Researchers at the University of California San Diego have identified new mechanisms in neurons that cause Alzheimer’s disease.
In particular, they discovered that changes in the structure of chromatin, the tightly coiled form of DNA, trigger neurons to lose their specialised function and revert to an earlier cell state. This results in the loss of synaptic connections, an effect associated with memory loss and dementia.
The study was founded on the question: how do neurons in patients with Alzheimer’s disease differ from neurons in healthy individuals?
Shankar Subramaniam, professor of bioengineering at the UC San Diego Jacobs School of Engineering says: “It’s a fundamental question that would provide the framework and foundation for understanding Alzheimer’s disease at the cellular level, and thus pave the path for novel therapeutic approaches.”
Subramaniam worked with an interdisciplinary team of engineers and neuroscientists at UC San Diego to answer this question. They started by taking human induced pluripotent stem cells derived from patients with familial Alzheimer’s disease, which is a hereditary form of Alzheimer’s, and transformed them into neurons. They used next generation sequencing techniques to look at what genes are being expressed in these neurons and how gene expression is regulated, and then compared how they differ in neurons of healthy individuals.
They discovered that neurons derived from the patients de-differentiate to a precursor state.
“In other words, they cease to be neurons,” Subramaniam said. “This is the key defect observed across a diversity of patients with distinct mutations. The consequences to the brain are dramatic, with loss of synaptic connections leading to cognitive decline.”
The researchers observed other defects: neuronal genes are suppressed, so these cells no longer have any instructions telling them that they are neurons; they are in a precursor-like state, which means they can trigger cell growth and division–this is unusual because adult brains do not produce new neurons; and they have inflammation, which signals damage or stress.
The same defects were also observed in post-mortem human brain samples from patients with Alzheimer’s disease. “This was validating for our findings because we weren’t just seeing these mechanisms in the stem cells, but in actual brain samples as well,” Subramaniam said.
The researchers traced all of these mechanisms back to changes in the structure of chromatin. Parts of this structure consist of open regions, where genes are expressed or regulated, and other parts consist of closed regions, where gene expression is repressed. In the diseased neurons, some regions that used to be open are now closed, and vice versa. As a consequence, the neurons are not behaving as they should be, Subramaniam explained.
The team is now working on developing drugs to inhibit these mechanisms.
Two major neuro events postponed due to COVID-19
Two significant events in neuro practitioners’ calendars have been delayed until later in the year, as the effects of the COVID-19 pandemic continue to be felt.
The National Paediatric Brain Injury Conference, which was already revised from an in-person to online event, will now not go ahead as planned in February due to the continuing demands on frontline healthcare professionals as COVID-19 cases continue to rise and the country is plunged back into lockdown.
The event, organised by The Children’s Trust, is now earmarked for May 13, although that is subject to further developments in the pandemic.
The ‘Connections and Collaborations’ conference is set to attract an international audience and will hear from an array of speakers from around the world, many of whom are global leaders in the field of paediatric neuro care.
Explaining the postponement, Dalton Leong, chief executive of The Children’s Trust, says: “Over the years, a high number of attendees are from the NHS, including consultants, doctors, surgeons, nurses, and therapists.
“We know that many of these staff are being redeployed to support the Covid pandemic.
“To run a conference at this time, taking them away from delivering vital frontline services, does not seem a sensible option. We look forward to holding the conference later in the year when, hopefully, these pressures have reduced.”
As well as the conference, the Neuro Convention too has been postponed, moving from March until September to enable delegates to attend in person.
The event, held at the Birmingham NEC, typically attracts around 3,000 people from across the country, and organisers hope that by delaying the date, it will give the best chance of lockdown and social distancing measures being lifted to allow them to go ahead.
In addition to the event planned for September 15 and 16 – although that too may be subject to change – an additional digital version of Neuro Convention is set to go ahead in March, enabling neuro professionals to still receive the insight and analysis planned for the NEC event in an online format.
Neuro Convention is hailed as being Europe’s only specialist trade event for brain and spine experts, and boasts an array of internationally-respected speakers and leaders in their field.
“We have been in consultation with various Government departments and whilst the rollout of the vaccine has given the country much needed optimism, we have been advised that we will be unable to host the Neuro Convention event in the spring,” say event organisers Roar B2B.
“The safety of our visitors, customers, partners and staff is paramount. We are confident that moving the event to September will enable us to run the safe, successful event the industry demands.
“To support our exhibitors, partners and the wider industry we are delighted to announce an additional digital version of Neuro Convention. This will provide a digital meeting place, world-class speaking sessions and access to the latest products and services.”
Arm and hand function could be regained following spinal cord injury through new pioneering research
Treatment could be developed for arm and hand dysfunction in people living with spinal cord injury through a pioneering new research project.
