Connect with us

Research

New drug could treat dyskinesia in Parkinson’s disease

Published

on

Early trial results give hope for a new potential dyskinesia treatment for people with Parkinson’s disease.

A new clinical trial, carried out by Neurolixis and made possible by co-funding from the Parkinson’s Virtual Biotech and The Michael J Fox Foundation for Parkinson’s Research (MJFF), shows that the drug NLX-112 is safe and effective in reducing dyskinesia in patients with Parkinson’s disease.

Over the last five years, the Parkinson’s Virtual Biotech has provided US based biotech company, Neurolixis, with a total of £1.57 million in funding to support the progress of NLX-112 through preclinical research and clinical trials. 

Neurolixis has been researching the effect of the drug NLX-112 on dyskinesia, a common side effect experienced by people with Parkinson’s who have been taking levodopa-based medications for several years. 

It causes involuntary movements that can affect various parts of the body, making everyday tasks impossible. The main medication available to manage dyskinesia is amantadine, which can have side effects and does not work for everyone.

NLX-112 works by targeting serotonin cells inside the brain which are believed to contribute to the development of dyskinesia, by releasing dopamine in an erratic manner. It aims to reduce dyskinesia by decreasing the amount of dopamine the cells release.

This latest phase 2a study firstly looked at how safe and well tolerated NLX-112 was in people with Parkinson’s and also how well NLX-112 improved their dyskinesia symptoms. Of the 22 participants with levodopa-induced dyskinesia who completed the treatment process, 15 participants received NLX-112 and seven participants received a placebo.

Participants either received NLX-112 or placebo in increasing doses during the initial four weeks, to minimise the potential side effects. After two weeks at the maximum dose, they decreased the dosage over two weeks.

The results achieved the first objective to suggest that NLX-112 was safe and well tolerated in people with Parkinson’s. 

The second aim of the study was to show that NLX- 112 was effective in treating dyskinesia. The results suggest participants who received NLX-112 showed significant reduction in their scores for dyskinesia, whereas those who received the placebo did not show significant reduction in their scores.

The side effects of participants who received NLX-112 were mild, confirming previous observations on the compound. Full analysis of efficacy measures is underway and will be disclosed in further announcements.

Professor Per Svenningsson, principal clinical investigator, said: “We are excited about the positive results of this proof-of-concept study. The findings indicate that NLX-112 can be safely administered to people with PD [Parkinson’s disease] and alleviates their troublesome LID. If these findings are confirmed in larger clinical trials, NLX-112 could become a promising new treatment option for this indication.”

The Parkinson’s Virtual Biotech, led by charity Parkinson’s UK in partnership with the Parkinson’s Foundation, fast-tracks the projects with the greatest scientific potential to transform the lives of people with Parkinson’s, focusing on treatments that will meet the most pressing needs identified by the Parkinson’s community.

Dr Arthur Roach, Director of Research at Parkinson’s UK, said: “We’re incredibly proud and excited by these early results from Neurolixis. They were one of the first companies that the Parkinson’s Virtual Biotech invested in, in partnership with The Michael J Fox Foundation, so to see it making positive progress just reiterates why this brave and innovative approach is right for the Parkinson’s community. It really is bringing us closer to new treatments that address the symptoms that the Parkinson’s community have told us are the most urgent and LID is one of those.

“The Parkinson’s Virtual Biotech is a global partnership between Parkinson’s UK, the largest charitable funder of Parkinson’s research in Europe, and the Parkinson’s Foundation, but it is entirely driven by the Parkinson’s community. Further studies will be necessary for regulatory approval and routine clinical use of NLX-112. But now people with Parkinson’s can have hope that a much needed new treatment for LID may be coming to them soon, and know that their support of the Parkinson’s Virtual Biotech has made this possible.”

