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'Bionic' spinal implant helped paralysed rats walk

"Elastic implant 'restores movement' in paralysed rats," BBC News reports after researchers developed an implant that can be used to treat damaged spinal cords in rats.

The spinal cord, which is present in all mammals, is a bundle of nerves that runs from the brain through the spine, before branching off to different parts of the body.

It is the main "communication route" the brain uses to control the body, so damage usually results in some degree of paralysis or sensory loss, depending on the extent of the injury.

This promising research developed a novel spinal cord implant that has been able to restore movement in paralysed rats. The implant is made of a flexible material that is able to integrate and move with the spinal cord.

This overcomes problems found with previously tested rigid and inflexible implants, which have caused inflammation and quickly stopped working.

The implant works by delivering both electrical and chemical signals, and enabled the rats to walk again for the six weeks of testing.

However, the research is mainly "proof of concept" at this stage, showing the technique works in animals – at least in the short term. It remains to be seen whether implants are safe and effective at restoring movement in people with paralysis. 

 

Where did the story come from?

The study was carried out by researchers from École Polytechnique Fédérale de Lausanne in Switzerland and other institutions in Switzerland, Russia, Italy and the US.

Financial support was provided by various organisations, including the Bertarelli Foundation, the International Paraplegic Foundation, and the European Research Council.

It was published in the peer-reviewed journal, Science Magazine. 

Of all the UK coverage, BBC News reported the research most accurately, and included quotes about the promising nature of the research, but also due caution about the long timeline ahead before it is known whether such implants could be used in people.

Other headlines, such as that in The Times, arguably offer premature hope of a new treatment that can help the paralysed walk again. 

 

What kind of research was this?

This animal research aimed to develop a new flexible spinal implant to restore movement after a spinal cord injury.

Implants are just one of the ways medical science is exploring how to help people who have spine injuries regain sensation and movement.

In the past, electrical implants for the spinal cord encountered problems because spinal cord tissue is soft and flexible, while the implants of old were often rigid and inflexible.

The researchers expected implants with mechanical properties matching those of the host tissue would work better and for longer.

Here, they designed and developed a new soft electrical implant, which has the shape and elasticity of the dura mater, the outermost layer of the protective membranes (meninges) that cover the brain and spinal cord.

The device was tested in paralysed rats. Animal studies are a valuable first step in the development of treatments that may one day be used in people.

However, the road ahead is a long one in terms of developing the treatment for testing in people, hopefully followed by trials of its safety and effectiveness.

 

What did the research involve?

The researchers developed a silicone implant they called electronic dura mater, or e-dura. This implant has interconnecting channels that transmit electrical signals and can also deliver drugs. It was made for surgical insertion just beneath the dura mater layer.

They first tested the long-term functionality of this soft implant compared with conventional stiff implants. Long-term meant testing the device for six weeks.

Each type of implant was inserted into the lower part of the spinal cord of healthy rats. The rats were then assessed using specialised movement recordings, and the rats with the soft spinal implant were able to behave and move as normal.

However, rats with the stiff implants started to demonstrate problems with their movement one to two weeks after surgery, which only deteriorated further up to six weeks.

When examining the rats' spinal cords after the implants were removed at six weeks, the researchers found rats with the stiff implants displayed significant deformity and inflammation in the spinal cord. None of these adverse effects were observed in those who had the soft implant.

They followed this with a series of further tests of the mechanics and functioning of the soft implant, both in the laboratory using a model of spinal cord tissue and in further tests in healthy rats.

The researchers also examined the ability of e-dura to restore movement after spinal cord injury.

The rats received a spinal cord injury that led to permanent paralysis of both hind legs. The e-dura implant was then surgically inserted in the spinal cord, and drug therapy and electrical stimulation were delivered through the electrode to see how it worked. 

 

What were the basic results?

Most of the results in the publication relate to the initial developmental stages of the device. When it came to the paralysed rats, relatively little was said.