A pilot study of new therapy for improving upper extremity function is now underway, following funding from BrainQ Technologies – an Israel-based startup which is working widely in precision medicine to reduce disability following neurodisorders – to the Kessler Foundation.
The study is titled ‘The safety and effectiveness of the use of a brain-computer interface-based electromagnetic field treatment in the management of patients with chronic spinal cord injury: A pilot study’ and is seen as a potentially significant breakthrough in researching possible treatment.
It will be led by Dr Ghaith Androwis, a research scientist in the Centre for Mobility and Rehabilitation Engineering Research at Kessler Foundation, and Dr Steven Kirshblum, senior medical officer and director of the Spinal Cord Injury Program for Kessler Institute for Rehabilitation, who received the grant to further their work in the field.
Thousands of new traumatic spinal cord injuries occur each year, with statistics showing around 17,500 of those are from the United States alone, and more than half of those people experience loss of motor function of the upper extremities which limits their independence and adversely affects their quality of life.
“To achieve the best outcomes after spinal cord injury, restoring arm and hand function must be a priority in rehabilitative care,” says Dr Kirshblum.
“This study is an important first step towards increasing the ability of individuals to function more independently at home, in their communities, and the workplace.”
During the study – which will be conducted in the US and Israel – researchers will test the safety and efficacy of noninvasive low frequency electromagnetic field stimulation delivered via the BQ System.
Individuals with spinal cord injury (duration 18-30 months) will participate in the 34-week study. Functional status will be measured at baseline and compared with status following the experimental treatment.
By quantifying gains in motor function, motor control and activities of daily living, this pilot study will provide preliminary information on the potential application of BrainQ’s therapy in rehabilitation programs for individuals with disability.
“We are very interested in testing the effectiveness of this novel and non-invasive approach in persons with spinal cord injury,” adds Dr. Androwis.
“Such interventions may improve participants’ performance of activities of daily living leading to gains in their overall quality of life. This particularly is important when an intervention can be provided simultaneously with conventional therapy.”
This multi-site study is being conducted at Kessler Foundation, The Miami Project to Cure Paralysis, Miami, and Sheba Medical Center, Israel.
‘My brain is slipping into my spine’
After years spent in pain and struggling for a diagnosis, Karl Johnston felt relief when he was confirmed as having a little-known condition where the brain effectively slips into the spine. Here, he shares his story.
“Some dads get to put their children on their shoulders, but I’ve never got to do that.”
That is just one of the day-to-day realities facing Karl Johnston, whose condition, Chiari Malformation Type 1, means his brain is effectively slipping into his spine.
For eight years, Karl had experienced a catalogue of symptoms, including intense and debilitating neck pain, light-headedness, fatigue and numbness in his arms, but without securing a diagnosis of his condition.
But now, the 35-year-old admits he feels some relief at the knowledge he has Chiari Malformation Type 1, as devastating as the diagnosis was to receive.
“A lot of people felt sorry for me when I finally got a diagnosis, but it was a relief because I’d been telling people that I was suffering for years and they hadn’t believed me,” says Karl, from Wallasey, on Merseyside.
“You start to question yourself about things. Just knowing takes a lot of the weight off you.
“Some days the pain is so much that it’s difficult to move around and all I want to do is lie down.”
The biggest difficulty emotionally, says Karl, is the impact it has on his ability to play with his daughter Seren.
“It’s devastating when she wants to play and I’m not up to it,” he says.
“Some dads get to put their children on their shoulders, but I’ve never got to do that.”
While Chiari Malformation Type 1 is most commonly diagnosed in adults, it is believed to often be present from birth.
Many people with the condition are asymptomatic, meaning it is only found if they have an MRI scan.
Karl had symptoms from when he was a teenager, but getting a diagnosis was difficult due to the lack of awareness around the condition.
He is now determined to help raise awareness of Chiari Malformation Type 1, in the hope that others may be able to secure a diagnosis quicker than his.
“There needs to be a way to make doctors and people in general more aware of these rarer conditions because otherwise people just fall through the cracks,” says Karl.
The dad-of-one has been supported by The Brain Charity, a national charity based in Liverpool that supports people with all forms of neurological conditions. Statistics show that 1 in 6 people in the UK is currently living with such a condition.
The charity recently told NR Times that demand for its services had soared by over 70 per cent since the start of lockdown in March, with predictions that the numbers of people needing support with issues including mental health, Long Covid and employment rights would grow further still.
Having turned to the charity last year, Karl is now getting the practical and emotional support he needs to get on with his life.
“The Brain Charity helped me get a better understanding of what was going on with my condition,” he says.
“It has felt like so many people haven’t taken me seriously but The Brain Charity has.
“They didn’t pity me but tried to understand what I was going through.”
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