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Research

New hope in treatment of brain cancer GBM

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Findings from pioneering new research suggest there could be a new approach to treating one of the most common and devastating forms of brain cancer in adults – Glioblastoma Multiforme (GBM). 

In a seven-year study, scientists from the University of Surrey show that a short chain of amino acids (the HTL-001 peptide) is effective at targeting and inhibiting the function of a family of genes responsible for the growth of GBM – Hox genes. The study was conducted in cell and animal models.

The HTL-001 peptide used in the study has undergone safety testing and is suitable for patient trials. These trials are now being considered in GBM and other cancers.

The study adds further progress and gives new hope in an area where advances have not been as rapid as in other cancer types. 

Professor Hardev Pandha, project lead and Professor of Medical Oncology at the University of Surrey, said: “People who suffer from GBM have a five per cent survival rate over a five-year period – a figure that has not improved in decades. 

“While we are still early in the process, our seven-year project offers a glimmer of hope for finding a solution to Hox gene dysregulation, which is associated with the growth of GBM and other cancers, and which has proven to be elusive as a target for so many years.”

Ironically, Hox genes are responsible for the healthy growth of brain tissue but are ordinarily silenced at birth after vigorous activity in the growing embryo. 

However, if they are inappropriately ‘switched on’ again, their activity can lead to the progression of cancer. Hox gene dysregulation has long been recognised in GBM.

The project was carried out in collaboration with the universities of Surrey, Leeds and Texas, and HOX Therapeutics, a University of Surrey start-up company based on the University’s Surrey Research Park.

Professor Susan Short, co-author of the study from the University of Leeds, said: “We desperately need new treatment avenues for these aggressive brain tumours. 

“Targeting developmental genes like the HOX genes that are abnormally switched on in the tumour cells could be a novel and effective way to stop glioblastomas growing and becoming life-threatening.”

James Culverwell, CEO of HOX Therapeutics, said: “HOX Therapeutics is excited to be associated with this project and we hope that with our continuing support, this research will eventually lead to novel and effective treatments for both brain and other cancers where HOX gene over-expression is a clear therapeutic target.”

Research

Brain cancer research backed by award

Dr Sharel Peisan E’s research into nanoscale electrochemistry of brain cancer cells has received the Springboard Award

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Pioneering brain cancer research has been backed by a new six-figure award, to support its ambition to advance diagnosis and treatments. 

Dr Sharel Peisan E, a chemistry lecturer at Teesside University, will examine the nanoscale electrochemistry of brain cancer cells.

Using a multifunctional nanoscale electrochemical imaging platform, Dr E will be able to take a closer look at brain tumour cells and their processes to gain a better understanding of their biology.

The technology uses tiny electrodes to gain an extremely close and detailed visualisation of the biology of living cells.

This research project, backed by an award of £100,000, aims to explore how brain cancer reacts to different therapies on a cellular level, which will be applied to improving or designing more effective treatments for cancer patients.

It will also be able to provide insight into other neurodegenerative diseases such as Alzheimer’s in much the same way.

Glioblastoma is one of the most devastating cancers, although its biology remains somewhat of a mystery in cancer research, with brain cancer cells being difficult to analyse using current methods of examination,” explained Dr E, who is based at Teesside University’s National Horizons Centre.

NHC National Horizons Centre

“My research will use advanced nanoscale imaging to provide a new view of the solid, liquid and gaseous processes, known as heterogeneous processes, on the cancer cells at the nanoscale, providing additional information on the glioblastoma biology which has previously been unattainable through microscopic techniques, allowing us to improve current diagnostics and treatments.”

Dr E won the grant from the Academy of Medical Sciences as part of the Springboard Award, which provides funding and career support for innovative bioscientists.

Teesside University’s National Horizons Centre, based at the Darlington campus, is a £22.3million centre of excellence for innovation and training in biosciences and healthcare, with strength in cancer research.

Professor Vikki Rand, interim director of the National Horizons Centre, said: “Here at the National Horizons Centre, we are positioned at the forefront of the biosciences and healthcare sector, leading groundbreaking research to drive progress in key areas including disease and climate change.

“We are devoted to gaining as much knowledge about cancer as we can, and our work in cancer research is particularly impressive, directly influencing the wider healthcare sector through studies which inform new and improved therapies to help real patients which is, after all, what our research is all about.

“Grants such as the Springboard Award from the Academy of Medical Sciences are extremely important and we are thrilled that Dr E has won this very substantial funding for her research.”

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Research

Research could pioneer new brain haemorrhage treatment

The study could yield a breakthrough to reduce the risk of brain damage and disability and increase patients’ chances of survival

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A novel method is being pioneered for the treatment of brain haemorrhage, which it is hoped could reduce the risk of brain damage and disability and increase patients’ chances of survival.

Brain haemorrhages, or haemorrhagic strokes, occur when blood leaks from a blood vessel in or around the brain and in the UK accounts for about 15 per cent of all strokes.

The reaction of the brain to the sudden presence of excess blood can lead to brain damage, disability and death – with almost a half of patients going on to die within a month as a result of suffering a brain haemorrhage.

