Rare Discussions

James Howard Jr., MD, Distinguished Professor of Neuromuscular Disease and Professor of Neurology and Medicine at UNC School of Medicine, reviews the treatment landscape for myasthenia gravis.

Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eyes, eyelids, facial expressions, chewing, talking, and swallowing. The condition is usually due to the presence of antibodies against acetylcholine receptors in the neuromuscular junction.

As Dr. Howard explains, due to the variety of ways this rare disease can present, treatment of myasthenia gravis is individualized to each patient based on their specific symptoms and unique comorbidities. In addition, the financial situation of each patient is taken into account.
Acetylcholinesterase inhibitors are often used as bridge therapies. Corticosteroids are also common bridge therapies in younger patients, while steroid sparing agents are more common in older patients or in patients with contraindications to steroids. In patients under the age of 60 with generalized disease and who are anti-acetylcholine receptor (AChR) antibody positive, the removal of the thymus gland is common.

Dr. Howard goes on to discuss approved treatments for myasthenia gravis. In 2017, eculizumab, a complement inhibitor, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

More recently, in December 2021, the FDA approved efgartigimod alfa, an FcRn inhibitor, for the treatment of this same patient population. This approval was based on positive results from the global phase 3 ADAPT trial, which were published in the July 2021 issue of The Lancet Neurology. While Dr. Howard stresses the need for individualized treatment for all myasthenia gravis patients, he is optimistic about the future of FcRn inhibitors in the treatment of myasthenia gravis.

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

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A group of leading experts in metabolic disorders, advocates, and family representatives attended a virtual conference to discuss Type 1 galactosemia.

This roundtable discussion features perspectives from advocates, experts, and families living with Type 1 galactosemia. Galactosemia is a rare genetic disease that can be life-threatening for newborns and cause severe lifelong complications starting as early as the first year of life. Galactosemia affects the body’s ability to make the enzyme that breaks down galactose, a simple sugar produced endogenously by the body that is also found in dairy and other foods, including breast milk. The genetic mutations driving galactosemia cause a toxic buildup of galactose and other metabolites (including Gal-1p and galactitol), which constitutes a medical emergency in newborns and can contribute to lifelong cognitive, neurological, and speech complications, as well as primary ovarian insufficiency in girls and women.

No treatments are currently approved for galactosemia. The current standard of care—a galactose-restricted diet—is insufficient because the body endogenously produces galactose, resulting in the chronic complications mentioned above.

Hosted by the Galactosemia Foundation and Jaguar Gene Therapy, participants included:
- Nicole Casale, President, The Galactosemia Foundation
- Brittany Cudzilo, Vice President, The Galactosemia Foundation
- Gerald T. Berry, MD, Director, Metabolism Program Boston Children’s Hospital and Professor, Harvard Medical School
- Judith L. Fridovich-Keil, PhD, Professor, Emory University School of Medicine
Family Stories by Allison and Brooks Woodfin, Megan and Ava Lilia, and David and DJ Trainor
- May Tobar, Director Patient Advocacy, Jaguar Gene Therapy
- Joe Nolan, CEO, Jaguar Gene Therapy

Nicole Casale and Brittany Cudzilo of the Galactosemia Foundation described the Foundation and its goals, and their experiences with their own children affected by classic galactosemia.
Galactosemia experts Gerard Berry, MD, of Boston Children’s Hospital and Judith Fridovich-Keil, PhD, of Emory University School of Medicine, provided an overview of Type 1 Galactosemia and described the natural history of the disorder and its unmet needs.
The Director of Patient Advocacy at Jaguar Gene Therapy, May Tobar, shared the importance of patient advocacy and why it is important to work closely with the patient community.
Parents of two young patients with Type 1 galactosemia told stories of their children’s diagnoses, and their own experience with classic galactosemia. A 28-year-old patient with classic galactosemia offered his thoughts on living with the disorder and how he meets those challenges every day. His father provided additional perspectives.

The CEO of Jaguar Gene Therapeutics, Joe Nolan, closed the session by thanking all of the participants, including the Galactosemia Foundation, the experts, and the families who shared their personal stories. He also shared a little bit about Jaguar Gene Therapy and the treatment in development for Type 1 galactosemia, JAG101.

