CheckRare Featured Podcasts

 

You can listen and subscribe to CheckRare podcasts from this site or from many of the popular podcast apps, including iTunes, Spotify, JioSaavan, Spreaker, CastBox, PodcastRepublic, Apple Podcasts, Amazon, Listen Notes, and other platforms.

 

This CME activity, hosted by Nicholas Silvestri, MD, of the University of Buffalo, provides an overview of the latest clinical research presented at AAN 2024 focused on myasthenia gravis. Treatment of myastheniagravis is highly individualized and depends greatly on the myasthenia gravis subtype of each patient as well as each patient’s comorbidities. There are currently five drugs approved by the FDA, eculizumab, efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan. Clinical trial data on these therapies, as well as real world data, were presented at the American Academy of Neurology Annual Meeting (AAN 2024) held in Denver, CO. Full program can be viewed here.

 

In this first part of our three-part series on Fabry disease, we feature William Burns, MD, a biochemical geneticist at Greenwood Genetic Center in Greenwood, South Carolina. Dr. Burns summarizes this rare disease, including current management strategies.

 

In this second of our three-part series focusing on Fabry disease, we talk with Nicola Longo, MD, Chief of the Division of Medical Genetics at the University of Utah, Spencer Fox Eccles School of Medicine in Salt Lake City. Dr. Longo discusses Fabry disease, including the progression of the disease and personalized medicine.

 

In this final episode of our series focused on Fabry disease, we feature Maya Kineen, a patient and advocate with this rare disorder.

 

Ozlem Goker-Alpan, MD, Founder and President, LDRTC and David G. Warnock, MD. Professor of Medicine (Emeritus) at University of Alabama at Birmingham discuss best practices to identify and treat kidney problems associated with lysosomal disorders. To receive credit for this program, go to https://checkrare.com/learning/

 

Ozlem Goker-Alpan, MD of LDRTC and John Bach, MD, Professor of Neurology at Rutgers School of Medicine discuss best practices to manage respiratory complications in persons with lysosomal disorders. To receive credit for this program, visit https://checkrare.com/learning/p-ldrtc2023-webinar3-assessing-monitoring-managing-respiratory-involvement-in-lysosomal-disorders/

 

This 40-minute CME-accredited program, hosted by Aleena Banerji, MD, Associate Professor at Harvard Medical School and Clinical Director of the Massachusetts General Hospital ( MGH) Allergy and Immunology Unit, highlights the current and future treatment options for patients with hereditary angioedema (HAE).  To obtain CME credit, go to https://checkrare.com/learning/p-hereditary-angioedema-current-and-future-treatment-options/

 

In this final episode of our four-part series focused on alpha-mannosidosis, we feature Rhonda Skipper, a mom of two boys, Dale and Matt, who have this rare disease.

 

This is the third of a four-part series focusing on alpha-mannosidosis. In this episode, we feature Dr. Markey McNutt, who will focus on the challenges of identifying and caring for patients with this rare disease. Dr. McNutt is a Clinical Geneticist at the University of Texas Southwestern Medical Center in Dallas.

 

This is the second of a four-part series focusing on alpha-mannosidosis. In this episode, we talk with Dr. Reid Sutton on the challenges of recognizing this rare disease, focusing on the signs and symptoms. Dr. Sutton is a Clinical Geneticist and a Clinical Biochemical Geneticist at Baylor College of Medicine and Texas Children’s Hospital in Houston.

 

In this first part of our four-part series on alpha-mannosidosis, we feature Laura Buch, a physician assistant who practices medical genetics at the Greenwood Genetic Center in South Carolina. Laura’s work focuses on the diagnosis and treatment of patients with abnormal newborn screens, inborn errors of metabolism, and lysosomal storage disorders. She also cares for alpha-mannosidosis patients.

 

This 45-minute CME-accredited program, hosted by James F Howard Jr, MD, Professor of Neurology, Medicine & Allied Health at The University of North Carolina at Chapel Hill, highlights the connection between the complement system and myasthenia gravis in regards to the pathophysiology and treatment of this rare disease.

 

Activity Faculty Aliya Khan MD, FRCPC, FACP, FACE, FASBMR Clinical Professor of Medicine Director, Calcium Disorders Clinic Director, Fellowship in Metabolic Bone Disease McMaster University

Learning Objectives: After participating in the activity, learners should be better able to • Describe the latest recommendations for diagnosing patients with TIO• Describe the latest recommendations for treating patients with TIO. To earn credit, go to https://checkrare.com/learning/p-new-guidance-to-diagnose-and-treat-tumor-induced-osteomalacia-tio-2023-1/

 

This 30-min CME program provides an overview of the latest clinical research presented at ENDO 2023 involving Cushing’s disease.

Faculty Lisa Nachtigall, MD, Clinical Director, Neuroendocrine & Pituitary Tumor Clinical Center, Massachusetts General Hospital; Associate Professor of Medicine, Harvard Medical School

To obtain CME credit, go to https://checkrare.com/learning/p-cushings-disease-research-highlights-endo-2023/

 

Raymond Douglas, MD, PhD, a world-leading clinician and thought leader in thyroid eye disease (TED) who has been integral to developing therapeutics for the disease, provides an overview of TED, including diagnosis challenges and current and emerging treatments for this rare disease.

