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The chief executive officer and founder at CureDuchenne discussed efforts to bring specialized physical therapy and infrastructure support to underserved regions to improve care for patients impacted by Duchenne worldwide. [WATCH TIME: 5 minutes]

Helping to Expand Global Care for the Duchenne Muscular Dystrophy Patient Community: Debra Miller

Neurology News Network. for the week ending September 7, 2024. [WATCH TIME: 4 minutes]

Tolebrutinib Shows Promise in Non-Relapsing Secondary Progressive MS, Fenebrutinib Suppresses Relapses in New Data, FDA Accepts Resubmitted NDA for AXS-07

Articles

Take 5 minutes to catch up on NeurologyLive®'s highlights from the week ending September 6, 2024. 

NeurologyLive® Friday 5 — September 6, 2024

Treatment with DYNE-251 revealed dose dependent exon skipping and dystrophin expression as well as improvement in multiple functional end points in both cohorts of the phase 1/2 DELIVER trial.

DYNE-251 Increases Dystrophin Level Expression in Phase 1/2 DELIVER Trial of Duchenne

, has been with the team since October 2019. Follow him on Twitter 

Tanya, a patient who lost her mobility due to undiagnosed spinal issues, discussed her life-saving surgery for spinal meningioma, and the complex surgical process she underwent to regain her strength.

Treating Rare Cases of Spinal Meningioma Using Complex Surgical Tactics

Mind Moments®, a podcast from NeurologyLive®, brings you an exclusive interview with Imad Najm, MD, PhD. [LISTEN TIME: 22 minutes]

Episode 123: Previewing Cleveland Clinic's Epilepsy Summit

The director of Cleveland Clinic’s Epilepsy Center at the Cleveland Clinic Neurological Institute provided commentary on the future outlook of gene therapies for patients with epilepsy, and some of the knowledge and technical barriers clinicians currently face. [WATCH TIME: 5 minutes]

Promise and Potential Challenges With Gene Therapy in Epilepsy: Imad Najm, MD

The director of neurology and neuromuscular medicine at the Children’s Hospital of the King’s Daughters in Norfolk, Virginia, provided clinical perspective on some of the improvements in the everyday life and care of patients with spinal muscular atrophy.

NeuroVoices: Crystal Proud, MD, on SMA Awareness Month, Advances in Research and Treatments

NeurologyLive is your direct connection to the latest neurology news and interviews with expert neurologists in multimedia formats.

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Director of the Brain Health Observatory at the University of Southern California.

The director of the Brain Health Observatory at the University of Southern California discussed how blood tests for Alzheimer disease could significantly reduce diagnostic wait times and improve treatment monitoring. [WATCH TIME: 4 minutes]

Impact of Blood Tests on Wait Times and Treatment in Alzheimer Disease: Soeren Mattke, MD, DSc

The director of the Brain Health Observatory at the University of Southern California discussed the potential impact of Alzheimer disease blood tests on reducing clinic wait times and improving the diagnostic process in primary care.

NeuroVoices: Soeren Mattke, MD, DSc, on Utilizing Blood Tests to Reduce Wait Times and Improve Diagnosis in Alzheimer Disease

The director of the Brain Health Observatory at the University of Southern California talked about integrating blood tests into primary care to better triage patients with Alzheimer disease, reduce unnecessary referrals, and shorten appointment wait times. [WATCH TIME: 7 minutes]

Improving Alzheimer Disease Diagnosis Through Efficient Referrals of Blood Tests: Soeren Mattke, MD, DSc

In a phase 1, 2-part, open-label, fixed-sequence, single and multiple oral dose study newly published in 

Clinical Pharmacology in Drug Development

, results showed that the pharmacokinetics of vatiquinone (PTC Therapeutics) a small molecule inhibitor of 15-lipoxygenase in development for patients with Friedreich ataxia (FA), can be adjusted by coadministration of cytochrome P450 isoform 3A4 (CYP3A4) inhibitor itraconazole or CYP3A4 inducer rifampin.

Coadministration of vatiquinone 400 mg with itraconazole 200 mg increased maximum observed concentration (C

) of vatiquinone and systemic exposure (AUC

) by approximately 3.5- and 2.9-fold, respectively. The coadministration of vatiquinone 400 mg with rifampin 600 mg decreased vatiquinone C

 by approximately 0.64- and 0.54-fold, respectively. Notably, the terminal half-life of vatiquinone was not influenced by neither itraconazole or rifampin.

