Author: Rachael Hansford

Trofinetide for Rett Syndrome – new drug submission in Canada 

Posted on April 23, 2024 by - Neurodevelopmental disorders

23 April 2024: Acadia Pharmaceuticals Inc has announced that Health Canada has accepted its New Drug Submission (NDS) for trofinetide for the treatment of Rett syndrome, a rare neurodevelopmental disorder. Health Canada has granted Priority Review for Acadia’s submission.

“Rett syndrome is a profoundly debilitating and complex neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms,” said Pamela di Cenzo, Vice President, General Manager, Rare Disease, Canada at Acadia. “If granted marketing authorisation, trofinetide will be the first option available to treat Rett syndrome in Canada.”

Health Canada grants Priority Review for drug submissions intended for the treatment, prevention, or diagnosis of serious, life-threatening, or severely debilitating illnesses or conditions for which there is substantial evidence of clinical effectiveness that the drug addresses an unmet medical need or provides a benefit/risk profile that is improved over existing therapies.

“O.R.S.A. is pleased that Health Canada has granted Priority Review for this promising treatment which, if approved, would be a significant step forward in addressing the unmet medical needs of Canadians living with Rett syndrome,” said Sabrina Millson, President of the Ontario Rett Syndrome Association (O.R.S.A.). “Our community of patients, caregivers and supporters are excited at the prospect of having a treatment option for Rett syndrome.”

The Health Canada filing is supported by results from the positive pivotal Phase 3 LAVENDER™ study evaluating the efficacy and safety of trofinetide versus placebo in 187 girls and young women with Rett syndrome. The co-primary endpoints were change from baseline in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score, a caregiver assessment, and Clinical Global Impression–Improvement (CGI-I) scale score, clinician perspective, at week 12; both were statistically significant. The key secondary endpoint measuring improvements in communication was also statistically significant. Trofinetide has been approved for the treatment of Rett syndrome in adult and paediatric patients two years of age and older in the United States, and it is not currently authorised for sale in Canada for the treatment of Rett syndrome.

About Rett Syndrome

Rett syndrome is a rare genetic neurodevelopmental disorder that occurs primarily in females following a near normal development in the first two years of life.1,2 It is caused by mutations on the X chromosome on a gene called MECP2.3 Rett syndrome is a complex and multisystem disorder that causes profound impairment to central nervous system (CNS) function, including loss of communication skills, purposeful hand use, gait abnormalities, and stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms.2

Rett syndrome occurs worldwide in approximately one of every 10,000 to 15,000 female births.4 In Canada, prevalence of Rett syndrome is estimated to be 600 to 900 patients.5 Children with Rett syndrome experience a period of developmental regression between 18-30 months of age, which is typically followed by a plateau period lasting years to decades.1-3 Rett syndrome is diagnosed based on clinical evaluation, typically by about three years of age.2,6

References

1 Fu et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open. 2020;4:1-14.
2 Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68(6):944-950.
3 Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999; 23(2):185-188.
4 May DM, Neul JL, Satija A, et al. Real-world clinical management of individuals with Rett syndrome: a physician survey. J of Med Econ. 26(1), 1570–1580.
5 Acadia Pharmaceuticals Inc. Data on File. Canada prevalence of Rett syndrome. February 2024.
6 Tarquinio DC, Hou W, Neul JL, et al. Age of Diagnosis in Rett Syndrome: Patterns of Recognition Among Diagnosticians and Risk Factors for Late Diagnosis. Pediatric Neurology. 2015;52:585-591.

Clinical trial for ALS patients

Posted on April 10, 2024 by - Amyotrophic Lateral Sclerosis (ALS)

  • Phase II trial will assess efficacy and tolerability of NX210c in Amyotrophic Lateral Sclerosis (ALS) patients
  • 80 patients due to be enrolled with first results expected in early 2026
  • NX210c drug candidate allows for promising approach to repairing Blood Brain Barrier (BBB) which is impaired in neurodegenerative diseases such as ALS

10 April 2024: Axoltis Pharma, a French biopharmaceutical company dedicated to developing therapeutic solutions for neurodegenerative diseases, today announced the authorisation from ANSM, the French agency for the safety of health products, to launch the SEALS study. This phase II clinical trial of drug candidate NX210c in patients with Amyotrophic Lateral Sclerosis (ALS) is the first to target the integrity of the Blood Brain Barrier (BBB).

