This program is supported by educational grants from argenx. 

To obtain CME credit, visit https://checkrare.com/learning/p-beyond-achr-recognizing-and-treating-musk-ab-lrp4-ab-and-triple-seronegative-myasthenia-gravis/

This accredited CME program examines best practices for diagnosing and treating patients with ultra-rare forms of myasthenia gravis. The most prevalent form of myasthenia gravis is associated with antibodies against the acetylcholine receptor (AChR Ab+). However, 15- 20% of patients with myasthenia gravis are not AChR Ab+. These clinically important and underrecognized subsets of patients have antibodies against muscle-specific kinase (MuSK Ab+), lipoprotein receptor-related protein 4 (LRP4 Ab+), or test negative for all known antibodies (triple seronegative MG). These patients present unique diagnostic and treatment challenges that necessitate the need for experts to provide guidance that can improve how these patients are better managed.

Led by Drs. Neelam Goyal and Christyn Edmundson, this activity used case studies involving three different patients suspected of having MuSK Ab+, LRP4, Ab+ and Triple Seronegative Myasthenia Gravis to discuss how they assess those patients, diagnose them properly, and decide which treatment option is most appropriate for that patient. 

Target Audience
This activity has been designed to meet the educational needs of physicians specializing in neurology, ophthalmology, rheumatology, and family practice. Other members of the care team may also participate.

Learning Objectives

• After participating in the activity, learners should be better able to:
• Describe the current hypotheses regarding disease mechanisms in MuSK Ab+, LRP4 Ab+, and triple seronegative MG and apply this mechanistic understanding to diagnostic reasoning and treatment planning.
• Recognize the subtype-specific clinical features of MuSK Ab+, LRP4 Ab+, and triple seronegative MG and apply an appropriate diagnostic workup
• Identify patients with MuSK Ab+, LRP4 Ab+, or triple seronegative MG who are suboptimally controlled on traditional therapies and apply subtype-specific evidence to guide timely transition to newer therapies.
• Articulate the distinct treatment burden and disease progression patterns in MuSK+, LRP4+, and triple seronegative MG and apply treatment goals that reflect the potential benefits of targeted over traditional therapy.

Neelam Goyal, MD
Clinical Professor, Neuromuscular Medicine
Stanford University
Stanford, CA

Christyn Edmundson, MD
Neurologist
Swedish Neuroscience Institute 
Seattle, WA

Disclosure Statement
According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.

Disclosure of relevant financial relationships are as follows:

Faculty Educator/Planner
Dr. Goyal discloses the following relevant financial relationships with ineligible companies:
Advisory Board/Consultant: argenx, Alexion, UCB, Janssen, Amgen, Novartis, Immunovant*, Dianthus, Seismic*, Cartesian*, EMD Serono* (*Relationship has ended)
Research Grant: argenx

Dr. Edmunson discloses the following relevant financial relationships with ineligible companies:
Advisory Board/Consultant: Alnylam, Alexion, Amgen, argenx, Kyverna, UCB
Speaker’s Bureau: Alnylam, Alexion, Amgen, argenx, UCB

Academy and CheckRare CE planners and reviewers for this activity have no relevant financial relationships with any ineligible companies.

This activity will review off-label or investigational information.

The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.

Accreditation and Credit Designation
In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physicians
American Academy of CME, Inc., designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit com...

0 0

Christine Gustafson, Executive Director and CEO of the TED Community Organization, discusses the new Graves’ Community website.

Graves’ disease is an autoimmune disease characterized by generalized overactivity of the thyroid gland. Thyroid eye disease (TED) and Graves’ are usually comorbid conditions. Graves’ disease affects approximately 1% to 2% of the adult population, with an estimated 40% of patients subsequently developing TED over the course of their lifetime.

Recently, the TED Community Organization launched a new Graves’ Disease website as a companion to their TED website, an initiative aimed at reconnecting Graves’ disease and TED in the minds of patients and physicians. The two conditions were separated by Horizon/Amgen for marketing purposes about 6 years ago, however around 95% of TED patients also have Graves’.

The website focuses on providing trusted, patient-centered education under the TED Community umbrella. Main themes include helping people better understand Graves' disease, recognizing the connection between Graves' disease and TED, exploring treatment options, following emerging research, and discovering reliable resources from the beginning of the patient journey.