“Vatiquinone has demonstrated a very well-established safety profile in children, including very young children with severe illnesses, as well as in adults in clinical studies," Matthew B. Klein, MD, MS, FACS, chief executive officer at PTC Therapeutics, told 

. "The pharmacology results shared in the publication should not impact the exposure, safety, or use of vatiquinone but can provide guidance for physicians when considering other medications that patients may be receiving."

In this study, investigators assessed the effect of itraconazole and rifampin on the single-dose PKs of vatiquinone. Researchers enrolled participants between 18 and 45 years of age, with a body mass index of 18.5-30 kg/m2. On the first day of each part of the study, patients only received a single dose of vatiquinone 400 mg, which was followed by a washout of 7 days. In Part 1, patients received itraconazole on days 8 through 11, and they received vatiquinone coadministered with itraconazole on day 12, followed by a last dose of itraconazole on day 13. In Part 2, patients received rifampin on days 8 through 21, and then received vatiquinone coadministered with rifampin on day 22, followed by a last dose of rifampin on day 23.

“The clinical study results confirm that the CYP3A4 enzyme plays an important role in vatiquinone metabolism and the effect on vatiquinone PK when coadministered with a potent CYP3A4 inhibitor or inducer. Additional work was performed to understand the impact of moderate CYP3A4 inhibitors and inducers on vatiquinone exposures via physiologically based pharmacokinetic modeling and will be presented elsewhere,” coauthor Lee Golden, MD, chief medical officer at PTC Therapeutics, and colleagues wrote.

Specific Biomarkers Detected for Staging and Treatment in Spinocerebellar Ataxia Type 3

Although 3 patients (13.04%) reported 4 treatment-emergent adverse events (TEAEs), investigators observed no treatment-emergent serious adverse events (TESAEs) during the study. Only 2 participants experienced temporary clinically significant elevations in hepatic enzymes. As for the reported TEAEs, they were in the Gastrointestinal System Organ Class (SOC) and, for 1 patient, also in the Nervous System SOC. 

Authors noted that all TEAEs were mild and resolved by the completion of the study or shortly thereafter. The reported TEAES were considered unrelated to vatiquinone although the elevated alanine transaminase and aspartate transaminase enzymes might have possibly been related to itraconazole, according to the principal investigator of the study.

“The results of this analysis together with phase 3 efficacy and safety data, population PK analysis, and the exposure-response relationship will determine if the extent of vatiquinone changes in the presence of CYP3A4 inhibitors and inducers are considered clinically relevant,” Golden et al noted.

 According to a recent company update, PTC Therapeutics has plans to submit a new drug application (NDA) for vatiquinone for the treatment of FA in late 2024.

2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference

, held March 3-6, in Orlando, Florida, data from the placebo-controlled phase of the global phase 3 MOVE-FA trial (NCT04577352) assessing vatiquinone in patients with FA showed the treatment demonstrated clinically relevant benefits across multiple end points at 72 weeks.

In the analysis, investigators observed a –1.61 (

=.144) change in modified FA Rating Scale (mFARS)compared with the placebo at 72 weeks in the modified intent-to-treat (mITT) population, which consisted of 123 participants with FA. The researchers reported a sustained vatiquinone treatment benefit observed across all end points including the primary, secondary, and exploratory end points.

"The recently completed MOVE-FA placebo-controlled study results demonstrate a statistically significant and meaningful effect on the upright stability subscale of the disease rating scale – the most relevant and sensitive component of the disease rating scale for pediatric and young adult ambulatory patients," Klein said. "The results in the study support that vatiquinone could have an important effect in delaying loss of ambulation as well as other important and burdensome aspects of the disease."

Conducted by lead author David Lynch, MD, PhD, a neurologist and director of the Friedreich's Ataxia Program at Children's Hospital of Philadelphia, and colleagues, the trial included patients 143 aged at least 7 years, with an mFARS score of between 20 and 70 and the ability to ambulate at least 10 feet in 1 minute with or without assistance. The primary end point of the current analysis was placebo-corrected change from baseline in mFARS at 72 weeks. The intent-to-treat (ITT) population had a mean age of 18.7 years and the primary analysis population—the mITT population—included participants between 7 years and 21 years of age (mean, 14.6).