TED is a rare autoimmune disease that can dramatically impact a person’s vision. The condition often occurs in people with hyperthyroidism or Graves’ disease. Common symptoms can include upper eyelid retraction, dry eyes, inflammation, light sensitivity, as well as the sensation of a foreign body present in the eye.

 

Wenyu Huang, MD, PhD Associate Professor Northwestern University Feinberg School of Medicine Chicago, hosts this 30-minute CME program on the latest clinical research about acromegaly, a rare, endocrine disorder. 

To earn a CME credit, go to https://checkrare.com/learning/p-acromegaly-research-highlights-endo-2023/

 

This CME/CE activity, hosted by Ozlem Goker-Alpan, MD and John Jefferies, MD, describes the pathophysiologies and management options for lysosomal disease patients with cardiomyopathies. This continuing education activity is provided through collaboration between the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), CheckRare CE, and AffinityCE. This activity provides continuing education credit for physicians, physician assistants, nurses, nurse practitioners, and genetic counselors. A statement of participation is available to other attendees. 

To receive credit for this program, go to https://checkrare.com/learning/p-ldrtc2022-webinar2-managing-cardiomyopathies-in-lysosomal-disorders/  

 

 

This 30-minute CME program hosted by Vera Bril, MD, of the University Hospital Network in Toronto, Canada, provides an overview of the latest clinical research presented at AAN 2023 focused on myasthenia gravis. 

Treatment of myasthenia gravis is highly individualized and depends greatly on the myasthenia gravis subtype of each patient as well as each patient’s comorbidities. There are currently four drugs approved by the FDA, eculizumab, efgartigimod, ravulizumab, and rozanolixizumab. There are also treatments in development. Clinical trial data on these therapies were presented at the American Academy of Neurology Annual Meeting (AAN 2023) held in Boston, MA. 

Supported by educational grants from argenx US, Inc. and UCB Inc. For complete activity information and to obtain CME credit, please, go to https://checkrare.com/learning/p-myasthenia-gravis-research-highlights-aan-2023/ 

This continuing education activity is provided through collaboration between the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), CheckRare CE, and AffinityCE. This activity provides continuing education credit for physicians, physician assistants, nurses, nurse practitioners, and genetic counselors. A statement of participation is available to other attendees. 

Speakers: Ozlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and  Al-Hertani, MD, Director of the BCH Metabolism and Lysosomal Programs Boston Children’s Hospital; Associate Professor of Pediatrics, Harvard Medical School

Support for this educational activity was provided by Takeda, Sanofi, Amicus Therapeutics and Chiesi USA.

To earn credit for this CME, go to https://checkrare.com/learning/p-building-and-maintaining-a-multidisciplinary-team-for-lysosomal-disorders/ 

Sindhu Ramchandren, MD, Global Clinical Leader at Janssen Pharmaceuticals, explains the pathophysiology of myasthenia gravis and the need for more targeted therapies.

Myasthenia gravis is an autoimmune, neuromuscular disorder 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 presence of antibodies against acetylcholine receptors in the neuromuscular junction usually causes the condition.

 

This CME program, hosted by Staci Kallish, DO, Associate Professor of Clinical Medicine at the University of Pennsylvania Health System Penn Medicine,  provides an overview of the latest clinical research presented at WORLDSymposium 2023 focused on Fabry disease. To watch the video and obtain CME credit, go to https://checkrare.com/learning-center/courses/ 

This 30-minute CME program highlights the latest clinical research about Fabry disease, is a rare X-linked lysosomal disorder that results in the cellular buildup of globotriaosylceramide. Characteristic features of Fabry disease include acroparesthesias, angiokeratomas, hypohidrosis, corneal opacity, gastrointestinal problems, tinnitus, and hearing loss. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke.

 

Warm autoimmune hemolytic anemia (wAIHA) is the most common type (60-70%) of autoimmune hemolytic anemia (AIHA). In most cases, wAIHA is due an immunoglobulin G (IgG) autoantibody that binds to red blood cells (RBC), leading to hemolysis. Current recommendations for managing people with wAIHA are largely based on case series and retrospective studies involving off-label medications. Also, while there are currently no medications specifically approved to treat wAIHA, data are emerging on new therapies under investigation which may impact treatment in the future. 

This 60-minute CME program, hosted by Irina Murakhovskaya, MD, of the Montefiore Medical Center, Albert Einstein College of Medicine, in New York, NY and Bruno Fattizzo, MD, of the University of Milan and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, in Milan, Italy, describes current best practices to manage patients with wAIHA.

 

Dr. Harrison Farber, a pulmonologist and director of the Pulmonary Embolism Response Team at Tufts Medical Center discusses a chronic rare disease that affects the circulatory system in the lungs and directly affects the ability of the lungs to function.