However, what the researchers did say is the combination of electrical and chemical stimulation through the implant enabled the paralysed rats to move both of their hind legs again and walk, apparently as normal (though this isn't specifically stated).

The e-dura implant was able to bring about these effects for the six-week period it was tested. 

 

How did the researchers interpret the results?

The researchers concluded they have developed a soft implant that shows long-term biointegration and functioning with the spinal cord.

The implants met the demanding mechanical properties of the spinal tissue, with a limited inflammatory reaction that has been seen with other implants.

When used in paralysed rats, the implant allowed for electrical and chemical stimulation to restore movement deficits over an extended period of time.

 

Conclusion

This is promising research that demonstrates how a new spinal cord implant has been able to restore movement in paralysed rats.

The e-dura implant is a breakthrough in that it overcomes a lot of the problems presented by previous rigid and inflexible implants. Instead, it is made of a flexible material that is able to integrate with spinal cord tissue.

The study demonstrated long-term functionality in rats and few side effects over the six-week testing period.

Rats given a serious spinal cord injury, who were consequently permanently paralysed, were able to walk again after the implant was surgically placed in their spinal cord. The implant works by delivering both electrical and chemical signals.

However, this research is still in the very early stages. While the findings are promising, there is a long way to go before we know whether these implants can be developed to successfully help humans with spinal injuries.

If the implants were developed for human testing, they would need to go through several stages of safety and effectiveness testing to see whether they worked at restoring movement in paralysed people.

It also needs to be seen how they would function in the much longer term, beyond just a few weeks.

Loss of movement is only one of the ways a person can be affected by permanent paralysis of both legs.

We do not know whether this implant would have any effect on loss of bladder, bowel or sexual function, for example.

These effects can have as much of a detrimental effect on quality of life as loss of physical movement.

But, overall, this is promising early-stage research and future developments are awaited with anticipation.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Elastic implant 'restores movement' in paralysed rats. BBC News, January 9 2015

'Cyborg' spinal implant could help paralysed walk again. The Daily Telegraph, January 8 2015

The tiny ribbon that could help the paralysed walk again: 'Cyborg' implant can delivers electric shocks and drugs directly to the spine and even read brain activity. Mail Online, January 9 2015

Links To Science

Minev IR, Musienko P, Hirsch A, et al. Electronic dura mater for long-term multimodal neural interfaces. Science. Published online January 9 2015

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Out of character criminal actions linked to dementia

“Could criminal behaviour be the first sign of dementia?” the Mail Online asks. A US study found an association between sudden, unusual criminal behaviour, such as shoplifting or urinating in public, and various types of dementia.

The study looked at crimes committed by patients suffering from a number of diseases that damage the brain and cause dementia. It found more than 8% of patients had a history of criminal behaviour that first emerged during their illness.

Patients with Alzheimer’s disease, a common form of dementia – were the least likely to commit crimes, while those with a type of uncommon dementia called frontotemporal dementia (FTD) were the most likely to commit crimes including theft, traffic violations, sexual advances and urinating in public. This has long been recognised as an effect of the disorder, as it typically causes a change in personality and can lead to disinhibition.

This study suggests – but cannot prove – that, in older adults, new criminal behaviour could be a sign of brain damage caused by a dementing disorder.

If you are worried about a relative’s behaviour or changes in personality, it is sensible to seek medical advice.

 

Where did the story come from?

The study was carried out by researchers from Lund University in Sweden, the University of California, and the University of Notre Dame in Australia.

It was funded by the Hennerlöfska Foundation for Medical Research, The Swedish Society of Medicine and the Trolle-Wachtmeister Foundation for Medical Research in Sweden, and the National Institutes of Health (NIH), the Consortium for Frontotemporal Dementia Research, the Tau Consortium and the Hillblom Aging Network in the US.

The study was published in the peer-reviewed medical journal JAMA Neurology.

The Mail’s coverage was accurate but uncritical. Its photos of someone handcuffed and an angry-looking older person were unnecessary.

 

What kind of research was this?