Investigators observed a nominally significant benefit recorded in the Upright Stability subscale (USS), a relevant metric of disease progression in younger ambulatory patients with FA, of mFARS, with a change of –1.26 (

 = .021). In addition, researchers observed nominally significant benefit in the Modified Fatigue Impact Scale, with a change of –5.05 (

 = .025). Overall, the authors noted that the treatment was safe and well tolerated among the participants, with no differences in treatment-related adverse events observed between treatment and placebo groups.

"The effects observed in this trial along with the established safety profile will form the basis of the planned vatiquinone NDA submission later this year," Klein added.

REFERENCES
1. Lee L, Thoolen M, Ma J, Kaushik D, Golden L, Kong R. Effect of Itraconazole, a CYP3A4 Inhibitor, and Rifampin, a CYP3A4 Inducer, on the Pharmacokinetics of Vatiquinone. Clin Pharmacol Drug Dev. Published online August 12, 2024. doi:10.1002/cpdd.1461
2. PTC Therapeutics Provides Corporate Update and Reports Second Quarter 2024 Financial Results. News Release. PTC Therapeutics. August 8, 2024. Accessed August 22, 2024. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-provides-corporate-update-and-reports-second-2
3. Lynch D, Duquette A, França MC, et al. Safety and Efficacy of Vatiquinone Treatment in Friedreich Ataxia Patients from MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Poster S79.

PTC Therapeutics has plans to submit a new drug application for vatiquinone, a small molecule inhibitor of 15-lipoxygenase in development for patients with Friedreich ataxia, in late 2024.

Clinical

Vatiquinone Pharmacokinetics Influenced by CYP3A4 Inhibitors and Inducers in Phase 1 Study

, a cell-based assay (CBA) developed by researchers allowed the testing of novel neuron-/astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in routine laboratories. This CBA, using neurons and astrocytes derived from human-induced pluripotent stem cells (hiPSCs), can potentially open new viewpoints in establishing a diagnosis of complex diseases such as neuromyelitis optica spectrum disorder (NMOSD).

Using this 96-well CBA, investigators identified antibodies that recognized hiPSC-derived neural cells in 19 out of 99 patients. Antibodies were attached particularly to astrocytes in 9 cases, to neurons in 8 cases, and to both cell types in 2 cases, which were confirmed by microscopy single-cell analyses. Investigators observed that neural-specific antibody binding was more frequent in patients with inflammatory neurological diseases (IND, n = 15) compared with those who had non-IND (NIND, n = 4) (Fisher's exact test,

= .0005), further highlighting the significance of their comprehensive CBA.

"Our CBA using human iPSC-derived neurons and astrocytes allows to detect antibodies that would not be identified by traditional approaches. Indeed, these human central nervous system (CNS) cells naturally express antigens with the appropriate post-translational changes, which is not always the case with other methods reported to date. So, in the future, we envision that this CNS CBA has its place in the cases where an autoimmune neurological condition is strongly suspected, yet traditional detection assays give negative results,” senior author Renaud Du Pasquier, MD, told 

For instance, up to 46% of auto-immune encephalitis (AIE) and up to 16% of NMOSD are seronegative with current traditional assays. So, our CBA, by ascertaining the diagnosis of AIE or NMOSD in some patients, may decrease the area of uncertainty and thus help the physician in therapeutical management."

All told, human iPSC-derived astrocytes or neurons were incubated with serum/CSF from 42 patients with IND and 57 patients with non-IND. Researchers noted that the IND group had 11 patients with established neural antibodies prior, 6 with seronegative NMOSD, 12 with suspension of autoimmune encephalitis/paraneoplastic syndrome (PNS), and 13 with other IND. Immunoglobulin G (IgG) binding to fixed CNS cells was identified utilizing fluorescently-labeled antibodies and evaluated by automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Authors used peripheral blood mononuclear cells (PBMC) as CNS-irrelevant control target cells. Researchers defined reactivity profile as positive through a Robust regression as well as an outlier removal test with a false discovery rate at 10% following each patient readout.