Pulmonary Arterial Hypertension, or PAH, is characterized by shortness of breath, dizziness, and chest pressure. Dr. Harrison Farber joins us to discuss the impact of COVID-19 on PAH patient care.

 

This CME/CE activity, hosted by Ozlem Goker-Alpan, MD, Co-founder and President Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and guest lecturer, Oral Alpan, MD, of Amerimmune in McLean, VA, provides an overview of our current understanding of the immune system in the pathophysiology and management of lysosomal disorders. At the end of this activity, participants should be able to:

• Describe how the immune system is involved in Lysosomal Storage Disorders.
• Review the pathophysiology of immune response reactions.
• Describe how to better manage patients with immune response reactions.
• Describe the best clinical practices to monitor the patients with immune response reactions.

 

 

Guillaume Canaud, MD, PhD, of the Paris Descartes University, explains why it is important to regularly measure objective outcomes in persons with PiK3CA-related overgrowth syndrome (PROS).

PROS is a group of rare congenital disorders that lead to the overgrowth of parts of the body. PROS is caused by gain of function mutations in the PIK3CA gene. Specific disorders under the umbrella of PROS include fibroadipose hyperplasia, hemihyperplasia multiple lipomatosis (HHML), CLOVES syndrome, macrodactyly, fibroadipose infiltrating lipomatosis, megalencephaly-capillary malformation (MCAP), and dysplastic megalencephaly (DMEG).

 

 

Sean J. Pittock, MD, Director of Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology and of Mayo’s Neuroimmunology Laboratory discusses the latest results from Phase III CHAMPION-NMOSD trial recently presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress. The results showed that treatment with ravulizumab-cwvz significantly reduced relapse risk in adults with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD).

NMOSD is a rare central nervous disorder that primarily affects the spinal cord and optic nerves. Symptoms of NMOSD may include blindness in one or both eyes, weakness or paralysis of arms or legs, spasming, loss of sensation, uncontrollable vomiting and hiccups, and bladder/bowel problems due to spinal cord damage. Relapse is very common in persons with  NMOSD and episodes can be severe enough to cause permanent disability.  

 

Angela Scheuerle, MD, Medical Geneticist at the UT Southwestern Medical Center, discusses National Organization for Rare Disorders’ (NORD) Rare Disease Centers of Excellence of which UT Southwestern is one.

There are currently 31 NORD Rare Disease Centers of Excellence across the United States. The primary goal for establishing this network was to advance care and expand access for rare disease patients. The second goal was to enable rare disease experts to work collaboratively, which will hopefully lead to faster progress in terms of diagnoses, treatments, and development of guidelines and new therapies. 

 

This CME/CE activity, hosted by Ozlem Goker-Alpan, MD, Co-founder and President Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and Sonata Jodele, MD, Research Professor of Pediatrics at Cincinnati Children’s Hospital Medical Center, highlights the current trends in gene therapy for lysosomal storage diseases as well as some of the safety concerns with such therapy. At the end of this activity, participants should be able to: 

• Describe the limitations and unmet needs of the current therapeutic landscape for lysosomal disorders 
• Review the gene transfer therapies for lysosomal disorders 
• Describe the best clinical practices to monitor the safety profile of gene therapy 
• Describe the best practices for gene therapies 

Educational Support for this activity was provided by Takeda, Sanofi, and Chiesi. To obtain CME credit, please visit https://checkrare.com/learning-center/courses/

 

This CME/CE activity, hosted by Ozlem Goker-Alpan, MD, Co-founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and Neal J Weinreb, MD, FACP, Voluntary Associate Professor of Human Genetics, University of Miami Miller School of Medicine, highlights how enzyme replacement therapies (ERTs) and substrate reduction therapies (SRTs) for lysosomal storage disorders have transformed, and will continue to transform, the treatment landscape for these rare conditions. 

At the end of this activity, participants should be able to:
• Describe how ERTs/SRTs have transformed the LSD population
• Describe the new research underway to improve safety and efficacy of ERTs/SRTs
• Describe how ERTs/SRTs are addressing the problem of the blood brain barrier

Educational Support for this activity was provided by Takeda, Sanofi, and Cheisi. To obtain CME credit, please visit https://checkrare.com/learning-center/courses/

 

This 30-minute CME program highlights best practices to diagnose Cushing’s disease and to manage the comorbidities commonly observed in  persons with this rare disorder. Cushing’s disease is caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor.  Optimal patient outcomes require an accurate diagnosis, proper selection of individualized treatment, and good management of the disease and its associated comorbidities.

The program features two experts, Beverly Biller, MD, Professor of Medicine at Harvard Medical School and Maria Fleseriu, MD, Professor of Medicine and Neurological Surgery at Oregon Health and Science University, who were actively involved in the recently published consensus on the diagnosis and management of Cushing’s diseases in Lancet Diabetes Endocrinology.