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

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This accredited CME activity, led by Barbara Burton, MD, Professor of Pediatrics at Northwestern University Feinberg School of Medicine highlights the latest research about Mucopolysaccharidosis type II (MPS II; Hunter syndrome) presented at WORLDSymposium 2022 and provides expert analysis of its clinical relevance for busy members of the care team to help them care for patients they may encounter with this rare condition.

MPS II; Hunter syndrome is a rare, progressive lysosomal disease caused by deficient activity of iduronate-2-sulfatase, attributable to pathogenic variants of the iduronate-2-sulfatase gene (IDS). Course facial features and skeletal irregularities are the dominant symptoms of the periphery but of great concern is the central symptoms (cognitive decline, seizures) that occur in the more severe cases. Current therapies options include enzyme replace therapy but newer treatment options are in development, including treatments that may address the central symptoms. Supported by an educational grant from Takeda Pharmaceuticals U.S.A. Inc.

For complete activity information and to obtain CME credit, please go to https://checkrare.com/learning-center/courses/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

This accredited CME activity, led by Gregory Grabowski, MD, Professor Emeritus at University of Cincinnati College of Medicine highlights the latest research about Gaucher disease presented at WORLDSymposium 2022 provides expert analysis of its clinical relevance for busy members of the care team to help them care for patients they may encounter with this rare condition.

Gaucher disease is a genetic lysosomal storage disorder in which glucocerebroside accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen. Current therapies options include enzyme replace therapy or substrate reduction therapy but newer treatment options are in development. Furthermore, there is a genetic link between Gaucher disease and Parkinson’s disease that is currently being investigated.

Supported by an educational grant from Takeda Pharmaceuticals U.S.A. Inc.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

A group of leading experts in pediatric neurology and movement disorders attended a virtual roundtable to discuss diagnostic, symptomatic, and research aspects of aromatic L-amino acid decarboxylase (AADC) deficiency.

AADC deficiency is characterized by a defect in the dopa decarboxylase or DDC gene; this dysfunction leads to reduced production of the critical neurotransmitters dopamine, norepinephrine, epinephrine, and melatonin. As a result, patients with AADC deficiency can suffer deficits in vital motor function.

The symptoms of this very rare genetic disorder usually appear before children reach one year of age. Patients with severe symptoms rarely survive beyond age 10. Although patients with moderate symptoms can live into adulthood, those afflicted with AADC deficiency often experience developmental disability and can require lifelong care. The participants included:

Philip L. Pearl, MD
Director, Epilepsy and Clinical Neurophysiology, Boston Children’s Hospital
William G. Lennox Chair and Professor of Neurology, Harvard Medical School
Boston, MA

Warren A. Marks, MD
Medical Director, Movement Disorders
Cook Children’s Jane and John Justin Neurosciences Center
Fort Worth, TX

Paul Wuh-Liang Hwu, MD, PhD
Professor, Department of Pediatrics and Medical Genetics
National Taiwan University Hospital
Tapei, Taiwan

Irina A. Anselm, MD
Director of the Mitochondrial Program and Co-Director of the Neurometabolic Program, Boston Children’s Hospital
Assistant Professor of Neurology, Harvard Medical School
Boston, MA

Jennifer O’Malley, MD, PhD
Clinical Assistant Professor, Neurology & Neurological Sciences, Stanford Medicine
Pediatric Neurologist, Stanford Children’s Health
Stanford, CA

Moderated by Dr. Pearl, the roundtable participants described the first recognized case of AADC deficiency, and the fact that the prevalence and incidence of the condition is not yet clear. One problem is that the presentation of infants with AADC deficiency is not very specific, and a large number of patients are probably not yet diagnosed, said Dr. O’Malley. Unexplained hypotonia is a useful sign, she explained, which clinicians can use to go down the path to diagnosis. Dr. Marks commented that when children present with movement disorders at his center, he has a very low threshold to begin genetic testing for AADC deficiency, which will rapidly eliminate or confirm the diagnosis. Dr. Hwu emphasized that clinical recognition is the first step: Once you make one diagnosis, it isn’t too difficult to identify the second patient.

Symptomatic treatment can be useful, particularly in patients with milder forms of AADC deficiency, said Dr. Anselm. For example, similar to Parkinsonism, dopamine agonists can have positive results, but dyskinesias are problematic.

Gene therapy holds promise, according to Dr. Hwu, but he cautioned that even if successful, a good deal of movement training and patience will be required to gain movement control.