Interim Analysis Confirms Satralizumab's Safety and Efficacy in Japanese Patients With NMOSD

Investigators also observed that 2 out of the 4 patients with aquaporin-4 antibody positive (AQP4+) NMOSD and 4 of 7 definite AIE/PNS with intracellular-reactive antibodies, as detected in diagnostic laboratories, tested also positive with the CBA. Notably, authors demonstrated antibody-reactivity in 2 out of the 6 patients who were seronegative NMOSD, 6 of 12 probable AIE/PNS, and 1 of 13 other IND. Flow cytometry utilizing hiPSC-derived CNS cells or PBMC-identified antibody binding among 13 patients versus no patients, respectively, which established the specificity of the recognized antibodies in the neural tissue.

"One of the most difficult aspects was establishing reliable protocols to generate large numbers of hiPSC-derived astrocytes and neurons. These protocols are needed to ensure consistency and high cell quality across experiments and different teams," Du Pasquier, who serves as a full professor and the head of the neurology department at CHUV/University of Lausanne, said. "After rigorous optimization, we successfully created protocols that consistently produce high-quality CNS cells. These protocols are now used by collaborators and other research teams worldwide, ensuring standardization and reliability across various labs."

"Another significant hurdle was automating the detection of antibody reactivity through fluorescence measurements including microscopy assessments. This step is crucial for determining whether autoantibodies in serum or CSF bind to astrocytes or neurons. Such optimization enables us to generate reliable results within a few days," Du Pasquier added.

Authors noted that this current CBA is limited to only astrocytes and neurons; thus, they underscored that other CNS cell types including oligodendrocytes, microglia, endothelial or even ependymal cells could be an asset to broaden the antigenic diversity. Researchers argued the previous research showed that astrocytes and neurons presently cover the majority of CNS antigens associated with neurological disorders expect for myelin oligodendrocyte glycoprotein antibody disease, which is express by oligodendrocytes.

"An advantage of our CBA is that it offers the potential to precisely characterize new antigens that would be expressed exclusively in human brain cells. Once such an antigen is defined, it will be possible to transfect it into HEK cells and implement those cells into routine diagnostic tests. Overall, by broadening the number of antigens recognized by antibodies in autoimmune neurological diseases, our CBA may improve clinical management of patients affected by these severe conditions,” Du Pasquier said.

REFERENCES
1. Mathias A, Perriot S, Jones S, et al. Human stem cell-derived neurons and astrocytes to detect novel auto-reactive IgG response in immune-mediated neurological diseases. Front Immunol. 2024;15:1419712. Published 2024 Jul 24. doi:10.3389/fimmu.2024.1419712
2. Sechi E, Flanagan EP. Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management. Front Neurol. 2021;12:673339. Published 2021 Jul 7. doi:10.3389/fneur.2021.673339
3. Hamid SHM, Whittam D, Mutch K, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017;264(10):2088-2094. doi:10.1007/s00415-017-8596-7

Research indicated that up to 46% of patients diagnosed with presumed autoimmune limbic encephalitis tested negative for all currently identified central nervous system antigens.

Novel Cell-Based Assay Enhances Detection of Autoantibodies in Neurological Disorders

Anna Castagna, MD, stressed how new clinical trial designs for cervical dystonia should incorporate more flexible and patient-centered approaches.

The Need for Flexibility and Patient-Centered Approaches in Clinical Trials for Cervical Dystonia: Anna Castagna, MD

"If a patient has difficulties after one treatment they must be reassured that it is possible to be reinjected when they perceive the wearing off effect, even if it is before the considered time."

Patients with cervical dystonia treated with botulinum toxin, a first-line therapy for this condition, typically require injections every 3 to 4 months. The consistency of botulinum toxin's effect is important for maintaining the patients' quality of life, as it helps prevent fluctuations in symptom control between injections. However, there is currently no standardized method for clinicians to assess the duration of botulinum toxin's effect in patients with cervical dystonia in a clinical setting.

A recent scoping review performed by lead author 

, and colleagues summarized available evidence from phase 3 clinical trials assessing botulinum toxin in cervical dystonia and interpretation of the reported duration of its effect. In the review, studies showed that clinical trial outcomes in cervical dystonia were not assessed objectively, and did not prioritize the needs of patients or focus on factors that impacted their daily living activities and quality of life. Authors therefore noted that there is a need for better evidence and consistency of reports for duration of effect for botulinum toxin in cervical dystonia to guide providers on when reinjection is likely to be essential.

