predict that the world may have a COVID-19 vaccine within one year or even a few months earlier, said the Director-General of the World Health Organization even as he underlined the importance of global cooperation to develop, manufacture and distribute the vaccines.

However, making the vaccine available and distributing it to all will be a challenge and will require political will, WHO chief Tedros Adhanom Ghebreyesus said on Thursday during a meeting with the European Parliament's Committee for Environment, Public Health and Food Safety.

One option would be to give the vaccine only to those who are most vulnerable to the virus.

There are currently over 100 COVID-19 vaccine candidates in various stages of development.

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Agencies
May 19,2020

New York, May 19: Cigarette smoke spurs the lungs to make more of the receptor protein which the novel coronavirus uses to enter human cells, according to a study which suggests that quitting smoking might reduce the risk of a severe coronavirus infection.

The findings, published in the journal Developmental Cell, may explain why smokers appear to be particularly vulnerable to severe COVID-19 disease.

"Our results provide a clue as to why smokers who develop COVID-19 tend to have poor clinical outcomes," said study senior author Jason Sheltzer, a cancer geneticist at Cold Spring Harbor Laboratory in the US.

"We found that smoking caused a significant increase in the expression of ACE2, the protein that SARS-CoV-2 uses to enter human cells," Sheltzer said.

According to the scientists, quitting smoking might reduce the risk of a severe coronavirus infection.

They said most individuals infected with the virus suffer only mild illness, if they experience any at all.

However, some require intensive care when the sometimes-fatal virus attacks, the researchers said.

In particular, they said three groups have been significantly more likely than others to develop severe illness -- men, the elderly, and smokers.

Turning to previously published data for possible explanations for these disparities, the scientists assessed if vulnerable groups share some key features related to the human proteins that the coronavirus relies on for infection.

First, they said, they focused on comparing gene activity in the lungs across different ages, between the sexes, and between smokers and nonsmokers.

The scientists said both mice that had been exposed to smoke in a laboratory, and humans who were current smokers had significant upregulation of ACE2.

According to Sheltzer, smokers produced 30-55 per cent more ACE2 than their non-smoking counterparts.

While the researchers found no evidence that age or sex impacts ACE2 levels in the lungs, they said the influence of smoke exposure was surprisingly strong.

However, they said, the change seemed to be temporary.

According to the data, the level of the receptors ACE2 in the lungs of people who had quit smoking was similar to that of non-smokers.

The study noted that the most prolific producers of ACE2 in the airways are mucus-producing cells called goblet cells.

Smoking is known to increase the prevalence of such cells, the scientists said.

"Goblet cells produce mucous to protect the respiratory tract from inhaled irritants. Thus, the increased expression of ACE2 in smokers' lungs could be a byproduct of smoking-induced secretory cell hyperplasia," Sheltzer explained.

However, Sheltzer said other studies on the effects of cigarette smoke have shown mixed results.

"Cigarette smoke contains hundreds of different chemicals. It's possible that certain ingredients like nicotine have a different effect than whole smoke does," he said.

The researchers cautioned that the actual ACE2 protein may be regulated in ways not addressed in the current study.

"One could imagine that having more cells that express ACE2 could make it easier for SARS-CoV-2 to spread in someone's lungs, but there is still a lot more we need to explore," Sheltzer said.

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Agencies
February 23,2020

Los Angeles, Feb 23: According to researchers, if administered quickly, a common medication that reduces bleeding could be a treatment for bleeding stroke.

The Spot Sign and Tranexamic Acid on Preventing ICH Growth - Australasia Trial (STOP-AUST) was a multicenter, prospective, randomized, double-blind, placebo-controlled, phase 2 clinical trial using the antifibrinolytic agent tranexamic acid in people with intracerebral hemorrhage (ICH).

ICH is a severe form of acute stroke with few treatment options.

Tranexamic acid is currently used to treat or prevent excessive blood loss from trauma, surgery, tooth removal, nosebleeds and heavy menstruation. For this study, one hundred patients with active brain bleeding were given either intravenous tranexamic acid or placebo within 4.5 hours of symptom onset.

Researchers analyzed brain CT scans taken during the 24-hour period after treatment with tranexamic acid or placebo.

Researchers found a trend towards reduced hemorrhage expansion in the group treated with tranexamic acid, especially in those treated within 3 hours of the brain bleed. However, this trend was not statistically significant. The finding was consistent with previous research using the medication.

"Further trials using tranexamic acid are ongoing and focusing on ultra-early treatment - within 2 hours. 

This is where the greatest opportunity for intervention appears to be. Tranexamic acid is inexpensive, safe and widely available. Our results and others provide great impetus for further, focused research using this treatment," Nawaf Yassi said.

Larger trials focused on patient outcomes are required for this therapy to enter routine clinical practice.

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