ALS is a fatal neurodegenerative disease affecting 50,000 individuals in Europe at any time, resulting in 10,000 deaths each year. It predominantly affects motor neurons in both the brain and spinal cord. This leads to muscular weakness and paralysis, with most patients succumbing to respiratory failure within, on average, two to five years. Today, there is no cure for ALS and the only approved drug in the EU for the disease is Riluzole, prolonging survival for a median of just two months. Therefore, ALS remains a progressive and fatal neurologic disease of high unmet need.

It has been shown that the BBB, which protects against undesirable blood components crossing into the brain, is impaired in several neurodegenerative conditions, such as ALS, and may even be disease-driving. Axoltis’ NX210c is an innovative therapeutic agent with the ability to help the BBB recover its integrity, in addition to offering neuroprotection and promoting neurotransmission. NX210c is a cyclic peptide of 12 amino acids designed from the most conserved sequence of the type 1 thrombospondin repeats of the SCO-spondin.

The therapeutic approach of recovering BBB integrity in ALS patients is very promising; here at Axoltis we are proud to have a marked head start in the clinic with NX210c. The use of advanced analytical methods will offer a fresh approach to tackling ALS and contribute to the understanding of neurodegenerative diseases overall.

Dr Annette Janus, neurologist and chief medical officer at Axoltis

SEALS is a double-blind, randomised, placebo-controlled, multicentric phase II study that will assess the efficacy, safety, tolerability and pharmacokinetics of NX210c treatment in ALS patients. Its primary objective is to assess the effect of NX210c via two markers: Neurofilament Light chain (NfL) concentration in the blood, as a diagnostic and prognostic of axonal damage relevant to ALS, as well as the ratio of albumin concentration between CerebroSpinal Fluid (CSF) and blood, which has long been a reliable biomarker of BBB integrity. The study will also evaluate the effect of NX210c on functional outcomes and select secondary biomarkers. The first results are expected by early 2026.
 
Axoltis aims to enroll a total of 80 ALS patients in a trial planned in France with at least 15 investigating sites. Patients will receive a 10-minute IV infusion of the study drug at doses of 5 mg/kg or 10 mg/kg NX210c, or placebo, three times a week over four weeks. Patients will be able to continue the standard of care they have been receiving prior to receiving the study drug and will be followed-up for three months after the end of the treatment. Axoltis will receive operational support from the ACT4ALS/MND network.
 
Dr Emilien Bernard, head of the Lyon ALS center at the Hôpital Neurologique et Neurochirurgical Pierre-Wertheimer, Hospices Civils de Lyon, who will act as investigation coordinator, said: “This approach is very interesting and promising. It could certainly play a role on the path to finding a therapeutic solution to this terrible disease.”
 
“Receiving the authorisation to start this phase II clinical trial is a major achievement for the company, especially in ALS, where the unmet medical need is so important. In addition, there is a broad range of applications in CNS diseases where the BBB recovery could change their course, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and more,” added Dr. Yann Godfrin, chief executive officer at Axoltis Pharma.
 
In another pioneering step, the clinical trial will also incorporate statistical enrichment of the placebo group by adding virtual, in silico patients, based on computational methods of historical control data. This modelling, performed in collaboration with InSilicoTrials (Italy) will create predictions of disease progression in virtual subjects based on actual enrolled patients’ baseline characteristics.
 
Part of the study is supported by the Region Auvergne-Rhône-Alpes and the French Government through i-Demo Régionalisé, a France 2030 grant.
 
About NX210c
A large glycoprotein (SCO-spondin) produced by the subcommissural organ (SCO) plays crucial roles in neurogenesis and axonal guidance during embryogenesis. Only remnants of the SCO subsist in adults, thereby halting the production of SCO-spondin, which may account for a lack of regeneration and recovery in patients with neurological disorders. In this context, Axoltis is developing NX210c, a cyclic peptide of 12 amino acids designed from the most conserved sequence of the type 1 thrombospondin repeats of the SCO-spondin, as an innovative therapy for neurodegenerative diseases and traumas. NX210c is protected by seven patents fully owned by Axoltis Pharma, including one for composition of matter. In 2022, the FDA granted Orphan Drug Designation for NX210c in ALS. In 2023, the safety data collected in a phase Ib multiple ascending dose study showed NX210c to be well-tolerated and without safety concerns.
For more details: https://www.axoltis.com/our-product/properties/
 