These findings were presented at the 3rd Annual 

Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress

 from June 22-25, 2024, by Castagna, a consultant neurologist at Fondazione Don Carlo Gnocchi ONLUS in Milan, Italy. Recently, Castagna sat down with 

 to discuss how the integration of patient-centered measurement scales can improve the outcomes of clinical trials for cervical dystonia. She also talked about the potential benefits and challenges of using mobile apps to monitor the effectiveness and duration of cervical dystonia treatments. Moreover, Castagna spoke about how the flexibility in reinjection schedules may impact patient outcomes and overall treatment effectiveness in real-life settings.

Click here for more coverage of ATMRD 2024

REFERENCES
1. Castagna A, Jinnah HA, Albanese A. Duration of botulinum toxin efficacy in cervical dystonia clinical trials: A scoping review. Parkinsonism Relat Disord. 2024;125:107011. doi:10.1016/j.parkreldis.2024.107011

The consultant neurologist at Fondazione Don Carlo Gnocchi ONLUS stressed how new clinical trial designs for cervical dystonia should incorporate more flexible and patient-centered approaches, including new measurement scales and the use of technology. [WATCH TIME: 5 minutes]

Differentiating patients with atypical parkinsonisms from idiopathic Parkinson disease (PD) can be a significant challenge for clinicians in clinical practice because of the similar symptoms presented in each of them. For instance, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) exhibit an overlap of pathological features and have various phenotypic variants. Therefore, it is important for providers to make an accurate diagnosis to determine the most effective treatment and management approach for patients. Prior research even indicated that inappropriate treatment, because of misdiagnosis, provides limited benefits to patients, complicating care and increasing the disease burden.

, delivered a presentation on diagnostic insights in atypical parkinsonism. He discussed methods for clinicians to differentiate the clinical and pathological features of each atypical parkinsonian syndrome from idiopathic PD. Additionally, he highlighted key indicators that may signal atypical parkinsonism and evaluated recent advancements in diagnostics and treatments.

, Shprecher, the director of movement disorders at the Banner Sun Health Research Institute, sat down with 

 at the Congress to discuss the current limitations of diagnostics tests such as the Syn-One skin biopsy test and cerebral spinal fluid (CSF) test for synuclein biomarkers. Shprecher, who also serves as a clinical associate professor at University of Arizona-Phoenix, spoke about how the current biomarkers help differentiate between synucleinopathies and tauopathies. Furthermore, he talked about future developments anticipated in minimally invasive biomarker testing for neurodegenerative diseases.

NeurologyLive: Could you provide an overview of your talk that you presented at ATMRD on diagnostic pearls and atypical Parkinson?

First of all, thanks so much for your interest in the ATMRD program. I was able to kick off the symposium today with the first CME talk in diagnostic pearls and atypical Parkinsonism. I also touched briefly on some of the updates and diagnostic criteria for atypical Parkinsonian disorders and some of the clinical pearls and management. It's an exciting time because we're just at the cusp of having biomarkers that can help us more reliably differentiate what the underlying changes in the nervous system are while patients are still alive, when it really matters to them.

What are the main takeaways from your talk that clinicians should be thinking about regarding developments in diagnostics?

While the data is very promising for synuclein biomarkers—both the Syn-One skin biopsy test and the CSF test from Amperon—we still don't have studies that compare patients with synucleinopathy to those with tauopathies and some of these other proteinopathies. We still need a little bit more time to study the utility of these tests in differentiating some of those tough cases. [In addition,] we want to recognize the limitations of the data sets that are still out there. That said, the synuclein biomarker in the Parkinson Progression Markers Initiative (PPMI) showed extraordinarily high sensitivity, 99%, in clinically well-defined patients with PD who also had anosmia using the University of Pennsylvania smell identification test. We were able to very clearly identify classic patients with PD that show misfolded alpha-synuclein in the CSF that can be confirmed during life with a test that isn't terribly invasive, but we would like something a little less invasive, if possible.

Another important limitation there is we still don't know in other cohorts where patients present with the classic “not reading the textbook” approach to things where they don't have all of the classic features of PD. What's the utility attest in those cases? We don't have any autopsy confirmed cohorts yet, so there are still some limitations. Another thing to emphasize with this, and also with the Syn-One biopsy test, is that we do have 2 well defined, relatively large cohorts for both biomarkers but these studies haven't necessarily been confirmed by independent groups with separate cohorts and separate labs. 

