Author: Rachael Hansford

Gut bacteria and PD

Posted on October 11, 2023 by - Parkinson’s Disease

Could changes in gut bacteria contribute to the development of Parkinson’s disease in those with genetic risk?

Via World Parkinson’s Congress: Mutations in the GBA1 gene are one of the most common genetic risk factors associated with Parkinson’s disease (PD). However, it’s important to note that not all people with GBA1 mutations will necessarily develop PD. Furthermore, if they do, the onset may occur at different ages and with different clinical presentations. This variability highlights the critical need to identify additional factors, both environmental and genetic, that may influence the likelihood of developing PD in individuals with GBA1 mutations.

Individuals with GBA1-related PD often have a higher prevalence of non-motor symptoms, such as a reduced sense of smell and constipation, which typically precede the onset of motor symptoms. The characteristic tremors, rigidity, slowness of movement, and freezing in PD have been attributed to the loss of certain brain cells called dopaminergic neurons, along with the accumulation of a protein called α-synuclein in the brain. A hypothesis emerged in 2003 that the initial pathology of α-synuclein may originate in the gastrointestinal tract before progressing to the brain. Specifically, people with PD often have alterations in their gut microbiota, resulting in changes in the maintenance of the intestinal lining, inflammation, and the body’s ability to defend itself against invading pathogens.

The research laboratory of Christin Weissleder, PhD is investigating how GBA1 mutations might interact with microbial molecules to promote inflammation and α-synuclein accumulation using various cell culture systems. Read more.

Watch the Hot Topics presentation on this subject from WPC 2023.

UK-wide research platform for brain injury treatment

Posted on October 10, 2023 by - Acquired Brain Injury

TBI-REPORTER, a new research platform led by the University of Cambridge, will bring together leading experts to enable better and more coordinated research into traumatic brain injury. It is hoped that this will result in more people receiving appropriate treatment due to better forecasting of how a particular injury is likely to impact a patient with TBI.

The platform will focus on research into populations previously underserved, including unhoused people, prisoners and those who have experienced domestic violence. 

Collaborating for better outcomes

TBI-REPORTER, standing for UK-TBI REpository and data PORTal Enabling discoveRy, is a new initiative supported by key UK health and research organisations, including the National Institute for Health and Care Research (NICE), the Medical Research Council (MRC), the Ministry of Defence (MOD), and Alzheimer’s Research UK.

The brain injury research platform will bring together data from existing research into brain injury and work closely with the UK Biobank and Dementias Platform UK to coordinate new investigations with the aim of accelerating our understanding of traumatic brain injury, commonly known as TBI. 

TBI-REPORTER is also developing a network of hospitals and other institutions specialising in neuroscience, all prepared to explore new methods of diagnosing and treating traumatic brain injuries.

It is a privilege to lead this ambitious platform, which brings together a breadth of experts and draws on the lived experience of TBI survivors and their families, to improve care of traumatic brain injury. We also believe that our work, in combination with that of international partners, will re-energise drug development in TBI and deliver new treatments for patients.

Professor David Menon, Head of the Division of Anaesthesia at the University of Cambridge and Project lead

Read more.

Positive CHMP opinion for generalised myasthenia gravis treatment

Posted on September 29, 2023 by - Myasthenia Gravis

UCB receives CHMP positive opinion of zilucoplan for the treatment of adults with generalised myasthenia gravis in Europe

  • The Committee for Medicinal Products for Human Use (CHMP) positive opinion1 is based on the pivotal Phase 3 RAISE study in generalised myasthenia gravis (gMG) in adult patients which demonstrated that treatment with zilucoplan resulted in statistically significant and clinically meaningful improvements in gMG-specific efficacy outcomes2
  • If approved by the European Commission, zilucoplan will be the first once-daily subcutaneous (SC) targeted peptide inhibitor of complement component 5 (C5 inhibitor) and the only gMG-targeted therapy for self-administration by adult patients with AChR antibody positive gMG
  • CHMP positive opinion in Europe follows recent FDA approval of rozanolixizumab-noli for the treatment of generalized myasthenia gravis (gMG) in adult patients in the U.S. who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive3
  • UCB’s two different medicines for gMG, each with a distinct mechanism of action, aim to offer a unique portfolio of treatments that embody our commitment to addressing the gMG community’s unmet needs