This was a retrospective study of patients seen at a memory and ageing centre in the US. It was designed to look at the frequency and type of criminal behaviour that occurred among those diagnosed with a dementing disorder.

Such neurodegenerative diseases can cause brain dysfunction in areas such as judgement, executive function, emotional processing, sexual behaviour, violence and self-awareness, and this can result in antisocial and criminal behaviour.

The crimes committed by people with dementia range from theft, traffic violations and violence to hypersexuality and homicide (but the latter is thought to be rare). The researchers wanted to quantify how often this happens and the extent to which this was the event that led the person to being diagnosed with a form of dementia.

 

What did the research involve?

Researchers reviewed the medical records of 2,397 patients seen at a US memory and ageing centre between 1999 and 2012. These patients had been diagnosed with a variety of neurodegenerative disorders that can cause dementia.

The researchers screened the patients’ medical notes for specific key words to identify criminal behaviour. Keywords were chosen to represent all the criminal behaviours that have been observed in people with dementia. These included court, arrest, criminal, detain, steal, speeding, violation and violence.

The types of criminal behaviour were then stratified according to the following categories:

  • driving under the influence (aka drink driving)
  • hit and run
  • traffic violations
  • speeding
  • insubordination towards legal authorities
  • sexual advances
  • loitering
  • public urination
  • theft
  • trespassing
  • violence (including physical and verbal threats)

Only criminal behaviours that occurred during the patient’s illness were included. The criminal behaviour was considered to be the presenting symptom if the doctor specifically indicated this in the medical record.

Researchers then calculated the frequency of criminal behaviour for the following categories of dementia or dementia-like conditions:

  • Alzheimer’s disease
  • frontotemporal dementia
  • semantic variant of primary progressive aphasia – a type of dementia that effects language and communication, such as speaking, reading and understanding
  • Huntington’s disease – a genetic condition that can cause dementia-like symptoms
  • vascular dementia – dementia caused by reduced blood flow to the brain

 

What were the basic results?

Of the 2,397 patients studied, 204 (8.5%) had a history of criminal behaviour that emerged during their illness.

Of the major diagnostic groups, the following proportions exhibited criminal behaviour:

  • 42 of 545 people (7.7%) with Alzheimer’s disease
  • 64 of 171 people (37.4%) with FTD
  • 24 of 89 people (27.0%) with the semantic variant of primary progressive aphasia
  • six of 30 people (20%) with Huntington’s disease 
  • nine of 61 people (14.8%) with vascular dementia

Criminal behaviour was one of the symptoms that caused 14% of people to be diagnosed with FTD, compared with 2% of patients with Alzheimer’s disease. Of those diagnosed with FTD, 6.4% were more likely to have exhibited violence in this criminal behaviour compared with 2% of people with Alzheimer’s.

Common types of criminal behaviour in the FTD group included theft, traffic violations, sexual advances, trespassing and public urination. In the Alzheimer’s group, the most common crime was traffic violations, often related to memory loss.

 

How did the researchers interpret the results?

The researchers point out that new criminal behaviours are associated with specific dementing disorders such as FTD, but not with others.

"The findings from this study suggest that individuals who care for middle-aged and elderly patients need to be vigilant in the diagnosis of degenerative conditions when behaviour begins to deviate from the patient's norm, and work hard to protect these individuals when they end up in legal settings," they concluded.

 

Conclusion

This study looks at an important issue, but it had several limitations that make the results less reliable:

  • It used data on criminal behaviour taken from patients’ medical notes rather than relying on official criminal records.
  • Patients referred to the centre may have had more behavioural problems than those with dementia in the general population.
  • The study cannot show the criminal behaviour was caused by dementia.
  • The study had no control group, so cannot compare crime rates among healthy adults with those with dementia.

Dementia can lead to changes in behaviour and, in some people, loss of inhibition and aggression.

However, it’s important that people with dementia are not labelled as potential criminals and it should be noted that most are more of a danger to themselves then others.