When it comes to the Syn-One biopsy test, an important limitation is that all of the participants enrolled were very well defined patients with synucleinopathies, PD, dementia with Lewy bodies, pure autonomic failure, and multiple system atrophy. There were no patients with some of the other atypicals, the tauopathies, for example. In addition, there were very well defined healthy controls, but the healthy controls, on average, were younger than the disease patients. That is a limitation of the data. Still, it is a useful test in select cases, but we really need to understand the limitations of the test. That is just another piece of information. It's not a simple yes or no answer either you have synucleinopathy or you don't and that there isn't anything else going on.

What other developments for enhanced diagnostics should the clinical community look forward to?

We really would like to see tests that are minimally invasive, that could be therefore more broadly available and broadly utilized. If the Syn-One biopsy test could be studied in a much larger cohort, such as the PPMI cohort, that would be very helpful. I would be very excited to see that happen. I think another area that would be super exciting—if it can happen—is if we could have a blood biomarker, of course, for synucleonopathy, or even for tauopathy, that would be what we consider our most minimally invasive test, other than maybe an imaging ligand. We're still a ways off from a synuclein imaging ligand.

Are there any closing remarks that you have regarding your presentation and regarding the Congress?

There are 2 imaging ligands just to keep an eye on. First of all, there is a synuclein imaging ligand that, while it doesn't necessarily differentiate all synucleinopathies, does show promise specifically separating multiple system atrophy from the other synucleinopathies. Another exciting development is we have several different tau ligands in development. Some are mainly being developed for Alzheimer disease, but one in particular from Molecular Life Sciences is also showing promise because of a different pattern of deposition in PSP. Where it clearly differentiates people with the classic presentation of Richardson syndrome from, say, PD or healthy controls. This is now being studied in a much larger cohort of neurodegenerative disease patients who are all at end of life and also consented for brain autopsy. Hopefully, over the next few years, we’ll have autopsy-confirmed data about the utility of this ligand for identifying these 4 repeat telepathies like PSP or CBD during life, when it matters the most to our patients.

REFERENCES
1. McFarland NR. Diagnostic Approach to Atypical Parkinsonian Syndromes. Continuum (Minneap Minn). 2016;22(4 Movment Disorders):1117-1142. doi:10.1212/CON.0000000000000348

The director of movement disorders at the Banner Sun Health Research Institute talked about recent, promising advancements for diagnosing atypical Parkinsonian disorders and the questions that remain.

NeuroVoices: David Shprecher, DO, MSci, FAAN, on Current and Future Directions in Biomarker Testing for Atypical Parkinsonism

According to a recent announcement, the FDA has granted the approval of Myogenica’s investigational new drug (IND) application to study MyoPAXon, an induced pluripotent stem cell-derived muscle stem cell product to regenerate skeletal muscle. The company noted that a proposed early-stage clinical trial would assess the safety, tolerability, and engraftment of the therapy among patients with Duchenne muscular dystrophy (DMD).

, a pediatric neuromuscular neurologist and director of the Greg Marzolf Jr. Muscular Dystrophy Center at the University of Minnesota Medical School, plans to administer intra-muscular injections of MyoPAXon in adult patients with nonambulatory DMD. Kang and colleagues in the trial will then monitor any potential site reactions or immune response and investigate the presence of dystrophin-producing myofibers.

"I was thrilled to see this milestone in testing cell therapies for muscular dystrophy in humans. There is enormous potential to provide lasting relief for patients with muscular dystrophy. Our planned initial study will focus on safety considerations, and we will be injecting MyoPAXon into a small foot muscle to assess safety and tolerability of various doses," Kang told 

. "What makes MyoPAXon distinct is that it has the exciting potential for muscle regeneration. Once injected, the MyoPAXon cells can survive indefinitely and thus yield long term beneficial effects."

Myogenica noted in the announcement that Kang and colleagues will initiate mid-stage study targeting other muscles and evaluating muscle function if the proposed trial produces positive findings. Since MyoPAXon is not specific for any genetic mutation, it may have the potential use as a treatment for a range of other muscular dystrophies as well as other muscle degenerative conditions, according to the company.