15 September 2023 – UCB, a global biopharmaceutical company, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending granting marketing authorisation for zilucoplan in the European Union (EU) as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti acetylcholine receptor (AChR) antibody positive.1

The CHMP’s positive opinion is now being reviewed by the European Commission, which grants centralised marketing authorisations for medicinal products in the EU. Feedback from the commission is anticipated before the end of the year. 

Following approval, zilucoplan will be the first once-daily subcutaneous (SC), targeted peptide inhibitor of complement component 5 (C5 inhibitor) and the only self-administered gMG therapy for use by adult patients with AChR antibody positive gMG.

As a C5 inhibitor, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted dual mechanism of action.2 Benefits of SC self-administration can include reduced traveling time to and from hospitals, decreased interference with work obligations, and increased independence. Unlike monoclonal antibody C5 inhibitors, as a peptide, zilucoplan can be used concomitantly with intravenous immunoglobulin and plasma exchange, without the need for supplemental dosing.2

UCB’s RAISE study2, published earlier this year in the Lancet Neurology journal, demonstrated that zilucoplan delivered rapid, consistent, statistically significant and clinically meaningful benefits in different patient-and-clinician-reported outcomes – Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Composite (MGC) score and Myasthenia Gravis Quality of Life 15-item scale (MG-QoL15r)* – at week 12 in a broad population of mild to severe adult patients with AChR antibody positive gMG. Additionally, rapid improvements in fatigue were observed as an exploratory endpoint. 

Until now, people living with gMG have only had access to C5 therapy intravenously, which can be inconvenient and time-consuming. This positive CHMP opinion for zilucoplan is a significant step towards our goal of delivering a treatment to address the unmet needs of people living with gMG. If approved, we hope zilucoplan, a self-administered, once daily, subcutaneous targeted C5 inhibitor, will be able to help a broad population of mild to severe adult patients with AChR-antibody positive gMG. We would like to extend our thanks to the patients, care partners, and investigators who participated in the RAISE study, and to our employees and collaborators, whose dedication and commitment to the gMG community made this important milestone possible.

Iris Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB.

gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterised by dysfunction and damage at the neuromuscular junction (NMJ).4,5,6 gMG has a global prevalence of 100–350 cases per every 1 million people.5 

The CHMP positive opinion recommending the approval of zilucoplan is supported by safety and efficacy data from the Phase 3 RAISE study (NCT04115293), published in The Lancet Neurology in May 2023.2 The primary endpoint for the RAISE study was change from baseline to Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. A statistically significant and clinically meaningful difference favouring zilucoplan in comparison to placebo was observed in the MG-ADL total score change from baseline: least squares mean change −4·39 [95% CI –5·28 to –3·50] vs −2·30 [–3·17 to –1·43], least squares mean difference −2·09 [−3·24 to −0·95]; p=0·0004. Secondary endpoints included change from baseline to Week 12 in QMG, MGC and MG-QoL15r. A statistically significant and clinically meaningful difference favoring zilucoplan compared to placebo was observed in the QMG total score change from baseline to Week 12 (p<0.0001), least squares mean change −6.19 [95% CI −7.29 to −5.08] vs −3.25 [−4.32 to −2.17]. Change from baseline to Week 12 in MGC in comparison to placebo was clinically meaningful and statistically significant. MG-QoL 15r change from baseline to Week 12 compared to placebo was also statistically significant.2 Change from baseline to week 12 in the Neuro-QoL short-form fatigue scale was an exploratory end point, therefore, p value was nominal, not multiplicity controlled.

