Ozlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and Raphael Schiffmann, MD, of the Texas Christian University, discuss best practices to identify and treat neurologic problems associated with lysosomal disorders.

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 complete the program and obtain credit, visit https://checkrare.com/learning/p-lysosomal-disorders-and-the-brain/ 
Support for this educational activity provided by Takeda and Ultragenyx.

Learning Objectives

• After participating in the activity, learners should be better able to:
• Describe the role of the neurologist in the team approach to care
• List best practices to assess neurologic and cognitive involvement  in persons with LDs
• Cite best practices to assess developmental delay and regression in pediatric patients with suspected LDs
• Describe the latest clinical research to improve central outcomes in persons with LDs and central nervous system involvement
Faculty
Ozlem Goker-Alpan, MD, 
Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC), Fairfax, VA 

Raphael Schiffmann, MD
Texas Christian University,
Fort Worth, TX

Disclosures
AffinityCE staff, LDRTC staff, planners, and reviewers, have no relevant financial relationships with ineligible companies to disclose. Faculty disclosures, listed below, will also be disclosed at the beginning of the Program.

Ozlem Goker-Alpan MD
Dr. Goker-Alpan is on the Advisory Board/Consultant for Chiesi, Takeda, Sanofi, Prevail/Lilly, Sparks Therapeutics, Uniqure, Exegenesis, Astellas, Freeline, Team Sanfilippo. She receives grants/research support from Chiesi, Sanofi, Takeda, Prevail/Lilly, Spark Therapeutics, Amicus, Freeline, Sangamo, Cyclo, Odorsia, $DMT, Homology, Protaliz. She is on the speaker bureau for Sanofi, Takeda, Amicus, Chiesi.

Raphael Schiffman, MD
Dr. Schiffmann is consultant for Amicus Therapeutics, Protalix Biotherapeutics, Chiesi Farmaceutici and 4D Molecular Therapeutics

Mitigation of Relevant Financial Relationships
AffinityCE adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity. Conflicts of interest for presenting faculty with relevant financial interests were resolved through peer review of content by a non-conflicted reviewer.
 
Physicians
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physician Assistants
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physician Assistants should claim only the credit commensurate with the extent of their participation in the activity.

Nurses
Continuing Nursing Education is provided for this program through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation (ANCC). This activity provides a maximum of 1 hours of continuing nursing education credit.

Nurse Practitioners
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Nurse practitioners should cla...

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Scott Baver, PhD, Vice President of Medical Affairs at ITF Therapeutics, discusses new data on the use of Duvyzat (givinostat) for patients with Duchenne muscular dystrophy (DMD).

DMD is a rare neuromuscular disorder characterized by progressive muscle wasting. DMD occurs primarily in males, though in rare cases may affect females. The symptoms of DMD include progressive weakness and atrophy of both skeletal and heart muscle. Early signs may include delayed ability to sit, stand, or walk and difficulties learning to speak. DMD is caused by genetic changes in the DMD gene that is involved in the synthesis of dystrophin.

Givinostat is an orally administered histone deacetylase (HDAC) inhibitor that regulates excessive HDAC activity in DMD muscles and restores expression of key genes and biological processes essential for muscle maintenance and repair. It is currently indicated for treatment of patients with DMD ages 6 years and older.

New data on the use of givinostat in patients with DMD was presented at the 2025 Neuromuscular Study Group (NMSG) Annual Scientific Meeting.

Chapters:
Introduction 00:00
DMD Landscape Overview 00:28
Givinostat Overview 1:24
Data Presented at NMSG 2:46
Next Steps 5:00
Take Home Message 5:45

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Jai Radhakrishnan, MD, Nephrologist and Professor at Columbia University Medical Center, discusses diagnosis and treatment of IgA nephropathy (IgAN).

IgAN is an autoimmune kidney disorder characterized by the settling of IgA protein in the kidneys. In most instances, the cause of this condition is unknown; however, certain disorders have been linked with IgAN, such as cirrhosis of the liver, celiac disease, and HIV infection. Familial IgAN is linked to genetic material on the long arm of chromosome 6.