Graves’ disease also has some upcoming medical research, including novel biologic therapies designed to address the underlying autoimmune mechanisms that drive Graves' disease. While these investigational treatments are still being studied in clinical trials, they represent a new era of scientific discovery and renewed hope for patients and families. Patients can stay up to date with this clinical research on the new website.

Visit the new website at gravescommunity.org

CHAPTERS
Introduction 00:00
Bringing Graves’ and TED Back Together 1:34
Risk of Developing TED 5:24
Advice for Newly Diagnosed Patients 8:17
Key Takeaway 13:33

0 0

Neil Inhaber, MD, FRCPC, Therapeutic Area Head of Global Medical, Rare Disease at Takeda, discusses data on maribavir in post-transplant cytomegalovirus (CMV) presented at the American Transplant Congress 2026.

Post-transplant CMV is one of the most common infections following a solid organ transplant (SOT), which can lead to risk of graft loss and death. CMV is a ubiquitous herpes virus that infects up to 60−100% of people in adulthood, and it is one of the main agents involved in infectious complications after transplantation. Similarly to other herpes viruses, CMV establishes a latent infection after initial infection. In the immunocompetent host, the initial infection is generally asymptomatic but may present as an unspecified febrile, flu-like or mononucleosis-like syndrome. In rare cases, the infection presents as a systemic syndrome, affecting many organs. Additionally, immunocompetent adults may present a clinical syndrome later in life due to reactivation of latent virus or due to new infection by another viral strain. The disease caused by post-transplant CMV (PT-CMV) occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative transplant patients.

Efficacy of Maribavir in Solid Organ Transplant Recipients with and without Neutropenia: A Post Hoc Analysis of Phase 2 Data

The goal of this analysis was to assess the safety and efficacy of maribavir, an anti-CMV agent with lower incidence of myelosuppression, in SOT recipients with and without baseline neutropenia. A post hoc analysis was conducted from a phase 2, dose-ranging study in 120 SOT and hematopoietic cell transplant recipients with refractory/resistant (RR) CMV infection (NCT01611974).

In total, the analysis included 73 SOT recipients who received 1 or more doses of maribavir. At baseline, 14 patients had neutropenia and 59 did not. Baseline characteristics and safety data were similar between SOT recipients with and without neutropenia. There was no significant difference in time to CMV clearance in those with or without neutropenia at baseline.

Real World Effectiveness and Safety of Maribavir in Solid Organ Transplant (SOT) Recipients with Refractory/Resistant Cytomegalovirus or Intolerance to Anti-Cytomegalovirus Drugs: Interim Results from ARISE

The goal of this analysis was to assess maribavir use, effectiveness, and safety for the treatment of post-transplant CMV infection in routine practice.

ARISE is a retrospective cohort study evaluating maribavir use in adult transplant recipients with RR CMV or intolerance to anti-CMV agents in 10 European countries. Interim results were recently presented.

The analysis included 124 SOT recipients. Overall, 47 patients experienced 1 or more CMV episodes before the index episode (first maribavir-treated episode). In patients with available viral load (n=79), CMV clearance at maribavir discontinuation was achieved by 62% RR and 88% intolerant patients. During the index episode maribavir monotherapy was the first treatment agent in 28% patients and second in 53%. Median duration of maribavir treatment course was 57 and 56 days in RR and intolerant patients, respectively, with 60% of treatment course discontinuations due to CMV episode resolution. Maribavir was initiated at home in 71% RR patients and 44% intolerant patients. In patients whose index episode ended, Kaplan-Meier estimates of recurrence 56 or less days from maribavir discontinuation were 39% and 27% in the RR and intolerant groups. Most common adverse events included myelosuppression, nephrotoxicity, and taste disturbance.

CHAPTERS
Introduction 00:00
Addressing Unmet Needs 00:49
Real-World Data Developments 6:19
Treatment Challenges 8:28

1 0

Sanofi is currently facing supply chain issues, including in their treatments for Pompe disease and hemophilia. An FDA inspection in January highlighted several quality control concerns at a manufacturing plant in Ireland, and in June the FDA followed up with a letter stating that these concerns had not been addressed. While the plant is still open, they are making significant changes to the site to be compliant. Sanofi is doing its best to get therapies back to patients, but the patients are very frustrated about the lack of transparency and the lack of a back up manufacturing plant.

2 0

Tracey Dawson, PhD, Senior Vice President, US Therapeutic Area Head Neuroscience at Novartis, discusses the collaboration between Novartis, SMAshing My Limits, and Becoming rentABLE, striving to make travel accessible.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by the loss of motor neurons, causing progressive muscle weakness and loss of movement due to atrophy. SMA is caused by genetic mutations in the SMN1 gene. Extra copies of the nearby related gene, SMN2, modify the severity of SMA, with type 1 being the most severe and type 4 the least severe.