Supported by an educational grant from  Xeris Pharmaceuticals, Inc. To obtain credit, visit checkrare.com/learning-center/courses/ 

 

This 30-minute CME program highlights new treatment options that are available for persons with  Cushing’s disease. 

Cushing’s disease is caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor.  Optimal patient outcomes require an accurate diagnosis, proper selection of individualized treatment, and good management of the disease and its associated comorbidities.

The program features two experts, Maria Fleseriu, MD, Professor of Medicine and Neurological Surgery at Oregon Health and Science University and  Beverly Biller, MD, Professor of Medicine at Harvard Medical School, who were actively involved in the recently published consensus on the diagnosis and management of Cushing’s diseases in Lancet Diabetes Endocrinology.

Supported by an educational grant from  Xeris Pharmaceuticals, Inc. To obtain credit, visit checkrare.com/learning-center/courses/ 

Barry S. Ticho, MD, PhD, Chief Medical Officer at Stoke Therapeutics, gives a detailed overview of Dravet syndrome.

As Dr. Ticho explains, Dravet syndrome is a rare neurological condition that usually appears during the first year of life as frequent febrile seizures. As the condition progresses, other types of seizures typically occur, including myoclonus and status epilepticus. Moderate to severe cognitive impairment is also common. Most cases of Dravet syndrome occur due to a mutation of the SCN1A gene. The SCN1A gene codes for the protein NaV1.1. With only one functional SCN1A gene, people with Dravet syndrome produce less of the NaV1.1 protein. NaV1.1 is an important protein for the nerves in the brain to work properly. Low levels of NaV1.1 in the brain can lead to seizures and other symptoms of Dravet syndrome.

 

Larry J Bauer, Senior Regulatory Drug Expert from Hyman, Phelps, & McNamara PC, a dedicated food and drug law firm, discusses the history and purposes of patient-focused drug development (PFDD) meetings. As Mr. Bauer explains, PFDD meetings  are designed to engage patients and learn their perspectives on the most significant symptoms of their condition and the impact of the condition on daily life, as well as their current approaches to treatment. 

In 2012, the U.S. Food and Drug Administration (FDA) initiated PFDD meetings to more systematically obtain patient perspectives on diseases, both rare and non-rare, as well as their currently available treatments. Furthermore, PFDD meetings provide the FDA and other key stakeholders an opportunity to hear from patients, their families, caregivers, and patient advocates directly about the symptoms that matter most to them, the impact of disease on daily life, and patients’ experiences with currently available treatments.

 

Michael L. Wang, MD, Professor, Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center, discusses results of the phase 3 SHINE study which evaluated the safety and efficacy of ibrutinib in combination with bendamustine and rituximab in patients 65 years of age or older with newly diagnosed mantle cell lymphoma. These data were recently presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting and were published in The New England Journal of Medicine.

Mantle cell lymphoma is a rare form of non-Hodgkin’s lymphoma in which B-cells become cancerous and form tumors in the lymph nodes that can quickly spread to other regions. It commonly affects people over the age of 65 who typically cannot tolerate intensive chemoimmunotherapy and stem cell transplantation, resulting in poor clinical outcomes.

 

Axel Bolte, MSc, MBA, Co-Founder, President, and Chief Executive Officer, Inozyme Pharmaceuticals, gives an overview of ENPP1 deficiency.

The ENPP1 gene produces a critical enzyme called ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1), which regulates inorganic pyrophosphate (PPi) levels in plasma. PPi is essential for preventing harmful soft tissue calcification and for regulating normal bone mineralization. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI), which is characterized by extensive vascular calcification and neointimal proliferation, resulting in myocardial infarction, stroke, or cardiac or multiorgan failure. 

 

This accredited CME activity, led by Satheesh Chonat, MD, Assistant Professor at Emory University School of Medicine and hematologist-oncologist at the Pediatric Hematology Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, highlights the latest real world data focused on paroxysmal nocturnal hemoglobinuria (PNH). Dr Chonat also provides expert analysis of the data’s clinical relevance for members of the care team to help them manage patients with PNH 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 Alexion Pharmaceuticals, Inc. 

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

Damian M. May, PharmD, MBA, Senior Director Of Health Economics and Outcomes Research at Acadia Pharmaceuticals, discusses data on the patient journey and clinical burden of Rett syndrome in the United States. This data was presented at the 2022 AAN Annual Meeting.

​​Rett syndrome is a rare progressive neurodevelopmental condition that primarily affects girls. These girls appear to have normal psychomotor development during the first 6 to 18 months of life, followed by a developmental “plateau,” and then rapid regression in language and motor skills. Common symptoms include hand-wringing; fits of screaming and inconsolable crying; autistic features; panic-like attacks; bruxism; episodic apnea and/or hyperpnea; gait ataxia and apraxia; tremors; seizures; and slowed head growth. Rett syndrome is most commonly caused by a sporadic mutation in the MECP2 gene on the X chromosome. The majority of cases are not inherited from a parent.

 

Ozlem Goker-Alpan, MD, Founder and Chief Medical Officer at Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and discusses the latest develops in biomarker research and how biomarkers can improve how patients with lysosomal disorders, such as Gaucher disease and Fabry disease, are managed. 