Dr. Adrian Newman-Tancredi, CEO of Neurolixis, added: “PD is the fastest growing neurodegenerative disease and these results suggest that NLX-112 could help mitigate the medical and societal burden caused by this disease. We are grateful to the Parkinson’s Virtual Biotech and the Michael J Fox Foundation for financially supporting investigation of NLX-112 from preclinical studies through to this clinical trial, and their recognised expertise in the PD field provides a strong validation for the program. These positive findings further support the development of NLX-112 as a potential treatment for LID and other movement disorders with large market potential.”

 

Research

How older people explore new spaces could suggest dementia

Published

on

Results from a new study have shown an analogous shift in exploration behaviour in middle age for the first time in humans.

Spatial navigation – the ability to select and follow a route from one place to another – is a skill we use every day. Depending on practice, general cognitive ability, and childhood environment, some people are naturally better at this than others.

However, research has also shown that people’s skill in spatial navigation tends to decrease with increasing age.

This decline in navigation skill has been generally attributed to worsening spatial memory, due to changes in brain structure and function that naturally occur with age. But what if it isn’t just due to our spatial memory declining, but also to changes in how we explore a novel environment? Such a shift has been observed in aging animals, ranging from insects to rodents and fish.

An exploratory study

Results from this new study, published in Frontiers in Aging Neuroscience, could have clinical applications.

First author Dr Vaisakh Puthusseryppady, a postdoctoral researcher at the University of California at Irvine, stated: “Compared to younger individuals, middle-aged people exhibit overall less exploration when learning a novel maze environment, and seem to be prioritising learning specific important locations in the maze as opposed to the overall maze layout.”

Puthusseryppady and colleagues recruited 87 middle-aged (on average 50 years old) and 50 young (on average 19 years old) women and men as volunteers. None had a history of neurologic disease including dementia, or psychiatric illness.

The researchers tested how well the volunteers explored and learned to navigate a maze in virtual reality. The maze was composed of crossroads and corridors, separated by hedges. Distinctive objects were scattered around it at strategic locations as landmarks. In the first ‘exploration phase’, the volunteers were instructed to freely explore the maze and learn the locations of the objects.

In each of the 24 trials in the second ‘wayfinding phase’, the volunteers had to apply what they had learnt, navigating between two randomly chosen objects within 45 seconds.

As expected, young people on average had a greater success rate in finding their way. But importantly, further statistical analyses showed that this difference in success rate was partially driven by observed qualitative changes in how young vs middle-aged participants learned about the maze.

“Compared to younger individuals, middle-aged individuals explored the maze environment less, as they travelled less distance, paused for longer periods of time at decision points, and visited more objects than young individuals,” said Dr Mary Hegarty, a professor at the Department of Psychological and Brain Sciences of the University of California at Santa Barbara, and a joint corresponding author.

These differences were so notable, the authors were able to predict using artificial intelligence whether a participant was middle-aged or young.

Pointing the way for applications

Reduced exploration in middle-aged people may be due to age-related changes in the brain’s navigation network, for example the medial temporal and parietal lobes.

The authors speculated that these findings could inform training interventions that can help middle-aged adults to improve their navigation abilities and preserve cognitive ability.

Co-author Daniela Cossio, a PhD student at the University of California at Irvine, explained: “If we were to train middle-aged people to explore novel environments better – with a focus on traveling greater distances, visiting paths that connect the environment, in a more spread-out manner – this might lead to improvements in their spatial memory, helping to slow down their decline in cognitive ability.”

Dr Elizabeth Chrastil, one of the corresponding authors, and an associate professor at the same institute, looked ahead: “We are currently investigating whether these kinds of changes in exploration behaviour can be identified in people at risk of Alzheimer’s Disease, as well as in those who actually have Alzheimer’s.

“We anticipate that altered exploration behaviour could ultimately become a novel clinical marker for early cognitive decline related to Alzheimer’s.”