About Axoltis Pharma
Axoltis Pharma, a French biopharma company, develops innovative drugs for neurodegenerative and neurotraumatic diseases with a high unmet medical need. Headquartered in Clermont-Ferrand, with offices in Lyon, (France), Axoltis has established several partnerships with internationally recognised academic and private labs to develop its lead product, NX210c. The team is highly experienced in drug development, especially for neurological applications.
http://www.axoltis.com

Blood tests for diagnosing dementia a step closer for UK

Posted on April 4, 2024 by - Alzheimer's Disease, Dementia

Two research teams will carry out UK-wide trials to identify accurate and quick blood tests that can diagnose dementia, in a bid to improve the UK’s diagnosis rate.  

Research teams at University College London, and Dementias Platform UK based at the University of Oxford, will capitalise on recent breakthroughs in potential dementia blood tests, and generate the evidence needed for them to be validated for use in the NHS within the next 5 years.  

The teams make up the Blood Biomarker Challenge – a multi-million pound award given by Alzheimer’s Society, Alzheimer’s Research UK and the National Institute for Health and Care Research and Gates Ventures including £5m raised by players of People’s Postcode Lottery. The project aims to revolutionise dementia diagnosis.  

Both teams will recruit participants from sites spread across the country, to ensure their findings are applicable to the whole of the UK’s diverse population.  

Timely and accurate diagnosis of the diseases that cause dementia, such as Alzheimer’s disease, is crucial as it means people can access vital care and support and take part in medical research. This will be even more imperative if new treatments are approved for use in the NHS, as these work best for people in the earliest stage of their disease.  

Currently, people are usually diagnosed using memory tests and brain scans. These are less accurate than ‘gold standard’ tests like PET scans or lumbar punctures, which can confirm what type of dementia they have. However, only 2% of people can access these specialist tests.  

Blood tests for diagnosing dementia

In recent years, a number of different blood tests for diagnosing dementia have shown very promising results in research settings. But they have yet to be tested widely in clinical settings in the UK.  

The READ-OUT* team will be led by Dr Vanessa Raymont, Professor James Rowe and Dr Ivan Koychev with Dementias Platform UK researchers from the Universities of Oxford and Cambridge. They will test multiple existing and novel blood tests, looking at a range of types of dementia, including Alzheimer’s disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. The researchers will also look at whether the blood tests can help detect these diseases at various stages.  

Led by Professor Jonathan Schott and Dr Ashvini Keshavan at University College London, the ADAPT team** will focus on the most promising biomarker for Alzheimer’s disease, called p-tau217. This reflects levels of two hallmark proteins found inside the brain in Alzheimer’s disease – amyloid and tau. The researchers will carry out a clinical trial to see whether measuring p-tau217 in the blood increases the rate of diagnosis for Alzheimer’s disease both in people with early dementia, but also in those with mild, progressive problems with memory.  

These complementary research approaches will maximise the chances of providing the evidence needed to prove that blood tests are ready for use in the NHS. They will pave the way for them to be made available to all who might benefit within the next 5 years.  

With more than half of all local authority districts in England failing to meet the government’s target dementia diagnosis rate of 66.7%, and with new drugs on the horizon which appear to slow early Alzheimer’s disease, experts from both charities and the research teams agree that change is needed.  

Professor Jonathan Schott, Alzheimer’s Research UK Chief Medical Officer and Professor of Neurology, UCL Queen Square Institute of Neurology, said: “An early, accurate diagnosis of Alzheimer’s disease is already important, allowing people to access to appropriate care and medications. If, as we hope, new treatments that can slow down Alzheimer’s disease become available soon, then this will be vital. This would pave the way for fair and equitable access to new and potentially life-changing treatments to all who might benefit.”  

Dr Vanessa Raymont, Associate Director, Dementias Platform UK and Senior Clinical Researcher, University of Oxford, said: “Since I first stepped into a memory clinic 30 years ago there has thankfully been a shift in the way society thinks about dementia. There was previously a feeling that this was just another part of aging, but now we’re seeing that people want to know more about their condition and they want a diagnosis as it helps them access the support they need. Both my parents lived with dementia so I know firsthand the devastation this disease causes, and how a timely and accurate diagnosis can benefit people and their families.”  