To obtain CME/CE credit for this program, go to www.checkrare.com Support for this educational activity was provided by Takeda, Sanofi and Chiesi.

This accredited CME activity, led by Paula Busse, MD, Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai, provides a summary of the latest information about hereditary angioedema (HAE) that was presented at the American Academy of Allergy, Asthma, & immunology 2022 (2022 AAAAI) Annual Meeting. Since to the Covid-19 pandemic limited the ability for AAAAI members to commit fully to the 4-day event, this program provides a concise means to share the clinically relevant information presented at this meeting with AAAAI members as well as other health care professionals who manage individuals with HAE. 

Supported by an educational grant from CSL Behring. For complete activity information and to obtain CME credit, please go to https://checkrare.com/learning-center/courses/

 

 

Raymond Wang, MD, Metabolic Specialist and Director of the Multidisciplinary Lysosomal Storage Disorder Program at Children’s Hospital of Orange County, provides an extensive overview of mucopolysaccharidosis type I (MPS I), also known as Hurler syndrome. In this interview, Dr. Wang explains this rare condition, including its pathophysiology, prevalence, and natural progression. He also discusses the current treatment options for MPS I as well as the work he is doing to assess the safety and efficacy of gene therapy (RGX-111) for this rare disease.  

MPS I is an inherited lysosomal storage disorder caused by a deficiency in the enzyme, alpha-L-iduronidase, which is responsible for breaking down glycosaminoglycans (GAGs). In moderate to severe forms of the disease, the accumulation  of GAGs in the central nervous system leads to hydrocephalus, spinal cord compression, and cognitive impairment. Additional symptoms may include clouded corneas; enlarged liver, spleen, and heart; noisy breathing; recurring upper respiratory tract; ear infections; difficulty swallowing; and periodic bowel problems. 

 

 

Steve Pakola, MD, Chief Medical Officer for Regenxbio, discusses data from the ongoing gene therapy trials in children with mucopolysaccharidosis type I (MPS I) and mucopolysaccharidosis type II (MPS II). Positive Data from Regenxbio’s Gene Therapy Trials for MPS I and MPS IIThe data was presented at WORLDSymposium 2022.

MPS I is an inherited lysosomal storage disorder caused by a deficiency in the enzyme, alpha-L-iduronidase, which is responsible for breaking down glycosaminoglycans (GAGs). These GAGs accumulate in the tissues of MPS I patients, resulting in a diverse clinical profile. In moderate to severe forms of the disease, this accumulation in the central nervous system leads to hydrocephalus, spinal cord compression, and cognitive impairment. Additional symptoms may include clouded corneas; enlarged liver, spleen, and heart; noisy breathing; recurring upper respiratory tract; ear infections; difficulty swallowing; and periodic bowel problems. 

MPS II 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). This disease has a variable clinical presentation but common signs and symptoms include: developmental decline between 18 and 36 months, followed by progressive loss of skills; coarse facial features; skeletal irregularities; obstructive airway and respiratory complications; joint stiffness; retinal degeneration; and communicating hydrocephalus.

 

 

Juan Roman, Vice President at Krystal Biotech, gives an overview of dystrophic epidermolysis bullosa (DEB).

As Mr. Roman explains, DEB is one of the major forms of epidermolysis bullosa, a group of genetic skin diseases that cause the skin to blister and erode very easily. The signs and symptoms of DEB vary widely among affected people. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases often involve widespread blistering that can lead to vision loss, disfigurement, and other serious medical problems. DEB is caused by mutations in the COL7A1 gene and may be inherited in an autosomal dominant or autosomal recessive manner depending on the subtype. Some patients need nutritional support, supplements, occupational therapy and/or surgery depending on the associated features of the disease. Currently, there are no approved targeted treatments for DEB, but Krystal Biotech announced positive topline results in November 2021 from the phase 3 GEM-3 study using redosable gene therapy, beremagene geperpavec (Vyjuvek), in DEB patients.

 

 

Edward Neilan, MD, PhD, Chief Scientific and Medical Officer at the National Organization for Rare Disorders (NORD), discusses the organization’s recently established Rare Disease Centers of Excellence.

As Dr. Neilan explains, there were two main goals when establishing a national network of rare disease centers. The first goal was to help rare disease patients find medical centers that have deep and broad expertise and could assist them with their diagnosis or treatment of their disease. The second goal was to enable rare disease experts to work collaboratively, which will hopefully lead to faster progress in terms of diagnoses, treatments, and development of guidelines and new therapies.  

 

 

Steven Pipe, MD, Professor of Pediatrics and Pathology, and Pediatric Medical Director of the Hemophilia and Coagulation Disorders Program at the University of Michigan, discusses the recent announcement of positive long-term results from the phase 3 HOPE-B clinical trial evaluating etranacogene dezaparvovec (EtranaDez), an investigational gene therapy for hemophilia B.