The most common adverse events (reported in at least 10% of patients treated with zilucoplan) were injection-site bruising, headache, diarrhea and MG worsening.2

Zilucoplan is also currently under review by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), the U.S. Food and Drug Administration (FDA), the Australian Therapeutic Goods Administration (TGA) and Health Canada for the treatment of adults with gMG. Responses from the PMDA and FDA are expected by the end of Q4 2023. Responses from the TGA and Health Canada are expected by H1 2024. Orphan designation was granted by the European Commission in 2022 to zilucoplan for the treatment of myasthenia gravis.7 
    
The CHMP positive opinion of zilucoplan follows the recent FDA approval in the U.S. of rozanolixizumab-noli for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive3. Rozanolixizumab-noli is currently only approved in the U.S. and is under review by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines Agency (EMA) for the treatment of adults with gMG. Responses from regulatory agencies to these submissions are expected during H2 2023 and H1 2024.

* The threshold for clinical meaningfulness for MG-QoL 15r has not be established

References

  1. EMA CHMP Confirmation. Data on file, UCB September 2023.
  2. Howard JF Jr et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22:395-406. 
  3. US Food and Drug Administration. Novel Drug approvals for 2023. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2023. Accessed September 2023.
  4. National Institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-sheet. Accessed September 2023.
  5. Punga AR, et al. Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders. Lancet Neurol. 2022;21(2):176-88.
  6. Howard JF. Myasthenia gravis: The role of complement at the neuromuscular junction. Ann N Y Acad Sci. 2018;1412:113-128.
  7. European Medicines Agency. EU/3/22/2650: Orphan designation for the treatment of myasthenia gravis. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-22-2650. Accessed August 2023
  8. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasthenia.org/MG-Education/MG-Quick-Facts. Accessed September 2023.
  9. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44.

Phase 3 Study Results Compare IPX203 to Immediate-Release Carbidopa/Levodopa for PD

Posted on August 31, 2023 by - Parkinson’s Disease

IPX203 demonstrated statistically significant improvement in daily “Good On” time compared to optimised IR CD/LD, with fewer daily doses

August 24th, 2023: Amneal Pharmaceuticals, Inc announced that JAMA Neurology has published results from the RISE-PD clinical study assessing the efficacy and safety of IPX203 versus optimised immediate-release carbidopa/levodopa (IR CD/LD) for the treatment of Parkinson’s disease (PD). The study met its primary and secondary endpoints finding that IPX203 provided more hours of “Good On” time per day, less “Off” time per day, and more “Good On” time per dose than optimised IR CD/LD, even when dosed less frequently. “Good On” time is defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia. The manuscript titled, “IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease,” was published online on August 14, 2023.

When it comes to Parkinson’s disease, the community is looking for treatments that provide a longer duration of benefit per dose of LD and simplified dosing regimens. We are very encouraged by the recently published data in JAMA Neurology which illustrate how IPX203 could fill this need, potentially leading to a better patient experience, more ‘Good On’ time, and improved patient adherence.

Robert A. Hauser, M.D., Professor of Neurology at the University of South Florida and Director of the Parkinson’s Disease and Movement Disorders Center.

Following a Complete Response Letter (CRL) from the FDA earlier this year on its New Drug Application for IPX203, Amneal has shared a reanalysis of the data and requested a Type A meeting as it looks to bring the treatment to market.

About the RISE-PD Trial

The multicenter, randomised, double-blind, double-dummy, active-controlled, parallel-group RISE-PD trial evaluated the efficacy and safety of IPX203 CD/LD extended-release capsules compared with IR CD/LD in the treatment of patients with PD who have motor fluctuations.

The trial consisted of a 3-week, open-label immediate-release CD/LD dose adjustment period and a 4-week, open-label period for conversion to IPX-203. This was followed by a 13-week double-blind treatment period in which patients were randomised 1:1 to receive either IPX203 (with matching immediate-release CD/LD placebo) optimised IR CD/LD (with matching IPX-203 placebo). Baseline for all endpoints was Week 7 (Visit 4), which occurred pre-randomisation. The most common adverse reaction (incidence ≥ 3% and greater than immediate-release CD/LD) was nausea (4.3%).