Fiona Carragher, Director of Research and Influencing at Alzheimer’s Society, said: “Dementia is the UK’s biggest killer, yet a third of people living with dementia don’t have a diagnosis, which means they’re not able to access care and support. An early and accurate diagnosis is also going to be vital in the future for identifying people who are most likely to benefit from new treatments, which are now within reach.  

At the moment only 2% of people with dementia can access the specialised tests needed to demonstrate eligibility for new treatments, leading to unnecessary delays, worry and uncertainty. Blood tests are part of the answer to this problem – they’re quick, easy to administer and cheaper than current, more complex tests. I’ve spent decades working in research and the NHS and, after years of slow progress, it feels like we’re on the cusp of a new chapter on how we treat dementia in this country. 

Fiona Carragher, Director of Research and Influencing at Alzheimer’s Society

Dr Sheona Scales, Director of Research at Alzheimer’s Research UK, said: “We’ve seen the enormous potential that blood tests are showing for improving the diagnostic process for people and their loved ones in other disease areas. Now we need to see this same step-change in dementia, which is the greatest health challenge facing the UK.   “It’s fantastic that through collaborating with the leading experts in the dementia community, we can look to bring cutting-edge blood tests for diagnosing dementia within the NHS. And this will be key to widening access to groundbreaking new treatments that are on the horizon.”  

For more information about the Blood Biomarker Challenge and how to take part, please visit: www.dementiasplatform.uk

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* The READ-OUT team (REAl World Dementia OUTcomes) for the first 3 years will run a fact finding study that will take blood tests in around 20 Dementias Platform UK sites across the UK, involving 3000 people from diverse populations. In the final 2 years, they will run a clinical trial with 880 people to explore how having a blood test for dementia affects diagnosis and quality of life, patients and carers, impact on care and how the results should be communicated to patients.

**The ADAPT team (Alzheimer’s disease Diagnosis And Plasma pTau217) will establish a ptau217 assay for use in the NHS before conducting a clinical trial with 1100 participants. Half will receive their test results after 3 months and half after 12 months, in order to understand whether the test makes a difference to the care their receive, the cost of their care and their quality of life.

Position of stroke patient’s head before surgery may improve neurological function

Posted on February 26, 2024 by - Stroke

Research Highlights: from American Stroke Association International Stroke Conference, February 2024

  • Hospital beds for stroke patients are typically elevated at the head, however, a flat head position before surgical removal of a blood clot in the brain (thrombectomy) may lead to better outcomes.
  • Results from a multicentre trial in the U.S. found significant improvements in clinical stability and neurological function for patients with 0-degree head positioning compared to patients with head positioning at a 30-degree angle, suggesting that 0-degree positioning may be an appropriate change to the standard of care for stroke patients before thrombectomy.
  • Head positioning is considered a manoeuvre to maintain blood flow for patients awaiting surgical intervention, not a stroke treatment itself.

Positioning patients with large vessel ischaemic (clot-caused) stroke with their heads flat (0-degrees) before surgery to remove the blood clot resulted in significant improvements in neurological function, compared to patients whose heads were elevated (at a 30-degree angle), according to science presented on February 7th at the American Stroke Association’s International Stroke Conference 2024. The meeting was held in person in Phoenix, Arizona, February 7 – 9, 2024.

Large vessel occlusion is a type of ischaemic stroke involving blockage of a major artery in the brain. A surgical procedure called thrombectomy removes the blood clot to restore blood flow and reduce the risk of death or permanent injury to the brain including a potential loss of neurological function.

“Many thrombectomy patients have delays until the procedure can be started, whether due to slow internal hospital processes, multiple patients arriving at the same time or if the patient needs to be transferred to another hospital. Optimising blood flow to the brain while patients are waiting for surgery, is essential to minimise the risk of neurological deficits and ultimately disability.” 

Anne W. Alexandrov, Ph.D., Lead Study Research and Professor of Nursing and Neurology at the University of Tennessee Health Science Center in Memphis

Currently, hospital beds for stroke patients awaiting thrombectomy surgery are typically set with the head of the bed at a 30-degree angle, or a slight incline, Alexandrov said. However, pilot studies conducted by Alexandrov’s team have shown that when the head of the bed is flat at 0-degrees, thrombectomy patients benefit from increased gravitational blood flow through the narrowed/blocked artery and more open collateral arteries for the procedure. 