Researchers at Nottingham Trent University are now collaborating with the University of Manchester to find a way to prevent the damage to brain cells caused by iron from the blood that builds up in the brain after a haemorrhage.

“The death rates due to brain haemorrhage have not changed for several decades. This sort of research is therefore vital to find the new treatments necessary to improve survival,” said Professor Stuart Allan of the University of Manchester. 

The researchers – funded by Brain Research UK – are focusing on drugs called ‘iron chelators’, which bind to iron to prevent its accumulation in the body.

They will package these iron chelator drugs into bubbles (‘liposomes’) which can be used to more effectively deliver drugs into the body.

It can be challenging to target drugs to affected areas of the brain due to the ‘blood brain barrier’, which works to prevent potentially harmful toxins in the body from reaching it.

But the team hopes its novel approach will enable the drug to stay in the blood stream for a longer period of time and allow enough drug to get to the area of the brain that contains the bleeding, while also not exposing the rest of the body to unnecessary side effects.

The work, which will involve the use of mice and patient samples, will take about three years.

The study involves a multidisciplinary team of scientists led by Nottingham Trent University’s Dr Zahraa Al-Ahmady, in collaboration with Prof Stuart Allan, Dr Adrian-Parry Jones and Dr Ben Dickie at the University of Manchester and NTU’s Prof Sergio Rutella and Prof Graham Ball.

“Unfortunately, no specific medications currently exist to prevent or treat brain haemorrhage,” said lead researcher Dr Al-Ahmady.

“There are severe issues related to having this blood and iron accumulation in the brain, which contributes to the death of brain cells. 

“We hope our approach will prevent this excess iron from damaging neurons and other tissue and be a new approach to blocking blood induced brain damage after bleeding.

“Many of those who suffer a brain haemorrhage will sadly die and those who survive can have permanent disabilities and so the creation of new drugs is essential. 

“We are aiming to find a way to enable treatment to better infiltrate the brain and to remain at the disease site for longer before more serious damage occurs.”

Caroline Blakely, chief executive of Brain Research UK, said: “We’re excited to be funding this important work by Dr Al-Ahmady and collaborators, and hope that it will prove to be an important step towards improving outcomes for patients who have suffered a brain haemorrhage.

“We are only able to fund research like this thanks to the extraordinary efforts of our supporters, many of whom are raising funds in tribute to loved ones affected by brain conditions.”

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Research

‘Elite sleep’ genes could protect against neurodegenerative disease

The study contrasts with the belief that, for many people, lack of sleep can accelerate neurodegeneration

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People with ‘elite sleeper’ genes, which see them need only four to six hours of sleep a night, may also have some protection against neurodegenerative disease. 

A new study into Familial Natural Short Sleep (FNSS) – the ability to function fully on, and have a preference for, shorter amounts of sleep each night – shows this can run in families. 

To date, the team at UC San Francisco have identified five genes across the genome that play a role in enabling this efficient sleep, although the researchers believe there are many more FNSS genes to find.

And with the ability to thrive on limited levels of sleep can come psychological resilience and resistance to neurodegenerative conditions, which may play a role in fending off neurological disease. 

Dr Ying Hui Fu and Dr Louis Ptacek

“There’s a dogma in the field that everyone needs eight hours of sleep, but our work to date confirms that the amount of sleep people need differs based on genetics,” said neurologist Dr Louis Ptacek, one of the senior authors on the study. 

“Think of it as analogous to height; there’s no perfect amount of height, each person is different. We’ve shown that the case is similar for sleep.”

For over a decade, Ptacek and co-senior author, Dr Ying-Hui Fu, both members of the UCSF Weill Institute for Neurosciences, have been studying FNSS. 

This study tested Dr Fu’s hypothesis that elite sleep can be a shield against neurodegenerative disease. 

Her ideas contrast somewhat with current thinking that, for many people, lack of sleep can accelerate neurodegeneration. 

The difference, Dr Fu said, is that with FNSS, the brain accomplishes its sleep tasks in a shorter time. 

The team chose to look at mouse models of Alzheimer’s disease and bred mice that had both short-sleep gene and genes that predisposed them to Alzheimer’s. 

They found that their brains developed much less of the hallmark aggregates associated with dementia. 

To confirm their findings, they repeated the experiment using mice with a different short-sleep gene and another dementia gene and saw similar results.

Dr Fu and Dr Ptacek believe that similar investigations of other brain conditions would show the efficient-sleep genes conferring comparable protections. 

But in the general population, improving peoples’ sleep could delay progression of disease across a whole spectrum of conditions, they said.

Sleep problems are common in all diseases of the brain,” said Dr Fu. 

“This makes sense because sleep is a complex activity. 

“Many parts of your brain have to work together for you to fall asleep and to wake up. 

“When these parts of the brain are damaged, it makes it harder to sleep or get quality sleep.”

Understanding the biological underpinnings of sleep regulation could identify drugs that will help ward off problems with sleep disorders, the research team added. 

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