The primary endpoint of the trial assessed the change from baseline in “Good On” time in hours per day at the end of the double-blind treatment period (Week 20 or early termination). “Good On” time is defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia. Secondary endpoints assessed the change from baseline in “Off” time in hours per day, proportion of patients who were either “much improved” or “very much improved” in Patients’ Global Impression of Change (PGI-C) scores, change from baseline in the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score, and the change from baseline in sum of MDS-UPDRS Parts II and III scores.

The trial was conducted at 105 clinical sites in the U.S. and European countries, including Czechia, France, Germany, Italy, Poland, Spain and the United Kingdom. The study randomised 506 patients who had received a PD diagnosis at age 40 or older. The study design was reviewed by the FDA and conducted pursuant to a Special Protocol Assessment. A nine-month safety extension study was completed in 2022.

Brain stimulation project could treat wide range of neurological disorders

Posted on August 30, 2023 by - Neurology News

21st August, 2023

Researchers from the University of Glasgow, UK are part of a cross-Europe project which is aiming to develop a revolutionary new method of treating a wide range of neurological disorders.

The Wireless Deep Brain Stimulation Through Engineered Multifunctional Nanomaterials project, or BRAINSTORM, is setting out to develop tiny injectable magnets which could help restore function to damaged neurons in patients’ brains. 

The BRAINSTORM team hope that their research could treat, or even cure, conditions like depression, panic attacks, epilepsy, Alzheimer’s disease or Parkinson’s disease.

The nanoscale magnets the team will develop will eventually be injected into rodents’ bloodstreams in a preclinical study and controlled using external magnets to deliver neurostimulation to specific neurons in their brains. 

Neurostimulation, which uses electrical currents or magnetic fields to modulate the activity of nerves or neural circuits, is already in use to treat a variety of brain-related conditions, often accompanied by surgeries to implant the electrodes which deliver the treatments. 

Over the next four years, researchers from the University of Glasgow will partner with colleagues from Germany, Italy, Spain and Finland to develop the BRAINSTORM technology, which could deliver improved results with less invasive techniques.

The project is supported by €3m (£2.57m) from the European Innovation Council’s Pathfinder programme. The Pathfinder programme provides funding for researchers to develop emerging breakthrough technologies.

Hadi Heidari, Professor of Nanoelectronics at the James Watt School of Engineering, is leading the University of Glasgow’s contribution to BRAINSTORM. 

He and his team at the School’s Microelectronics Lab will develop a wearable helmet-like device that will use magnets to control the positioning of nanomaterials, enabling neuromodulation treatments to be precisely targeted in the brain.

Neuromodulation is a treatment that has shown a great deal of potential for treating many conditions. However, our present methods of delivering neuromodulation can require invasive surgeries to implant electrodes, which can be expensive, painful and expose patients to an increased risk of infection. 

Hadi Heidari, Professor of Nanoelectronics at the James Watt School of Engineering

“BRAINSTORM is an exciting new opportunity to rethink how wireless neuromodulation is delivered. It builds on recent advances in magnetic coil nanofabrication, materials science and medicine to allow us to find new ways to precisely ‘switch on’ or ‘switch off’ neuronal activity for therapeutic effects. 

“I’m pleased to be working with my colleagues across Europe on this research, and I’m looking forward to developing some of the key technologies which will help patients benefit from new treatments in the years to come.”

BRAINSTORM Is led by Professor Danijela Gregurec of the Friedrich-Alexander-Universität Erlangen-Nürnberg in Germany. Researchers from CIC biomaGUNE in Spain, Tor Vergata University in Italy, and the University of Helsinki in Finland are contributing to the project along with the University of Glasgow. 

For more information on BRAINSTORM, visit https://www.brainstorm-project.eu

Can the scent of essential oils improve memory?

Posted on August 29, 2023 by - Alzheimer's Disease, Cognition

From Medscape, August 8th 2023.