Launched in June 2025, SMAshing My Limits was built around the lived adventures of older teens and young adults living with SMA.

This year, the initiative is evolving to address accessible travel, one of the biggest challenges voiced by the community. Through a partnership with Becoming rentABLE, they are aiming to add 100 new verified short-term rentals to the Becoming rentABLE network across the US that are accessible to persons with SMA. This includes experience-based homes such as treehouses, cabins, yurts, and beachfront properties. Less than 1% of short-term rentals in the US are accessible to wheelchair users, and many lack the full spectrum of features and amenities required for people with SMA. This program aims to decrease safety risks and the emotional toll this can have on people living with SMA and similar conditions.

The campaign features Cory Lee, a travel enthusiast living with SMA. Having traveled to over 50 countries and all 7 continents, Cory has made it his mission to not let his limited mobility impact his passions and dreams. However, the search for truly accessible accommodations still poses a large challenge to any travel plans.

Dr. Dawson advises those who want to make their rental properties more accessible, to visit https://www.becomingrentable.com/ for more information.

To learn more about SMA and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/

0 0

Henry Kaminski, MD, Department of Neurology, and Linda Kusner, PhD, Department of Pharmacology & Physiology at George Washington University, discuss predicting response outcomes with proteomic and machine learning analyses in treating patients with myasthenia gravis (MG).

MG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. It mostly develops in adults but children can also develop this rare condition. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles usually due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

A study published in Springer Nature analyzed serum proteomes collected at baseline from participants in a phase 3 randomized trial comparing thymectomy plus prednisone versus prednisone alone, along with matched controls using liquid chromatography–mass spectrometry.

Due to the variable treatment responses present in patients with MG, there is a need for biomarkers to guide therapeutic decision making. Proteomic profiling, coupled with machine learning, was utilized to offer a hypothesis-free approach to identify multi-protein signatures associated with treatment response.

Results showed that baseline serum proteomes distinguished MG from controls, with pathway enrichment implicating complement activation, immunoglobulin production, and T-cell receptor signaling. Distinct protein panels predicted 6-month clinical improvement within each treatment arm. In the thymectomy-plus-prednisone group, models captured non-linear relationships of predictive proteins in contrast with the predominant additive patterns observed in the prednisone-alone group. Predictive proteins were enriched for T-cell signaling and leukocyte trafficking functions, providing insight into treatment-specific biology.

While Drs. Kaminski and Kusner explain that there is still much work to be done, this method captured core disease characteristics of MG and predicted short-term clinical response in a treatment-specific manner. These findings could enable biomarker-guided selection of treatment, refine risk stratification, and furnish mechanistic readouts for future MG trials and clinical care.

To learn more about gMG and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
What This Study Was Hoping To Answer 00:59
Proteomic And Machine Learning Outcomes 2:19
Different Patient Responses to Treatments 4:28
Implementing This Approach 7:17
What This Could Mean for Patients 8:53
Take Home Message 11:18

0 0

Eric Scheeff, PhD, Chief Scientific Officer at iDefine, discusses the treatment development of RNA amplifiers in patients with Kleefstra syndrome.

Kleefstra syndrome is a rare disorder characterized by developmental delay and intellectual disability, severely limited or absent speech, distinctive facial features, and hypotonia. People with Kleefstra syndrome may also have structural brain abnormalities, congenital heart defects, genitourinary abnormalities, seizures, and a tendency to develop severe respiratory infections. During childhood they may exhibit features of autism or related developmental disorders affecting communication and social interaction. In adolescence, they may develop a general loss of interest and enthusiasm or unresponsiveness. The condition is a haploinsufficiency caused by mutations in the EHMT1 gene or the deletion of a specific region of chromosome 9 that includes EHMT1.

Current treatment options are supportive, such as speech therapy and seizure medications, with no approved treatments targeting the underlying cause of disease. Dr. Scheef explains that these options are inadequately addressing the severity of disease that most patients experience.

iDefine is currently collaborating with Dr. Jeff Coller’s lab at Johns Hopkins University, where RNA amplifiers are being investigated to increase the effectiveness of the one EHMT1 gene present in patients with Kleefstra syndrome. The goal with this technology is to expand into other haploinsufficiencies using a similar mechanism.