Drs. O’Malley and Anselm believe that collaboration and education among the different disciplines (e.g., child neurologists and physiatrists) is key to improving recognition of AADC deficiency and gaining early treatment.

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

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This accredited CME activity, led by Carlos De Castro, MD, Professor of Medicine, Duke Hematologic Malignancies Clinic, highlights the latest information about paroxysmal nocturnal hemoglobinuria (PNH) presented at ASH 2021 and provides expert analysis of its clinical relevance for busy members of the care team in order to help them care for patients they may encounter with this rare condition.

PNH is a rare, acquired blood disease characterized by hemolytic anemia, bone marrow failure, thrombosis, and fatigue.

Supported by an educational grant from Apellis.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Karuppiah Kannan, Senior Director - Global Program Leader at Takeda Pharmaceuticals, discusses early results of a phase 1/2 study evaluating subasumstat (TAK-981) in combination with rituximab in multiple subsets of CD20-positive relapsed/refractory non-Hodgkin lymphoma including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL) and marginal zone lymphoma (MZL). The results of this study were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

Subasumstat is an investigational, first-in-class small-molecule inhibitor of SUMOylation, which mediates cell cycle progression. In preclinical trials, subasumstat was shown to add synergistic benefit when combined with rituximab in non-Hodgkin lymphoma models.

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

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Jerry Vockley, MD, PhD, Head of the Division of Medical Genetics at UPMC Children’s Hospital of Pittsburgh, gives an update on the phase 2 trial testing SYNB1618 to treat phenylketonuria (PKU).

PKU is a rare genetic metabolic disorder that results in reduced activity of phenylalanine hydroxylase that leads to an accumulation of phenylalanine in the body, which can cause significant organ damage, especially in the central nervous system. If left untreated, PKU patients can develop chronic intellectual, neurodevelopmental, and psychiatric disabilities, as well as seizures and heart problems. Lifelong restriction of phenylalanine intake through the diet is needed to prevent buildup of phenylalanine in the body. However, compliance is an issue with this type of diet.

Interim data from the phase 2 SynPheny-1 clinical trial was recently presented at the International Congress of Inborn Errors of Metabolism (ICIEM) Meeting. These data show that treatment with SYNB1618, an investigational oral drug, resulted in significant reductions in plasma phenylalanine levels in patients with PKU.

In an interim analysis of eight patients, treatment with SYNB1618 was associated with a 40% reduction in D5-phenylalanine absorption after a meal challenge. Treatment with SYNB1618 was also associated with a 20% reduction in mean fasting plasma phenylalanine across all subjects.

According to Dr. Vockley, because patients tend to “behave themselves” when they know they will have their phenylalanine levels measured by a professional, patients in the study may have had lower-than-average plasma phenylalanine at baseline. Ultimately, this means that the 20% reduction seen in the interim analysis may be a smaller reduction than what would be seen in real-world settings and that treatment with SYNB1618 may actually lead to an even greater reduction in plasma phenylalanine. Finally, in the interim analysis, treatment with SYNB1618 was associated with >250 µM mean reduction in fasting plasma phenylalanine among responder subjects. Treatment with SYNB1618 was also generally well tolerated, with no serious adverse events and a tolerability profile consistent with results from previous Phase 1 studies.

To learn more about PKU and other rare metabolic disorders, visit checkrare.com/diseases/metabolic-disorders/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

This accredited CME activity, led by David Kronn, MD, Associate Professor of Pathology and Pediatrics at New York Medical College, is the fourth module in a four-part curriculum focused on Best Practices for Explaining Newborn Screening Results to Parents. This module will focus on hemoglobinopathies and newer disorders which are part of the Recommended Uniform Screening Panel (RUSP) in order to better prepare clinicians to discuss positive results with new parents.

Supported by an educational grant from bluebird bio Inc. and Ultragenyx Pharmaceutical Inc.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

This accredited CME activity, led by Jerry Vockley, MD, PhD, Chief of Genetic and Genomic Medicine at the University of Pittsburgh, is the third module in a four-part curriculum focused on Best Practices for Explaining Newborn Screening Results to Parents. This module will focus on metabolic diseases which are part of the Recommended Uniform Screening Panel (RUSP) in order to better prepare clinicians to discuss positive results with new parents.


Supported by an educational grant from bluebird bio Inc. and Ultragenyx Pharmaceutical Inc.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.