In the early stages, IgAN has no symptoms making diagnosis difficult. The first sign of this condition may be blood in the urine and the condition can result in end-stage kidney disease. Up to 50% of patients with IgAN with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis. Due to the severity of late-stage IgAN, early diagnosis is crucial in effectively treating and managing patients.

Within the last year, the U.S. Food and Drug Administration (FDA) has approved two treatments for this indication; Fabhalta (iptacopan) and Vanrafia (atrasentan). Iptacopan is an oral factor B inhibitor that selectively blocks the alternative pathway of the complement system while Atrasentan is a selective endothelin A receptor antagonist designed to reduce proteinuria.

The introduction of these novel treatments indicates a growing therapeutic landscape and the need for further education of the diagnosis and treatment of IgAN. The heterogeneity of the disease requires personalized treatment plans and effective communication between patients and physicians (i.e., understanding the need for frequent testing and strict following of diet, exercise, and treatment plan).

Dr. Radhakrishnan also emphasizes the importance of participation in clinical trials in the development and approval of new treatments. He notes that the more patients participate, the more knowledge can be learned and effective management options can be developed and implemented, changing the landscape of the disease.

Chapters:
Introduction 00:00
IgAN Overview 1:10
Signs and Symptoms 2:35
IgAN Management 3:20
Advice to Physicians 7:12
Importance of Clinical Trials 8:53

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Join rare disease leaders in D.C. Oct. 19-21.

Shape the future of rare disease treatments, research, and policy at the 2025 NORD® Rare Diseases and Orphan Products Breakthrough Summit.® Learn more and register at nordsummit.org.

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May Lee Tjoa, PhD, Senior Global Medical Affairs Leader: Nipocalimab and Maternal-Fetal Immunology at Johnson & Johnson, discusses data on hemolytic disease of the fetus and newborn (HDFN) from the 2025 ISUOG World Congress on Ultrasound in Obstetrics and Gynecology.


HDFN is a rare condition characterized by the destruction of fetal red blood cells due to maternal-fetal blood group incompatibility. The condition may occur in persons with Rh or ABO blood types. Rh incompatibility usually affects subsequent pregnancies due to maternal sensitization that occurs in the first pregnancy. This leads to more severe complications such as intrauterine hydrops fetalis in later pregnancies. ABO incompatibility can impact the first pregnancy due to preexisting maternal antibodies. Symptoms of disease in newborns include lethargy, jaundice, hepatosplenomegaly, and signs of hydrops fetalis.

There are currently no approved therapies for the treatment of HDFN. Pregnancies affected by severe HDFN may need repeated intrauterine transfusions (IUTs), and/or invasive surgical procedures that may be associated with increased rate of fetal mortality and premature birth. Below are summaries of three studies presented at the World Congress highlighting the need for improved therapy options for this rare condition.

Chapters:
Introduction 00:00
HDFN Overview 1:34
Outcomes of Intrauterine Transfusion 3:33
Costs Associated With HDFN 4:55
Take Home Message 7:09
FNAIT Patient Experiences 8:52

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Amit Mehta, MD, Medical Oncologist, discusses data that led to the approval of Wayrilz (rilzabrutinib) for adult patients with immune thrombocytopenia (ITP).

ITP is a bleeding disorder characterized by low levels of platelets. It is an autoimmune disorder in which abnormal antibodies attach to the platelet membranes. Symptoms may include bruising, nosebleed or bleeding in the mouth, bleeding into the skin, and abnormally heavy menstruation. Rarely, ITP may become a chronic ailment in adults and reappear, even after remission.

The U.S. Food and Drug Administration (FDA) recently approved rilzabrutinib for adults with persistent or chronic ITP who have had an insufficient response to previous treatment. The approval was based on data from the LUNA 3 clinical trial (NCT04562766), a phase 3, randomized, multicenter study evaluating the safety and efficacy of rilzabrutinib versus placebo in adult and adolescent patients with persistent or chronic ITP. Results from the adult group of 202 patients were presented at the 66th American Society of Hematology Annual Meeting and Exposition. The adolescent part is ongoing.