In this randomised clinical trial called Zero Degree Head Positioning in Acute Large Vessel Ischemic Stroke or ZODIAC, researchers used the National Institutes of Health Stroke Scale (NIHSS) — which assesses consciousness, vision, speech, motor strength and sensory loss —  to evaluate stroke patients with large vessel occlusion acute ischaemic stroke. They compared if patients’ conditions remained stable or worsened depending on whether they were set with 0-degree head positioning vs. 30-degree head positioning before thrombectomy surgery.

Stroke patients’ baseline NIHSS scores were measured at 0-degrees immediately after neuroimaging, then they were randomly positioned to head positioning at either 0-degrees or 30-degrees. Patients underwent repeat NIHSS scoring every 10 minutes until the thrombectomy was performed, with a final NIHSS score assessed immediately before they were positioned on the surgical table.

An interim analysis found that 0-degree head positioning before thrombectomy surgery resulted in greater stability and/or clinical improvement prior to surgery based on repeated NIHSS scores in stroke patients compared to patients with 30-degree head positioning.

The investigators also explored whether there would be differences in the NIHSS score at 24 hours following surgery and at 7 days or discharge (whichever came first), however, they didn’t expect to find a difference because thrombectomy itself dramatically improves patient outcomes. They were surprised to find that at both 24 hours after surgery and at 7 days after discharge, the 0-degree-head-position patients had less neurological deficits on the NIHSS compared to patients with head-positioning at a 30-degree incline before surgery.

“By three months following surgery, there was no difference in outcomes for patients in either group, however, it’s exciting to see that we were able to discharge patients from the hospital with less disability requiring rehabilitation,” Alexandrov said.

Due to the efficacy of 0-degree head positioning for stroke patients awaiting thrombectomy, the study’s Data and Safety Monitoring Board stopped enrollment in this trial on November 1, 2023.

“Our findings suggest that gravitational force can play an important role in improving blood flow temporarily while patients are waiting for surgery,” Alexandrov said. “Zero-degree head positioning is a safe and effective strategy to optimise blood flow to the brain until the thrombectomy can be performed, and it should be considered the standard of care for stroke patients prior to thrombectomy.”

Abstracts presented at the American Heart Association’s scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

Non-pharmacological migraine treatment

Posted on February 23, 2024 by - Headache

Theranica’s REN Wearable Becomes the First Ever Non-Pharmacological Migraine Treatment to Receive Commercial Coverage in the USA

Feb. 20, 2024: Theranica, a prescribed digital therapeutics company specialising in neuromodulation devices for migraine and other idiopathic pain conditions, announced the inclusion of its Nerivio Remote Electrical Neuromodulation (REN) wearable, for use in the acute and preventive treatment of migraine, under a commercial coverage policy of Highmark Inc (Highmark). This follows the successful completion of its Coverage with Evidence Development (CED) programme with Nerivio, launched in November 2022. The new commercial coverage policy marks a significant advancement in the accessibility of an effective, non-disruptive, and non-pharmacological migraine treatment.

Professor Christopher Gottschalk, MD, FAHS, Neurology Division Chief and Director of the Headache & Facial Pain Center at Yale University and the President of the Alliance for Headache Disorders Advocacy (AHDA), welcomed this coverage policy: “Americans with chronic conditions like migraine have faced a longstanding need for insurance coverage of neuromodulation devices and other non-pharmacological treatments. Nerivio is an evidence-based treatment that is supported by well-controlled trials, and this coverage policy is an encouraging milestone. We at the AHDA have high hopes that other US commercial insurers and Federally funded insurance plans will follow the very sensible footsteps of Highmark and recognise the importance of providing the 40 million Americans living with migraine with affordable access to drug-free prescription migraine treatments with clinical benefits properly backed by high-quality data.”

Highmark’s coverage decision for the Nerivio REN wearable follows a rigorous CED study with the device, assessing its clinical benefits over 384 members living with migraine. In the primary endpoint of the study, Nerivio demonstrated statistically significant results in the reduction in Migraine Disability Assessment Score (MIDAS) from 64.0 to 43.9 points (p<0.005). Additional clinically meaningful benefits were demonstrated with 75.8% of the participants experiencing pain relief within 2 hours post-treatment, 37.3% reporting pain freedom, 69.0% indicating functional disability relief, and 52.4% specifying full return to functional ability post 2 hours.

The CED study shows statistically significant and clinically meaningful benefits to migraine patients treated with the REN wearable in a real-world environment. This data highlights the importance of including REN among migraine therapies covered by insurance to address the unmet need for effective, safe, easy-to-use migraine intervention.”