If you are worried about a relative’s behaviour or changes in personality, it is sensible to seek medical advice.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Could criminal behaviour be the first sign of DEMENTIA? Offending for the first time in old age may be due to brain damage. Mail Online, December 6 2015

Links To Science

Lijegren M, Naasan G, Temlett J, et al. Criminal Behavior in Frontotemporal Dementia and Alzheimer Disease. JAMA Neurology. Published online January 5 2015

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Could meal-in-a-pill 'trick' body into losing weight?

“Weight loss drug fools body into reacting as if it has just eaten,” The Guardian reports. The drug, fexaramine (or Fex), stimulates a protein involved in metabolism that is usually activated when the body begins eating, though it has only been tested in mice.

Researchers found that obese mice given Fex stayed the same weight despite continuing to eat the same amount of a high-fat diet. However, unlike some media claims, they did not actually lose any weight. It had no effect on mice of normal weight.

The protein that is stimulated, FXR (farnesoid X receptor), is present in many organs of the body and plays a complex role in metabolism that is not fully understood. 

Previous drugs developed to activate this protein have shown conflicting results, possibly because they entered the bloodstream and so acted on all of the organs. Fex has been developed so that it appears to be barely absorbed into the blood stream, and so only acts on the FXR in the intestines. This provided better results for obese mice and also reduces the risk of side effects.

Further animal and primate studies will need to be conducted before the drug would be allowed to progress to human trials, but these are promising results. However, even if these trials passed with flying colours, we would estimate that it would take at least 5-10 years before any drug based on this research came to market.

 

Where did the story come from?

The study was carried out by researchers from the Salk Institute for Biological Studies in California and several other institutes in the US, Australia and Switzerland. It was funded by the US National Institutes of Health, the Glen Foundation for Medical Research, the Leona M. and Harry B. Helmsley Charitable Trust, Ipsen/Biomeasure, the California Institute for Regenerative Medicine, the Ellison Medical Foundation, the National Health and Medical Research Council of Australia, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A financial conflict of interest was reported. Many of the contributing authors “are co-inventors of FXR molecules and methods of use, and may be entitled to royalties from their use”.

The study was published in the peer-reviewed journal Nature Medicine.

In general, the media have reported the story accurately, pointing out that it is in the early stages of development and that it has only been tested on mice. However, as mentioned, headlines such as the Daily Mirror’s “'Imaginary meal' diet pill tricks body into losing weight”, or The Daily Telegraph’s assertion that the “pill makes you feel full” are inaccurate. None of the mice lost weight and none of their appetites were suppressed.

 

What kind of research was this?

This was an animal study to test whether a new drug could improve the metabolism of mice. The researchers conducted a variety of experiments of the drug, comparing their response with mice receiving a placebo.

The drug was created to mimic an effect of eating food. Food causes bile acids to be secreted and this activates a protein called FXR (farnesoid X receptor).

FXR plays a complex role in metabolism that is not fully understood. It is present in many organs of the body, including the kidney, stomach, intestines, gall bladder, liver and both white and brown fat cells.

Previously, drugs have been developed to activate FXR, but they have encountered problems because of activating FXR in all of the organs. This gave conflicting outcomes. For example, mice of normal weight given these drugs had improved glucose tolerance, whereas obese mice put on more weight and had even poorer glucose tolerance. It was not clear why this happened, so the researchers wanted to investigate whether just activating FXR in the intestines improved metabolism.

They developed Fex to activate the intestinal FXR drug instead of food, without it being absorbed into the general circulation, to see if this made a difference. They also say that limiting absorption means there would be less potential for side effects.

 

What did the research involve?

The researchers developed a drug called Fex and performed a number of tests using mice.

They first tested the absorption of Fex into the general circulation. They gave mice either a Fex pill by mouth or an injection of Fex into the fluid that surrounds the abdominal organs. The researchers then measured the level of FXR activation in each organ.

The researchers then gave normal weight mice either a Fex pill or a placebo for 35 days. They then compared their weight, metabolic rate and sensitivity to insulin.

