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Depression, obesity and pain could be treated by targeting one protein

Depression, obesity and chronic pain could all be treated ‘by blocking the SAME protein’

  • Scientists blocked protein FKBP51 for the first time without also affecting others
  • Hope will lead to treatment in humans; FKBP51 is also being tested in cancer
  • FKBP51 has many functions from regulating glucose to stress management 
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Depression, obesity and chronic pain could all be treated by targeting the same protein, research suggests.

A study found blocking the protein FKBP51 in mice relieved chronic pain, boosted their moods and encouraged weight loss.

This is the first time scientists have been able to target this specific protein without also affecting the function of others.

Researchers hope their study will lead to new treatments in humans, with FKBP51 inhibitors also being tested in alcoholism and cancer.  

Depression, obesity and chronic pain could all be treated by targeting the same protein (stock)

The research was carried out by the Technical University of Darmstadt, Germany, and led by Dr Felix Hausch, a professor of structure-based drug discovery. 

‘The FKBP51 protein plays an important role in depression, obesity, diabetes and chronic pain states,’ Dr Hausch said.

‘We developed the first highly potent, highly selective FKBP51 inhibitor, called SAFit2, which is now being tested in mice. 

‘Inhibition of FKBP51 could thus be a new therapeutic option to treat all of these conditions.’  

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FKBP51 is expressed throughout the body, including in the brain, skeletal muscle tissue and fat.

It also has multiple roles, from regulating the uptake of glucose to managing stress.

This led the researchers to believe FKBP51 may be involved in the onset of numerous conditions. 

‘I was intrigued by the peculiar regulatory role it seemed to play in cells,’ Dr Hausch said.


While it is normal to feel down from time to time, people with depression may feel persistently unhappy for weeks or months on end.

Depression can affect anyone at any age and is fairly common – approximately one in ten people are likely to experience it at some point in their life. 

Depression is a genuine health condition which people cannot just ignore or ‘snap out of it’.

Symptoms and effects vary, but can include constantly feeling upset or hopeless, or losing interest in things you used to enjoy.

It can also cause physical symptoms such as problems sleeping, tiredness, having a low appetite or sex drive, and even feeling physical pain.

In extreme cases it can lead to suicidal thoughts.

Traumatic events can trigger it, and people with a family history may be more at risk.

It is important to see a doctor if you think you or someone you know has depression, as it can be managed with lifestyle changes, therapy or medication. 

Source: NHS Choices 

‘And there was a known natural product that could serve as a starting point. 

‘Collectively, this looked like an interesting protein to work on.’ 

The difficulty was FKBP51 looks a lot like its ‘protein cousin’ FKBP52.

‘These two proteins are very similar in structure, but they are doing opposing things in cells,’ Dr Hausch said.

‘We have this yin-yang situation. 

‘Selectivity between these two proteins is thought to be crucial, but this is hard to achieve since the two proteins are so similar. 

‘We discovered FKBP51 can change its shape in a way FKBP52 can’t and this allowed the development of highly selective inhibitors.’ 

When mice were treated with SAFit2 – the lead FKBP51-inhibitor – they experienced less stress.

The animals were also less likely to gain weight, which is thought to be due to them having a reduced appetite.

And they had normal glucose levels and reduced pain as a result of treatment.

Full results will be presented at the American Chemical Society Spring 2019 conference in Orlando later today. 

But Dr Hausch added much more needs to be done before SAFit2 can be used in humans.

His team is also investigating FKBP51’s role in cancer after tests revealed certain glioblastoma tumours overexpress the protein.

They hope FKBP51 inhibitors could be used when a patient’s tumour has mutated beyond what can be treated with existing cancer drugs.

‘We may be able to resensitise them to different types of chemotherapy using these specific inhibitors,’ Dr Hausch said.   


Obesity is defined as an adult having a BMI of 30 or over.

A healthy person’s BMI – calculated by dividing weight in kg by height in metres, and the answer by the height again – is between 18.5 and 24.9. 

Among children, obesity is defined as being in the 95th percentile.

Percentiles compare youngsters to others their same age. 

For example, if a three-month-old is in the 40th percentile for weight, that means that 40 per cent of three-month-olds weigh the same or less than that baby.

Around 58 per cent of women and 68 per cent of men in the UK are overweight or obese. 

The condition costs the NHS around £6.1billion, out of its approximate £124.7 billion budget, every year.

This is due to obesity increasing a person’s risk of a number of life-threatening conditions.

Such conditions include type 2 diabetes, which can cause kidney disease, blindness and even limb amputations.

Research suggests that at least one in six hospital beds in the UK are taken up by a diabetes patient.

Obesity also raises the risk of heart disease, which kills 315,000 people every year in the UK – making it the number one cause of death.

Carrying dangerous amounts of weight has also been linked to 12 different cancers. 

This includes breast, which affects one in eight women at some point in their lives.

Among children, research suggests that 70 per cent of obese youngsters have high blood pressure or raised cholesterol, which puts them at risk of heart disease.

Obese children are also significantly more likely to become obese adults. 

And if children are overweight, their obesity in adulthood is often more severe.  

As many as one in five children start school in the UK being overweight or obese, which rises to one in three by the time they turn 10.  

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