Andrea Synowiec, DO, FAAN, Vice Chair of the Department of Neurology at Allegheny Health Network in Pennsylvania, Primary Investigator

Is Long COVID a brain injury?

Posted on February 19, 2024 by - COVID-19 Articles

Study led by Benedict Michael finds global cognitive deficits

A recent study on Preprint server Research Square suggests that brain fog, memory and concentration problems may be due to brain injury caused by the COVID-19 virus.

The study found that 351 patients hospitalised with severe COVID-19 had evidence of a long-term brain injury a year after contracting the SARS-CoV-2 virus – this was compared against 2,927 healthy controls. These findings were based on cognitive tests, self-reported symptoms, brain scans, and biomarkers. 

More than 60% of COVID-19 survivors display persistent symptoms even months or years following recovery from the primary infection, significantly impacting their quality of life.

Treatment with corticosteroids during the acute phase appeared protective against cognitive deficits. The study authors suggest that “These findings support the hypothesis that brain injury in moderate to severe COVID-19 is immune-mediated, and should guide the development of therapeutic strategies.”

Potential treatments for secondary brain cancer

Posted on February 7, 2024 by - Brain tumours

Drugs already licensed could be trialled to potentially treat secondary brain cancer, new research finds

The largest review of papers for brain cancer that has spread from the lungs has found abnormalities in the brain cancer. Licensed drugs could be clinically trialled to find out if they could treat the disease. The research led by the University of Bristol and published in Neuro-Oncology Advances also found genetic differences between smokers and non-smokers.

Around 25,000 patients in the UK suffer from cancer that has spread to the brain – known as metastases – most commonly from lung and breast cancer, and which causes death in the majority of these patients.

The genetic mutations in primary lung cancers have been widely studied, but less is known about the changes in the cancer once it has spread to the brain. The research team wanted to find out the genetic changes in brain metastasis from non-small cell lung cancer (NSCLC) and whether there are drugs already available that could potentially be offered to these patients.

The researchers carried out a review from 72 papers of genetic mutations in brain metastasis of NSCLC from 2,346 patients’ data on patient demographics, smoking status, genomic data, matched primary NSCLC, and PD-L1, which is a protein found on cancer cells.

The study found the most commonly mutated genes were EGFR, TP53, KRAS, CDKN2A, and STK11.  Common missense mutations —mutations that lead to a single amino acid change in the protein coded by the gene— included EGFR L858R and KRAS G12C

In certain cases the genetic mutations were different in the brain metastasis from the primary lung cancer. There were also differences in the genetic mutations in smokers versus patients who had never smoked. Brain metastases of smokers versus non-smokers had different missense mutations in some mutated genes.

The research team found from the top ten commonly mutated genes which had primary NSCLC data, 37% of the specific mutations assessed were different between primary NSCLC and brain metastases. The researchers suggest Medicines and Healthcare products Regulatory Agency-approved drugs already licensed could potentially be tested to treat the disease in clinical trials.

Kathreena Kurian, Professor of Neuropathology and Honorary Consultant at North Bristol NHS Trust, Head of the Brain Tumour Research Centre at the University of Bristol and co-author of the paper, said: “Our research recommends that all patients should have their brain metastasis examined for mutations in addition to their primary lung cancer because they may be different.

“This evidence could form the backbone for new clinical trials for patients with brain metastasis in non-small cell lung cancer using drugs that are already available.”

Our research recommends that all patients should have their brain metastasis examined for mutations in addition to their primary lung cancer because they may be different. This evidence could form the backbone for new clinical trials for patients with brain metastasis in non-small cell lung cancer using drugs that are already available.

Kathreena Kurian

The research was funded by Cancer Research UK; Southmead Hospital Charity: Brain Tumour Bank Research (fund 8036); Innovate UK; and the National Institute for Health and Care Research (NIHR). 

Kathreena Kurian is Chair of the Bristol Cancer Research Network, which is supported by Elizabeth Blackwell Institute.

Paper

‘Genomic landscape and actionable mutations of brain metastases derived from non-small cell lung cancer: a systematic review‘ by Lily J Andrews, Kathreena M Kurian et al. in Neuro-Oncology Advances [open access]

Immune response responsible for neurological damage

Posted on February 6, 2024 by - Neuroimmunology

There has been a long-held belief that acute viral infections are directly responsible for neurological damage, but researchers from McMaster University have now discovered that it is the immune system’s response that is behind it.