Continue Reading

Research

Lung cancer screening prolongs lives in real-world study

Published

on

Among US veterans diagnosed with lung cancer through the Veterans Health Administration healthcare system, those who underwent screening before diagnosis were more likely to be diagnosed with earlier stage disease and had a higher cure rate than those who had not been screened.

Lung cancer is the leading cause of cancer deaths worldwide, and most patients are diagnosed at an advanced stage.

Early detection through screening could save lives, and current recommendations state that adults 50–80 years old with at least a 20-pack-year smoking history who currently smoke or have quit within the past 15 years should undergo annual imaging tests for lung cancer.

Such screening has been shown to be beneficial in clinical trials, but there are limited data on the real-world effectiveness of lung cancer screening. To investigate, researchers assessed the impact of screening among patients in the Veterans Health Administration healthcare system diagnosed with lung cancer from 2011–2018.

Among 57,919 individuals diagnosed with lung cancer, 2,167 (3.9%) underwent screening before diagnosis. Patients who underwent screening had higher rates of early (stage I) diagnoses compared with those who had no screening (52% versus 27%), lower rates of death from any cause (49.8% versus 72.1%), and death from cancer (41.0% versus 70.3%) over 5 years.

“It is incredible to witness how dedicated national efforts to increase lung cancer screening from the Lung Precision Oncology Program can lead to substantial improvements in lung cancer outcomes,” said co–corresponding author Michael Green, MD, PhD, of the University of Michigan and the Veterans Affairs Ann Arbor Healthcare System.

The findings come from an observational study published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Continue Reading

Research

Pioneering therapy approach to combat age-related vision loss

Published

on

Cirrus Therapeutics, the University of Bristol, and London’s Global University Institute of Ophthalmology have discovered a revolutionary treatment for age-related macular degeneration (AMD), the leading cause of vision loss among older adults.

Featured on the cover of the journal Science Translational Medicine, this breakthrough research reveals that boosting a specific protein, IRAK-M, in retinal cells could offer a new and highly effective therapy for AMD.

AMD can severely impact a person’s vision. Patients suffering from AMD often start with blurred vision or seeing a black dot in their central vision, which can ultimately expand to the point where there is no useful central vision. Currently, AMD affects approximately 200 million people worldwide, a number projected to rise to 288 million by 2040 with graying populations.

The exact cause of AMD is complex and thought to involve a combination of aging, environmental, and lifestyle factors.

The team found that augmenting IRAK-M levels in retinal cells can significantly protect against retinal degeneration.

“This discovery represents the first pathway-agnostic approach toward AMD, offering a comprehensive treatment option for the millions of people who suffer from this debilitating condition,” said Dr. Andrew Dick, Head of the Academic Unit of Ophthalmology at the University of Bristol, Director of the UCL Institute of Ophthalmology, and co-founder and Chief Scientific Advisor of Cirrus Therapeutics.

Dr. Jian Liu, the first author and senior research scientist at the Academic Unit of Ophthalmology of the University of Bristol, added: “Since age stands as a primary risk factor for AMD, the gradual decrease of IRAK- M levels with age, which further declines in AMD, is a key way to identify the potential markers of early AMD progression and ultimately a new way of treatment.”

This discovery will build and improve upon current treatments for AMD, which are targeting single pathophysiology pathways. “Our novel approach not only addresses the multiple pathways involved in treating AMD but also offers the most compelling and evidence-based strategy available today,” said Cirrus Therapeutics co-founder and Chief Executive Officer Dr. Ying Kai Chan.

Cirrus Therapeutics recently spun out of the University of Bristol to develop therapies related to this discovery.

The research for this paper was funded by the Rosetrees Trust, Stoneygate Trust, Underwood Trust, Macular Society, Sight Research UK, Moran Eye Center at the University of Utah, Sharon Eccles Steele Center for Translation, and supported by the National Institute for Health and Care Research (NIHR) BRC Moorfields and UCL-Institute of Ophthalmology.

Continue Reading

Trending