Lastly, mice were fed a high-fat diet (60% fat) for 14 weeks to make them obese. The researchers then gave them different doses of the Fex pill or a placebo for five weeks. They compared their weight, metabolic rate, extent of unhealthy white fat and healthy brown fat, and markers of tissue inflammation.

 

What were the basic results?

The oral Fex pill activated FXR in the intestine and did not activate it in the liver or kidneys. The researchers say this shows that it was only minimally absorbed into the general circulation. This was in comparison to the injection of Fex into the abdominal cavity, which stimulated FXR in the intestine as well as the liver and kidneys.

There was no difference between normal weight mice given oral Fex for five weeks in terms of weight gain (small amount) and other metabolic measurements, compared to normal weight mice given placebo.

In obese mice, the Fex pill caused an improvement in metabolism compared to placebo, including:

  • reduced weight gain
  • increased sensitivity to insulin
  • more unhealthy white fat turning into healthy brown fat
  • reduced inflammation

These obese mice were 34 grams at the start of the experiment (normal weight mice would be around 28 grams). They continued on the high-fat diet (60% fat) for five weeks. Those given placebo increased in weight to 44 grams, but those given the highest dose of Fex did not gain any more weight. None of these mice lost weight. The researchers report that there was no change in appetite or food consumption between the mice given Fex and those given placebo.

 

How did the researchers interpret the results?

The researchers concluded that Fex might be a “promising” approach to stimulating FXR, in order to improve metabolism. The say that the “absence of a change in food intake is notable, as failure of appetite control is a major reason for weight gain”. They say that, as this drug appears to improve metabolism without any change in food intake, it “may offer a viable alternative for obesity treatments”. They also point out that as Fex is only minimally absorbed and only stimulates the intestinal FXR, it offers “improved safety profiles” by not circulating around the whole of the body.

 

Conclusion

This animal study has shown that a new drug called Fex prevents obese mice from further weight gain, despite remaining on a high-fat diet. There were also other metabolic improvements, including improved sensitivity to insulin and a reduction of unhealthy white fat cells. There were no differences in measures of metabolism between mice of normal weight given Fex or placebo, although both groups gained a small amount of weight.

This preliminary study appears to show that, unlike previous drugs that have stimulated FXR from the general circulation and shown conflicting results, by targeting intestinal FXR, obese mice benefit. As it has only been tested in mice for five weeks, there is limited information on what these side effects might be in humans.

Further animal and primate studies will need to be conducted before the drug would progress to human trials, but these are promising results.

As the drug appears to improve metabolic function rather than promote weight loss, it could be a candidate to treat diseases of the metabolism, such as type 2 diabetes or metabolic syndrome (where a person has a combination of diabetes, high blood pressure and obesity).

Due to the length of time it takes to bring a drug to market, as well as the chance of a drug proving to be ineffective or unsafe in humans, we can’t envisage Fex (or a variant) appearing in your local pharmacy anytime soon.

In the meantime, tips to help you lose weight can be found here and you can get online support here.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Weight loss drug fools body into reacting as if it has just eaten. The Guardian, January 5 2015

Could an 'imaginary meal' pill solve the obesity crisis? Drug tricks the body into feeling full - AND lowers cholesterol and blood sugar. Mail Online, January 5 2015

Diet pill that makes you feel full proven to keep weight off in mice, scientists say. The Independent, January 5 2015

'Imaginary meal' diet pill tricks body into losing weight. Daily Mirror, January 5 2015

'Imaginary meal' pill makes you feel full and burns fat. The Daily Telegraph, January 5 2015

An 'imaginary meal' pill to lose weight? Scientists reveal latest weapon to battle obesity. Daily Express, January 5 2015

Links To Science

Fang S, Suh JM, Reilly SM, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nature Medicine. Published online January 5 2015

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FactCheck: how does A&E in England compare to other countries?

Is the coalition to blame for England's A&E woes? How do things look in the rest of the UK - and the rest of the world? READ MORE