Gaps in Follow Up and Sustained Clinical Care Observed in Pediatric Muscular Dystrophy

Clinical translation of MyoPAXon is a culmination of years of interdisciplinary teamwork at the University of Minnesota, involving the lab of 

, the Molecular and Cellular Therapeutics cGMP facility, the Center for Translational Medicine, and the Greg Marzolf Jr. Muscular Dystrophy Center. Duchenne UK contributed over $900,000 to fund the IND-enabling studies of MyoPAXon in addition to cofunding the proposed clinical trial. The project also had funding provided by the Department of Defense, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, MyDirectives, and the Greg Marzolf Jr. Foundation.

"Pure excitement and joy. We have worked intensely on this project for the last 7 years so we were overjoyed with the news from the FDA," Perlingeiro, the cofounder of Myogenica and the Lillehei professor in stem cell and regenerative cardiovascular medicine at the University of Minnesota, told 

when asked about her reaction to the news.

"We hope MyoPAXon will contribute to new and healthy muscle in DMD, and other types of MD in the near future. The main goal of the current trial is safety, but a secondary outcome is detection of dystrophin to confirm production of new donor-derived healthy myofibers."

"MyoPAXon is an universal allogeneic stem cell product. Therefore, MyoPAXon's application is not restricted to a subset of DMD mutations, which is a major differential from other current investigational therapies for patients with DMD,"  Perlingeiro added. "Accordingly, MyoPAXon's therapeutic application goes beyond DMD, as it has the potential to contribute to healthy muscle regeneration in other types of muscular dystrophies and muscle degenerative conditions. In addition, differently from gene therapy, MyoPAXon is not limited to one single time injection."

2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference

, held March 19-22, in Dallas, Texas, Perlingeiro presented a talk on the potential of using iPS cells in the treatment of muscular dystrophy. In addition to her talk, the session also focused on the use of patient-specific iPS cells to model neuromuscular diseases, with the goal of understanding disease pathogenesis and treatment development. Also, the session emphasized the expansion of bioengineering approaches for skeletal muscle modeling.

, Perlingeiro provided an overview of some of the main highlights addressed. She also spoke about the challenges and unmet needs of this patient population that have started to gain attention, as well as the potential of iPS in regenerative medicine.

Rita Perlingeiro, PhD, talked about the potential of investigating inducted pluripotent stem cells in neuromuscular diseases at MDA’s 2023 conference.

Clinical Application of Induced Pluripotent Stem Cells in Muscular Dystrophy: Rita Perlingeiro, PhD

REFERENCES
1. FDA Clears Investigational New Drug application for muscular dystrophy treatment from University of Minnesota startup Myogenica. News Release. Myogenica. Published July 17, 2024. Accessed July 23, 2024. https://prnmedia.prnewswire.com/news-releases/fda-clears-investigational-new-drug-application-for-muscular-dystrophy-treatment-from-university-of-minnesota-startup-myogenica-302199393.html
2. Perlingeiro R. Using patient-specific iPS cells to model and target FKRP mutations. Presented at: MDA Clinical & Scientific Conference; March 19-22, 2023; Dallas, TX. Using iPS Cells to Model Neuromuscular Disease session.

Pending positive results from an early-stage trial, a mid-stage study evaluating MyoPAXon’s effect on other targeted muscles and muscle function will be initiated.

FDA Clears IND Application for Myogenica’s MyoPAXon in Muscular Dystrophy

 (CCF)'s Parkinson's Inpatient Program comprises of system and patient level interventions aimed to promote recovery in patients with Parkinson disease (PD). System level interventions took place at both enterprise and individual hospital levels. Enterprise level changes comprised electronic health record modifications including best practice alerts and notification of PD contraindicated medications. Hospital level interventions included creation of a PD inpatient census, a dedicated PD inpatient consult team, clinician education, changes in PD medication stocking/administration, and changes to Speech Therapy documentation templates.

 was an efficient and effective way to correctly identify and prevent or correct common clinical errors that could lead to lesser outcomes and further complications in hospitalized patients with PD.

Patricia Clark, CNP, a nurse practitioner at the Cleveland Clinic, talked about a specialized program for hospitalized patients with Parkinson disease that aligns hospital protocols with home medication regimens to improve care.

Soeren Mattke, MD, DSc

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