Inhaling a pleasant aroma during sleep has been linked to an improvement in memory, small-scale early research suggests. Researchers randomly assigned 43 older adults, aged 60 – 85 years, to receive either nightly exposure to essential oil scents delivered via a diffuser (n = 20; mean [SD] age, 70.1 [6.6] years) or to a sham control with only trace amounts of odorants (n = 23; mean age, 69.2 [7.1] years) for a period of 6 months.

They found that when cognitively normal individuals were exposed to the scent of an essential oil for 2 hours every night over 6 months, they experienced a 226% improvement in memory compared with a control group who received only a trace amount of the diffused scent. A caveat is that several measures of cognitive function were assessed and only one (verbal memory) showed clear improvement. In addition, functional magnetic resonance imaging (fMRI) showed that those in the enriched group had improved functioning of the left uncinate fasciculus, an area of the brain linked to memory and cognition, which typically declines with age.

The study was published online on July 24th in Frontiers of Neuroscience. It concluded “Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health.”

Ketogenic diet in RRMS

Posted on August 8, 2023 by - Multiple Sclerosis

Study suggests benefits may be long lasting

Following a ketogenic diet for six months significantly reduced measures of body fat and fatigue, eased disease symptoms, and improved exercise capacity, cognition, and arm and hand dexterity in people with relapsing-remitting multiple sclerosis (RRMS), a study has shown. The research, Ketogenic diet in relapsing multiple sclerosis: Patient perceptions, post-trial diet adherence & outcomes, was published in the journal Clinical Nutrition.

Some benefits lasted for at least three months after the study ended, though several measures worsened – mainly due to difficulties in maintaining a strict ketogenic diet in the real world. 58% followed the diet after the trial ended, according to the data.

Following the 6-month KD intervention study, the majority of subjects elected to continue on KD, though many pursued a more liberal limit for carbohydrate restriction. Those who experienced a greater reduction in BMI or fatigue were more likely to continue with strict KD. The 6-month KD intervention induced persistent changes to dietary habits in the months following study completion.

Oxygen for brain injuries – can it help patients?

Posted on August 3, 2023 by - Acquired Brain Injury

Inhaling oxygen while learning a motor task helped healthy people learn more quickly and effectively, raising hopes for neurorehabilitation 

Scientists studying the impact of oxygen supplementation on motor learning have found a promising treatment that could help patients who have experienced neurological trauma recover old skills. “A simple and easy to administer treatment with 100% oxygen can drastically improve human motor learning processes,” said Dr Marc Dalecki, now at the German University of Health and Sports in Berlin, senior author of the study in Frontiers in Neuroscience.

In high-oxygen contexts cognitive function recovers, and the delivery of 100% oxygen is already used to help preserve as much of the brain as possible in patients with neurological injuries. Motor learning is particularly dependent on oxygen-reliant information processing and memory functions: humans learn by trial and error, so the ability to remember and integrate information from previous trials is critical to efficient and effective motor learning. So could supplementing oxygen while learning a motor task help people learn faster and more effectively, offering hope for neurorehabilitation patients? 

“I had this idea in my mind for almost a decade and promised myself to investigate it once I got my own research lab,” said Dalecki, who led the experimental research at the School of Kinesiology at Louisiana State University. “And with Zheng Wang, now Dr Zheng Wang, I had the perfect doctoral student to run it – a keen physiotherapist with a clinical background and stroke patient experience.”  

Dalecki and Wang recruited 40 participants, 20 of whom received 100% oxygen at normobaric pressure and 20 of whom received medical air (21% oxygen) through a nasal cannula during the ‘adaptation’ or learning phase of a task. Dalecki and Wang selected a simple visuomotor task which involved drawing lines between different targets on a digital tablet with a stylus: the task was designed to test how quickly the participants were able to integrate information from the eye and hand, a crucial part of motor learning. After the task had been learned, the alignment of the cursor and the stylus was altered to see how effectively the participants adapted to the inconsistency, and then realigned for a final session to see how they adapted to the realignment. 

“The oxygen treatment led to substantially faster and about 30% better learning in a typical visuomotor adaptation task,” said Wang, first author of the study and now at the Mayo Clinic in Rochester. “We also demonstrate that the participants were able to consolidate these improvements after the termination of the oxygen treatment.”

