New clues are being discovered around the onset of Huntington’s disease, which have been hailed as a “powerful new tool” to test new therapies.
Through the development of a new mouse model of the disease, which recapitulates more Huntington’s disease-like characteristics than earlier models, researchers are able to discover more about how genetic mutations dictate the disease onset.
Huntington’s is a familial neurodegenerative disorder in which a child of parents with the disease has a 50-50 chance of inheriting the causative mutated gene, named huntingtin.
“Since Huntington’s disease is caused by a single gene mutation, conceivably it should be easier for therapeutic intervention,” said Dr X. William Yang, professor of psychiatry and biobehavioral sciences and the Terry Semel Chair in Alzheimer’s Disease Research and Treatment at the David Geffen School of Medicine at UCLA.
“However, even though this mutation was found about 30 years ago and scientists around the world fight very hard to find disease-modifying treatment, so far, all the efforts are yet to be successful, especially with the halting of last year’s promising clinical trial to lower mutant huntingtin expression that was a setback to the HD community.”
Huntington’s leads to a variety of symptoms, such as personality changes, impaired judgment, unsteady gait and involuntary movements, and speech and swallowing impairment. Although it usually begins between ages 30 and 50, an earlier onset – under age 20 – or later onset, after age 70, can occur.
This study by the Yang Lab was designed to answer a genetic mystery in Huntington’s disease.
Previous studies in the field had focused on the toxic protein products encoded by the CAG repeats, a string of amino acid residues (glutamine) that are toxic to neurons.
However, recent human genetic studies with thousands of Huntington’s patients revealed an unexpected finding, in that patients with CAA interruptions (CAA also encodes glutamine) in the CAG repeats have a later onset of the disease compared to patients without such interruptions but with the same glutamine repeat.
“In this study, we developed the first human genomic transgenic mouse model of Huntington’s disease with long – about 120 – uninterrupted CAG repeats and compared the new model to our previous HD model with frequent CAA interruptions,” said Dr Yang.
“Together, they showed that the long CAG repeat is selectively toxic to the striatum, the brain region that controls movement and cognition and is the most affected in Huntington’s disease.”
The new mouse model has a subset of Huntington’s disease-like behavioural deficits, such as motor deficits and sleep disorders, and other characteristics that are largely absent in previous mouse models carrying the human huntingtin gene, such as pathological changes in non-neuronal cells and broad dysregulation of gene expression in the HD-vulnerable brain region.
“Our new model is unique from a therapeutic perspective as it has the entire human huntingtin gene, including several DNA variants present in the patients, and it has a long and pure CAG repeat,” said first author Dr Xiaofeng Gu, a project scientist in the Center for Neurobehavioral Genetics at the Semel Institute who was primarily responsible for engineering and characterising the mouse model.
The new model developed in the Semel Institute at UCLA can be used to test candidate therapies to lower the human huntingtin and those targeting the toxicities originated from the pure CAG repeats in huntingtin, said Dr Yang, adding that it also can be used to test combinatory therapies against both types of targets.
Currently, the new model has already been used by two pharmaceutical companies and several academic labs to test their therapeutic interventions.
Royal Rehab opens Australia’s largest technology centre
The centre caters for people living with disabilities across the country
Royal Rehab, Australia’s not-for-profit provider of rehabilitation and disability support services, opens the country’s largest technology centre, providing Australians with access to a comprehensive range of technology.
Royal Rehab’s Advanced Technology Centre is a purpose-built hub designed to improve the rehabilitation outcomes of people impacted by life changing illnesses or injuries. The centre also caters for people living with disabilities, by providing expert support and access to technologies that aim to improve function, strength and wellbeing and is the largest of its kind in Australia.
The C-Mill VR+ technology combines a treadmill with body weight supports and virtual and augmented reality to improve balance, gait, and gait adaptability in a controlled environment. The device provides a safe and comfortable training environment that mimics the challenges of real-life, helping users to navigate situations like walking in crowded areas and avoiding obstacles.
The centre is also home to a Zero G Gait and Balance System, which has the longest walking track in the country. This device is a robotic body weight support that is designed to assist those affected by spinal cord injuries, brain injuries, neurological conditions and degenerative conditions to walk.
It allows falls prevention training to minimise patient risk, so they can focus on regaining their confidence in walking, balancing, climbing stairs and manoeuvring from sitting to standing positions.
Matt Mackay, CEO of Royal Rehab, believes technology can play a significant role in unlocking better patient outcomes and that the opening of Royal Rehab’s Advanced Technology Centre will make innovative technology more accessible.
“We know that the use of technology in combination with traditional therapies has the potential to drive better outcomes,” he says. “This will revolutionise the rehabilitation pathway for many patients, which in turn can lead to dramatic changes in a person’s quality of life.
“Our Advanced Technology Centre provides Australians with the opportunity to access potentially life-changing devices, many of which have never been accessible in Australia until now. We are delighted to be able to provide patients access to emerging advanced technologies that has the potential to accelerate rehabilitation progress and help people to improve their function, mobility and strength, the CEO adds.
“We want to provide people living with a long-term disability access to these technologies, so they too can benefit from improved strength and fitness, and maintain or even improve their functional independence.”