Hemophilia B is a congenital bleeding disorder due to dysfunction or deficiency of coagulation Factor IX (FIX). People with this condition may bleed for longer periods of time after injury or surgery. They are also susceptible to spontaneous bleeding in muscles, joints and organs, which can be extremely painful and, in some cases, life-threatening. Etranacogene dezaparvovec is an investigational adeno-associated virus five (AAV5)-based gene therapy for people living with hemophilia B. 

 

 

Jeffrey L. Neul, MD, PhD, Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education at Vanderbilt University Medical Center, gives an overview of Rett syndrome.

As Dr. Neul explains, ​​Rett syndrome is a rare progressive neurodevelopmental condition that primarily affects girls. These girls appear to have normal psychomotor development during the first 6 to 18 months of life, followed by a developmental “plateau,” and then rapid regression in language and motor skills. Common symptoms include hand-wringing; fits of screaming and inconsolable crying; autistic features; panic-like attacks; bruxism; episodic apnea and/or hyperpnea; gait ataxia and apraxia; tremors; seizures; and slowed head growth. 

 

 

Raymond Wang, MD, Metabolic Specialist and Director of the Multidisciplinary Lysosomal Storage Disorder Program at Children’s Hospital of Orange County, discusses RGX-111, an investigational gene therapy for mucopolysaccharidosis type I (MPS I). 

MPS I is an inherited lysosomal storage disorder caused by a deficiency in the enzyme, alpha-L-iduronidase, which is responsible for breaking down glycosaminoglycans (GAGs). In moderate to severe forms of the disease, the accumulation  of GAGs in the central nervous system leads to hydrocephalus, spinal cord compression, and cognitive impairment. 

 

 

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.

 

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.

 

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. 

 

Jeffrey A. Zonder, MD, Hematologist-Oncologist from the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, describes the treatment landscape for patients with relapsed or refractory multiple myeloma.

Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. Abnormal plasma cells – also known as myeloma cells – interfere with the production of healthy blood cells in the bone marrow. Myeloma cells also produce inactive clones of abnormal antibodies that may negatively affect the bones and kidneys. Symptoms of multiple myeloma may include: bone pain (particularly in the chest and spine), frequent infections, weakness or numbness in the legs, fatigue, confusion, excessive thirst, and constipation. While the disease is treatable, relapses are common and some patients are refractory to first line therapy.

 

Phillip Moreau, MD, PhD, Head of the Hematology Department at the University Hospital Hôtel-Dieu, discusses the updated results from MajesTEC-1, a phase 1/2 study of teclistamab in relapsed/refractory multiple myeloma. These results were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

Multiple myeloma is a rare blood cancer. While the disease is treatable, relapses are common and some patients are refractory to first line treatment. As Dr. Moreau explains, MajesTEC-1 is a phase 1/2 study testing teclistamab in relapsed/refractory multiple myeloma. Teclistamab is a T-cell redirecting, bispecific IgG4 antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell mediated cytotoxicity of BCMA-expressing myeloma cells. In this study, two cohorts were evaluated, one cohort given teclistamab weekly and one biweekly. Updated data on both of these cohorts was presented at the ASH 2021 meeting. 

 

Paolo Ghia, MD, PhD, Professor at the Università Vita-Salute San Raffaele, Milan, Italy, discusses the updated, long-term data from the phase 2 CAPTIVATE study. This study evaluated ibrutinib plus venetoclax as a first-line treatment for chronic lymphocytic leukemia (CLL); data from this trial was presented at the American Society of Hematology Meeting & Exposition (ASH 2021).

 

Jeffrey Neul, MD, PhD, Professor of Pediatrics at Vanderbilt University Medical Center, discusses recent top-line results from a phase 3 trial testing trofinetide to treat children with Rett syndrome. Trofinetide is an analog of insulin-like growth factor 1 (IGF-1) and it is speculated that the orphan drug can restore homeostasis of neuronal signaling in diseases such as Rett syndrome.

​​Rett syndrome is a rare progressive neurodevelopmental condition that primarily affects girls. These girls appear to have normal psychomotor development during the first 6 to 18 months of life, followed by a developmental “plateau,” and then rapid regression in language and motor skills. Common symptoms include hand-wringing; fits of screaming and inconsolable crying; autistic features; panic-like attacks; bruxism; episodic apnea and/or hyperpnea; gait ataxia and apraxia; tremors; seizures; and slowed head growth. Rett syndrome is most commonly caused by a sporadic mutation in the MECP2 gene on the X chromosome. The majority of cases are not inherited from a parent. 

 

Jeffrey A. Zonder, MD, hematologist-oncologist at the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, discusses data from the first-in-human study testing REGN5458 as a monotherapy for relapsed/refractory multiple myeloma patients (NCT03761108). Data from the phase 1 portion of this study were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.

As Dr. Zonder explains, REGN5458 is a BCMA x CD3 bispecific antibody that is currently being investigated in a phase 1/2 clinical trial. Data presented at ASH 2021 was related to the phase 1 portion of this study which is assessing the safety, tolerability, and dose-limiting toxicities (DLTs) of REGN5458 in patients with relapsed/refractory multiple myeloma as well as determining a recommended phase 2 dose regimen.