The research, published on February 5, 2024 in Nature Communications, was led by Elizabeth Balint, a PhD student at McMaster, and Ali Ashkar, a Professor with the Department of Medicine and the Canada Research Chair in Natural Immunity and NK Cell Function.

“We were interested in trying to understand why so many viral infections are associated with neurological diseases,” says Balint. “Our evidence suggests that it’s not the virus itself that causes the damage, but a unique population of T cells, which are part of the immune system, that are actually responsible for the damage.”

Our evidence suggests that it’s not the virus itself that causes the damage, but a unique population of T cells, which are part of the immune system, that are actually responsible for the damage.

Elizabeth Balint, a PhD student at McMaster University

To come to this conclusion, the McMaster team focused on Zika virus. During laboratory testing, researchers, as expected, found T cells that were specific for Zika and designed to eliminate infected cells. They found something else, too.

“What was interesting in our study is that although we did find some T cells specific for Zika, we identified cells that weren’t functioning like a normal T cell and were killing lots of cells that weren’t infected with Zika.”

These cells are called NKG2D+CD8+ T cells and researchers say their aggressive response is responsible for neurological damage suffered from infections beyond just Zika, like COVID-19 and even septic shock.

The aggressive response is the result of the body producing large amounts of inflammatory proteins called cytokines, which in moderation help to coordinate the body’s response in battling an infection or injury by telling immune cells where to go and what to do when they arrive.

“If our body’s immune cells overreact and over produce inflammatory cytokines, this condition will lead to non-specific activation of our immune cells which in turn leads to collateral damage. This can have severe consequences if it happens in the brain,” Ashkar says.

The discovery offers researchers and scientists a new target for treatments of neurological diseases sparked by acute viral infections. In fact, Balint has already found a treatment that holds promise.

“Elizabeth has experimented with an antibody that can completely block and treat devastating neurotoxicity in the animal model, which is already in clinical trials  for different uses in humans,” says Ashkar.

Balint hopes to continue her work towards finding a treatment that would be effective in humans.

“There are a few different other viruses we’re interested in studying, which will aid us in creating the best treatment options,” Balint says.

Funding for this study was provided by the Canadian Institutes of Health Research. Balint is also a recipient of a Canada Graduate Scholarship Doctoral Award.

Biogen drops Alzheimer’s drug Aduhelm

Posted on February 1, 2024 by - Alzheimer's Disease

31 January 2024; Biogen has announced that it will discontinue the development and commercialisation of ADUHELM® (aducanumab-avwa) 100 mg/mL injection for intravenous use and will terminate the ENVISION clinical study. This decision is not related to any safety or efficacy concerns. A large portion of the resources released resulting from termination of the ADUHELM programme will be redeployed in Biogen’s AD franchise.

We plan to further advance the launch of LEQEMBI, together with Eisai, and continue to bolster innovation with the development of the other assets in our pipeline. When searching for new medicines, one breakthrough can be the foundation that triggers future medicines to be developed. ADUHELM was that groundbreaking discovery that paved the way for a new class of drugs and reinvigorated investments in the field.”

Christopher A. Viehbacher, President and Chief Executive Officer of Biogen

In January 2023, Biogen began a strategic review of its research and development efforts, including seeking potential partners or external financing for ADUHELM, as part of a focus on prioritising the company’s portfolio. During this process, Biogen considered the time and investment required for the post-marketing confirmatory ENVISION study and the likely advancements in the field by the time of potential ADUHELM FDA traditional approval. Despite an extensive process, the company did not identify potential strategic partners or external financing.

“We have gained significant insight from the development of ADUHELM and will carry this forward as we continue our pioneering work in Alzheimer’s disease,” said Priya Singhal, M.D., M.P.H., Head of Development at Biogen. “We’d like to sincerely thank the trial investigators, healthcare providers, advocates, patients and families involved in the development of ADUHELM. We are grateful to Neurimmune for its scientific contributions and collaboration over many years.”

ADUHELM received accelerated approval from the U.S. Food and Drug Administration in June 2021. The Phase 4 post-marketing confirmatory ENVISION study was a requirement of FDA accelerated approval of ADUHELM.

Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai and Biogen commercialising and co-promoting the product and Eisai having final decision-making authority.