To other patient organizations looking to develop their own treatment, Dr. Scheef recommends starting with the underlying biology of disease and building a scientific advisory board. Once that foundation is in place, set the goal of a clinical trial and work backwards to determine what steps need to be taken.

To learn more about potentially partnering with IDefine email [email protected]

For more information on rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/

Kleefstra Syndrome Overview 00:11
Current Treatment Options 1:29
Diagnostic Journey 2:00
Targeted Therapy Development 4:20
Application in Other Indications 5:41
Advice on Drug Development for Advocacy Groups 7:52
Take Home Message 9:13

0 0

FDA approval is a major milestone, but for patients with rare diseases, it is only the beginning. In this episode of The CheckRare Brief, we look at two new rare disease approvals, ongoing drug supply problems affecting patients, and a major acquisition that illustrates how rare disease therapies move from small biotech companies into the hands of larger pharmaceutical companies.

The US Food and Drug Administration (FDA) granted accelerated approval to Ultragenyx’s Genglycos for the treatment of GSD1a. GSD1a is a rare metabolic disorder, caused by mutations in the G6PC gene, that impairs glucose production. The dietary standard of care, uncooked cornstarch every three to six hours, nocturnal feeds, and strict exclusion of fructose, galactose, and sucrose, has sustained life but cannot correct the underlying enzymatic deficiency and is a major burden on patients and caregivers. However, the gene therapy showed a reduction in cornstarch consumption by 30%. Ultragenyx also received a Priority Review Voucher alongside the drug’s approval.

The FDA also approved Pasatru to treat patients with FOP, a disorder in which skeletal muscle and connective tissue are gradually ossified. The approval is based on safety and efficacy data from the phase 3 OPTIMA clinical trial in which Pasatru was found to reduce FOP flare ups by 90%. This marks the second FDA approved treatment for the indication, giving patients and physicians options in their management.

Sanofi is currently facing supply chain issues, including in their treatments for Pompe disease and hemophilia. An FDA inspection in January highlighted several quality control concerns at a manufacturing plant in Ireland, and in June the FDA followed up with a letter stating that these concerns had not been addressed. While the plant is still open, they are making significant changes to the site to be compliant. Sanofi is doing its best to get therapies back to patients, but the patients are very frustrated about the lack of transparency and the lack of a back up manufacturing plant.

Finally, the pharmaceutical company Biomarin bought Alesta, a small biotech company that is developing a treatment for hypophosphatasia. Hypophosphatasia is a rare metabolic disorder that leads to poor mineralization in teeth and bones. Currently, Stensiz is available as an enzyme replacement therapy but there is always a need for patients to have treatment options. The drug Biomarin just bought, ALE1, is in a phase 1/2 study. Details on the trial are currently unknown, but it would appear the data was compelling enough for Biomarin to buy it. This partnership between small biotech and big pharma is seen often in rare diseases. Small biotechs can be very good at discovering and developing a promising drug, but eventually capital, regulatory expertise, manufacturing, and commercial infrastructure are necessary to get these treatments to patients.

References
FDA approves Ultragenyx drug for GSD1a
https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-aged-8-years-and-older-glycogen-storage-disease-type-ia


FDA approves Regeneron drug for FOP
https://www.globenewswire.com/news-release/2026/08/19/3347919/0/en/pasatru-garetosmab-grts-first-and-only-fda-approved-treatment-demonstrating-reduction-in-new-heterotopic-ossification-ho-lesions-and-clinician-assessed-flare-ups-in-a-placebo-contr.html

Sanofi drug supply shortage
https://www.sanofi.com/en/our-science/therapeutic-areas/rare-diseases/supply-update

BioMarin buys third rare disease company in a year
https://www.prnewswire.com/news-releases/biomarin-to-acquire-alesta-therapeutics-to-gain-ale1-a-potential-first-oral-therapy-for-hypophosphatasia-adding-an-important-clinical-program-to-biomarins-pipeline-302854068.html

FDA Extends Review of Capricor’s Deramiocel for DMD
https://www.capricor.com/investors/news-events/press-releases/detail/354/capricor-therapeutics-announces-extension-of-pdufa-target

1 0

In the first episode of the Rare Endocrine Exchange, Margarita Ochoa-Maya, MD, discusses when further diagnostic testing should be done. Learn more about our new podcast and why this conversation matters at https://checkrare.com/multimedia/rare-endocrine-exchange/ or wherever you get your podcasts.

1 0