 

Arnon Kater, MD, PhD, Professor of Internal Medicine in the Faculty of Medicine at the University of Amsterdam discusses new data from the GLOW study of ibrutinib plus venetoclax (I+V) in elderly or unfit chronic lymphocytic leukemia (CLL) patients. The data were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021). CLL is a rare blood cancer resulting in a build-up of lymphocytes in bone marrow, lymph nodes, and blood. The disease is considered treatable, but relapse is very common. Furthermore, many CLL patients cannot withstand the intensive chemotherapy needed to bring them into complete remission.

 

Anne Pariser, MD, Director of the NCATS’ Office of Rare Diseases Research (ORDR), provides an overview of the ORDR and the research they are involved with. The ORDR is focused on multiple programs to improve the efficacy of rare disease research. Their two largest programs are the Rare Diseases Clinical Research Network (RDCRN) and the Genetic and Rare Diseases Information Center (GARD). RDCRN provides support for clinical studies and facilitates collaboration, study enrollment and data sharing. Through the RDCRN consortia, researchers work with patient advocacy groups to study over 200 rare diseases at sites across the nation. GARD provides the public with up-to-date health information on many rare diseases. It has a hotline that people (often parents) can call and ask questions about a particular rare disease. To listen to more interviews with leaders in the rare disease community, sign up for our newsletter at checkrare.com/sign-up-for-our-newsletter/

 

Alan Mendelsohn, MD, Chief Medical Officer at Timber Pharmaceuticals, gives an update on their congenital ichthyosis clinical trial. Congenital ichthyosis is a rare genetic skin disorder characterized by dry, thickened, and scaling skin. Individuals with this condition may experience limited range in motion, chronic itching, an inability to sweat, and increased risk of infections. Currently, there is no approved targeted therapy for congenital ichthyosis. Symptom management for the condition is most often achieved with topical treatments (e.g., emollients, keratolytics, frequent baths, pumice stones) aimed at reducing the scaling and/or improving skin lubrication.

 

Avanish Vellanki, Cofounder and CEO at Rain Therapeutics, discusses the role of p53 and MDM2 in cancers like liposarcoma, the mechanism of action of milademetan, and the positive pre-clinical data presented at the 2021 World Conference of Lung Cancer.

 

Daniel Lovell, MD, MPH, Associate Director of the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center, provides an overview of juvenile idiopathic arthritis (JIA).

 

Daniel Auclair, MD, Chief Scientific Officer of the Multiple Myeloma Research Foundation (MMRF), discusses the foundation’s history and what they are currently doing to progress multiple myeloma research.

 

Tim Miller, PhD, CEO, President, and Co-Founder of Forge Biologics, discusses the phase 1/2 RESKUE study which will evaluate FBX-101 for the treatment of Krabbe disease. This clinical trial is currently recruiting. https://checkrare.com/gene-therapy-clinical-trial-for-krabbe-disease-is-recruiting-patients/

 

Tim Miller, PhD, CEO, President, and Co-Founder of Forge Biologics, gives an overview of Krabbe disease. https://checkrare.com/what-is-krabbe-disease/

 

William D. Tap, MD, Chief of the Sarcoma Medical Oncology Service at Memorial Sloan Kettering Cancer Center, gives an overview of tenosynovial giant cell tumors (TGCT), their symptoms, and why a multidisciplinary team is needed to treat them. https://checkrare.com/tgct-signs-and-symptoms-can-dictate-treatment-options/

 

Maria Fleseriu, MD, FACE, Professor of Medicine and Neurological Surgery and Director of the Pituitary Center at Oregon Health and Science University provides an overview of acromegaly research highlights presented at ENDO 2021. This CME activity is possible through an educational grant from Ipsen BioPharmaceuticals, Inc. To obtain credit for this activity, please visit https://checkrare.com/learning/p-acromegaly-highlights-from-endo-2021/

 

Please join Drs. Ozlem Goker-Alpan and Ari Zimran as they discuss the latest developments in the treatments for lysosomal storage diseases. To obtain credit for this activity, please visit https://checkrare.com/learning/p-lsd-webinar-series-current-and-emerging-therapies-for-lysosomal-storage-disease/

 

Anne Pariser, MD, Director of the NCATS’ Office of Rare Diseases Research (ORDR), provides an overview of the ORDR and the research they are involved with. The ORDR is focused on multiple programs to improve the efficacy of rare disease research. Their two largest programs are the Rare Diseases Clinical Research Network (RDCRN) and the Genetic and Rare Diseases Information Center (GARD). RDCRN provides support for clinical studies and facilitates collaboration, study enrollment and data sharing. Through the RDCRN consortia, researchers work with patient advocacy groups to study over 200 rare diseases at sites across the nation. To listen to more interviews with leaders in the rare disease community, sign up for our newsletter at checkrare.com/sign-up-for-our-newsletter/

 