Jason Redhead, senior physiotherapist and technology lead at Royal Rehab, says that the centre offers Australian patients exclusive access to advanced technologies that will provide greater opportunities to achieve their rehabilitation goals, adding: “We have seen that advanced technology is starting to play a leading role in rehabilitation programs in many other countries.
“We want to ensure Australians too can access the best technology, like robotic exoskeletons, body weight support systems, upper limb robotics and virtual reality technologies. This means we will see more patients achieve more in their rehabilitation goals.”
The centre operates under the Royal Rehab LifeWorks banner, which provides Australians with access to a multidisciplinary team of allied health clinicians who work together with patients and clients on their individualised goals to develop integrated therapy and wellness programmes.
Royal Rehab’s Advanced Technology Centre is located at their Ryde location and will open its doors on July 1. Access to the centre is covered under a range of funding options, including NDIS, iCare, and self-funding.
Neuro Convention returns next week
The event brings together neuro-rehab professionals and leading organisations from across the UK
Neuro-rehab professionals and organisations will be attending one of the key dates in the sector calendar next week – Neuro Convention 2022.
The event showcases the latest technology and innovations in the neurological sector, with the goal of improving patient outcomes.
Neuro Convention, held on Wednesday and Thursday at the NEC Birmingham, will focus on four key areas – rehabilitation, mental health, diagnostics and brain and spinal injury.
The free event includes a programme of more than 50 free CPD-accredited seminars, hosted by leading experts from across neuro-rehab, as well as interactive workshops hosted by the specialist neuro-rehab team at the University of Plymouth.
Technology will also be showcased, with a programme of live demonstrations, to show how the latest innovation can benefit people’s lives.
More than 50 exhibitors will also be in attendance, including the team from NR Times, who can be found on stand N-G3.
Neuro Convention will be co-located with Naidex and UK Care Week within the NEC, highlighting the shared dedication of all three events to improve mobility and the technology introduced to support independent living.
Deborah Johnson, editor of NR Times, who will be attending Neuro Convention, said: “Neuro Convention is known as being one of the must-attend events in the neuro-rehab calendar, and 2022 looks to be another excellent event, with a packed programme of speakers and workshops and an array of leading exhibitors.
“It’s absolutely fantastic that the opportunities for the neuro-rehab sector to come together again in person are returning, and I’m personally looking forward to meeting as many people as possible – those who are new to NR Times, others who are old friends, and those who to date we have only met via Zoom!”
Tickets are free and to register, visit here.
Dates & Times
Wednesday 6th July 2022 | 09:30 – 16:30
Thursday 7th July 2022 | 09:30 – 16:00
National Exhibition Centre (NEC)
B40 1NT, UK
Social links #NeuroCon
Role of sleep in memory and learning uncovered
Research findings could aid development of assistive tools for people with neurological injury or disease
New research into sleep may help explain how memories are formed and how learning is consolidated, and could aid the development of assistive tools for people affected by neurological injury or disease.
Scientists previously studying laboratory animals discovered a phenomenon known as ‘replay’ that occurs during sleep – a strategy the brain uses to remember new information.
Scientists believe that this replay of neuronal firing during sleep is how the brain practices newly-learned information, which allows a memory to be consolidated, and converted from a short-term memory to a long-term one.
However, replay has only been convincingly shown in lab animals.
Now, a new study has investigated whether replay occurs in the human motor cortex — the brain region that governs movement — focusing on a 36-year-old man with tetraplegia who cannot move his upper and lower limbs due to a spinal cord injury.
The man, identified in the study as T11, is a participant in a clinical trial of a brain-computer interface device that allows him to use a computer cursor and keyboard on a screen.
The investigational device being developed by the BrainGate consortium, a collaborative effort involving clinicians, neuroscientists and engineers at several institutions with the goal of creating technologies to restore communication, mobility, and independence for people with neurologic disease, injury, or limb loss.
In the study, T11 was asked to perform a memory task similar to the electronic game Simon, in which a player observes a pattern of flashing coloured lights, then has to recall and reproduce that sequence.
He controlled the cursor on the computer screen simply by thinking about the movement of his own hand. Sensors implanted in T11’s motor cortex measured patterns of neuronal firing, which reflected his intended hand movement, allowing him to move the cursor around on the screen and click it at his desired locations.
These brain signals were recorded and wirelessly transmitted to a computer.
That night, while T11 slept at home, activity in his motor cortex was recorded and wirelessly transmitted to a computer.
“What we found was pretty incredible,” said Dr Daniel Rubin, lead author and a neurologist at the MGH Center for Neurotechnology and Neurorecovery.
“He was basically playing the game overnight in his sleep.
“This is the most direct evidence of replay from motor cortex that’s ever been seen during sleep in humans.”
Most of the replay detected in the study occurred during slow-wave sleep, a phase of deep slumber.
Interestingly, replay was much less likely to be detected while T11 was in REM sleep, the phase most commonly associated with dreaming.
The researchers see this work as a foundation for learning more about replay and its role in learning and memory in humans.
“Our hope is that we can leverage this information to help build better brain-computer interfaces and come up with paradigms that help people learn more quickly and efficiently in order to regain control after an injury,” said neurologist Dr Sydney S. Cash, co-director of the Center for Neurotechnology and Neurorecovery at MGH.
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