The scientists found that the participants who had received oxygen learned faster and performed better, improvements which extended into later sessions of the task when oxygen was not administered. The oxygen group moved the pen more smoothly and more accurately, and when the cursor was adjusted in a deliberate attempt to throw them off, they adapted more quickly. They also made bigger mistakes when the alignment of the stylus was corrected, suggesting they had integrated the previous alignment more thoroughly than the other group. 

Dalecki and Wang plan to investigate the long-term effects of this supplementation on learning and test the intervention with other motor learning tasks: it is possible that the relevant brain functions for this task in particular benefit from high ambient oxygen levels, leading to the observed advantages in performance. They also hope to bring the oxygen treatment to elderly and injured people, in the hope that it will help them re-learn motor skills.

Our future plan is to investigate whether this treatment can also improve motor recovery processes following brain trauma. Since it worked in the young healthy brain, we expect that the effects may even be larger in the neurologically impaired, more vulnerable brain.

Dr Marc Dalecki

Epilepsy associated with CDKL5 Deficiency Disorder

Posted on August 2, 2023 by - Epilepsy

European Commission Approval of ZTALMY® (ganaxolone) for the Adjunctive Treatment of Epileptic Seizures Associated with CDKL5 Deficiency Disorder

31 July 2023: Marinus Pharmaceuticals announced that the European Commission (EC) has granted approval of ZTALMY® (ganaxolone) oral suspension for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients two to 17 years of age. ZTALMY may be continued in patients 18 years of age and older. ZTALMY is the first treatment approved by the European Commission for seizures associated with CDKL5 deficiency disorder in children and adolescents.

The EC approval of ZTALMY in CDD is supported by data from the Phase 3 Marigold double-blind placebo-controlled trial, in which 101 patients were randomised and individuals treated with ZTALMY showed a median 30.7% reduction in 28-day major motor seizure frequency, compared to a median 6.9% reduction for those receiving placebo, achieving the trial’s primary endpoint (p=0.0036). In the Marigold open label extension study, patients treated with ZTALMY for at least 12 months (n=48) experienced a median 49.6% reduction in major motor seizure frequency. In the clinical development programme, ZTALMY demonstrated efficacy, safety and tolerability with the most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) in the ZTALMY group being somnolence, pyrexia, salivary hypersecretion and seasonal allergy. In May 2022, the results from the Marigold study were published in The Lancet Neurology.1

The approval follows a positive opinion issued in May 2023 by the Committee for Medicinal Products for Human Use of the European Medicines Agency and is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. In July 2021, Marinus and Orion Corporation entered into a collaboration agreement which grants Orion the right to commercialise ZTALMY in Europe.

The approval by the European Commission represents a significant milestone for children, families and physicians who, until now, have long been challenged by the impact of seizures and lack of treatments available for CDD. This achievement reflects our organisation’s unwavering commitment to bring an effective treatment option to individuals living with CDD and we are grateful to all the stakeholders who made the approval possible.

Scott Braunstein, M.D., Chairman and Chief Executive Officer of Marinus

References

1 The Lancet Neurology, Volume 21, Issue 5, P417-427, May 01, 2022

2 Olson H et al. 2019 Pediatric Neurology

3 Jakimiec M et al. 2020 Brain Sci.

About CDKL5 Deficiency Disorder

CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder characterised by early‑onset, difficult‑to‑control seizures and severe neuro‑developmental impairment.2 It is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. The CDKL5 gene produces a protein that is important for normal brain development and function.3

About ZTALMY®

ZTALMY (ganaxolone) is a neuroactive steroid GABAA receptor modulator that acts on a well-characterised target in the brain known to have anti-seizure effects. ZTALMY is an oral prescription medicine approved by the European Commission for the adjunctive treatment of epileptic seizures associated with CDKL5 deficiency disorder in patients two to 17 years of age. ZTALMY may be continued in patients 18 years of age and older.