Barbara K. Burton, MD from the Northwestern University Feinberg School of Medicine
Chicago, IL provides an overview of Mucopolysaccharidoses (MPSs) Highlights from WORLDSymposium. This CME activity is possible through an educational grant from Ultragenyx Pharmaceutical Inc. To obtain credit for this activity, please visit https://checkrare.com/learning/p-2020world-mps-highlights-from-worldsymposium-2020/

 

Morie A Gertz, MD, MACP, Professor of Medicine at the Mayo Clinic College of Medicine and Science in Rochester, Minnesota discusses best practices to diagnose ATTR amyloidosis. This CME activity is possible through an educational grants from Akcea Therapeutics and Alnylam Pharmaceuticals. To obtain credit for this activity, please visit https://checkrare.com/learning/p-managing-attr-module2-diagnosing-attr-amyloidosis/

 

Nancy L. Kuntz, MD, FAAN, Professor of Pediatrics and Neurology at Northwestern University Feinberg School of Medicine provides an overview of best practices to diagnose spinal muscular atrophy (SMA).  This CME activity is possible through an educational grant from AveXis. To obtain credit for this activity, please visit https://checkrare.com/learning/p-spinal-muscular-atrophy-module1-diagnosing-sma/

 

Edward M Wolin, MD, Professor of Medicine from the Icahn School of Medicine at Mount Sinai provides an overview of neuroendocrine tumors research highlights presented at ENDO 2020. This CME activity is possible through an educational grant from Ipsen BioPharmaceuticals, Inc. To obtain credit for this activity, please visit https://checkrare.com/learning/p-endo2020-neuroendocrine-tumors-nets-abstract-highlights/ 

 

Judy Shizuru, MD, Blood and Marrow Transplant Specialist, Stanford University School of Medicine, discusses clinical data from an ongoing phase 1 trial of JSP191 in patients with severe combined immune deficiency (SCID).

SCID is a group of inherited immune system disorders characterized by abnormalities with responses of both T cells and B cells. Common symptoms include an increased susceptibility to infections including ear infections; pneumonia or bronchitis; oral thrush; and diarrhea.
As Dr. Shizuru explains, JSP191 is a humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow.

 

Paul Orchard, MD from the University of Minnesota Medical School discusses Mucopolysaccharidosis I (MPS I) in this four-part CME/CE series. Without treatment, the prognosis for individuals with Mucopolysaccharidosis I (MPS I), especially the more severe form of the disease, is discouraging. Early access to treatment is also important in order to reduce disease damage and progression. In this module, our faculty educator will explore strategies for treating MPS I.

 

Recently, the US Food and Drug Administration (FDA) provided clearance to proceed with a Phase 2 clinical trial assessing HST5040 to treat children with propionic acidemia and methylmalonic acidemia, two rare inborn error of metabolism conditions that currently have limited treatment options. We talked with one of the principal investigators of the study, Marshall Summar, MD, Division Chief, Genetics and Metabolism and Director of the Rare Disease Institute at Children’s National Hospital.

 

Cyndi Frank, of the Gaucher Community Alliance explains her long diagnostic journey.

 

 

David Dale, MD at the University of Washington Medical Center in Seattle, discusses some of the challenges in diagnosing WHIM syndrome.

Individuals with WHIM syndrome have severe congenital neutropenia. In addition, because they also have profound white blood cell (WBS) deficiencies characterized as panleukopenia, WHIM syndrome is also classified as a severe combined immunodeficiency. B lymphopenia is particularly severe, and this probably accounts in part for hypogammaglobulinemia. Somepatients also have developmental defects of the cardiovascular, urogenital, and nervous systems, although only the cardiovascular defects appear to be clinically significant.

The first symptoms that appear in very young patients are recurrent bacterial infections (especially respiratory infections like sinusitis, otitis media, and pneumonia) and cellulitis. Another challenge to diagnosis is the transient normalization of white blood cells during acute infections, which is the moment when patients most commonly seek medical attention. This can lead clinicians into missing the key sign of low neutrophils. As a result, diagnosis is often delayed until other characteristics of WHIM appear, and delayed diagnosis challenges the initiation of appropriate treatment.

For more information on WHIM syndrome, visit the WHIM Syndrome Learning Center.

 

 

Heather Lau, MD, Director, Lysosomal Storage Disease Program at NYU Langone Health, provides an overview of how to manage a person with Gaucher disease during the current COVID-19 pandemic.

Gaucher disease is a genetic 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.

Many Gaucher disease symptoms, comorbidities, and treatment options can complicate how these patients are managed during the current pandemic. In this webinar, Dr. Lau explains the:

• Multisystemic manifestations of COVID-19
• Impact of COVID-19 on Gaucher
• Impact of COVID-19 on access to therapy
• Exposure to COVID-19. What to do?
• Ethical considerations of COVID-19 in Gaucher disease patients

To learn more about Gaucher disease and other lysosomal storage disorders, visit https://checkrare.com/gaucher-disease/ or https://www.gaucherdisease.org/