Rilzabrutinib is an oral, reversible, Bruton’s tyrosine kinase (BTK) inhibitor that addresses the underlying cause of ITP through multi-immune modulation and targeting various pathways across the immune system.

Patients who achieved platelet count response at 12 weeks were eligible to continue the full 24-week double-blind period. This included 64% of patients in the rilzabrutinib arm and 32% of patients in the placebo arm.

In the rilzabrutinib arm, 23% of patients experienced statistically significant durable platelet response at week 25 compared to 0% in the placebo arm. Rilzabrutinib patients also experienced a faster time to first platelet response of 36 days compared to the platelet response not being reached in the placebo group. The treatment group also showed a longer duration of platelet response of 7 weeks compared to 0.7 weeks in the placebo group.

Patients in the rilzabrutinib arm also reported an overall 10.6-point improvement in nine health-related quality of life measures, compared to a 2.3-point increase in the placebo group.

The most common adverse reactions are diarrhea, nausea, headache, abdominal pain, and COVID-19.

Chapters:
Introduction 00:00
ITP Overview 00:31
Current Management 2:35
Rilzabrutinib Overview 4:37
LUNA 3 Clinical Trial 8:03
Take Home Message 11:21

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Jannine Williams, Compound Development Team Leader at Johnson & Johnson, discusses key takeaways from studies on hemolytic disease of the fetus and newborn (HDFN) presented at ISUOG World Congress 2025.

HDFN is a rare condition characterized by the destruction of fetal red blood cells due to maternal-fetal blood group incompatibility. The condition typically involved the Rh or ABO blood types. Rh incompatibility usually affects subsequent pregnancies due to maternal sensitization that occurs in the first pregnancy. This leads to more severe complications such as intrauterine hydrops fetalis in later pregnancies. ABO incompatibility can impact the first pregnancy due to preexisting maternal antibodies. Symptoms of disease in newborns include lethargy, jaundice, hepatosplenomegaly, and signs of hydrops fetalis.

There are currently no approved therapies for the treatment of HDFN. Pregnancies affected by severe HDFN may need repeated intrauterine transfusions (IUTs), invasive and technically complex surgical procedures that may be associated with increased rate of fetal mortality and premature birth.

Chapters:
Introduction 00:00
HDFN and its Unmet Needs 00:39
Causes of Disease 4:01
Signs and Symptoms 4:35
Risk of Disease 5:29
Nipocalimab Clinical Trial 6:05
ISUOG Presentations 6:35
Take Home Message 9:13

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Mike Flanagan, PhD, Chief Scientific Officer at Avidity Biosciences, discusses new data from the EXPLORE44 open-label extension of del-zota for treatment of patients with Duchenne muscular dystrophy (DMD) amenable to exon 44 skipping.

DMD affects the muscles, leading to progressive muscle wasting. DMD occurs primarily in males, though in rare cases may affect females. The symptoms of DMD include progressive weakness and atrophy of both skeletal and heart muscle. Early signs may include delayed ability to sit, stand, or walk and difficulties learning to speak. DMD is caused by genetic changes in the DMD gene.

Del-zota is a proprietary monoclonal antibody that binds to transferrin receptor 1 conjugated to a phosphorodiamidate morpholino oligomer (PMO) targeting exon 44, enabling dystrophin production. The EXPLORE44 clinical trial (NCT05670730) was a phase 1/2 evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-zota in 26 patients with DMD mutations amenable to exon 44 skipping. Participants then had the option to enroll in the EXPLORE44 open-label extension study.

The open-label extension (NCT06244082) was a multi-center trial evaluating the long-term safety, tolerability, pharmacokinetics, and pharmacodynamics, and efficacy of del-zota in 39 total patients with DMD amenable to exon 44 skipping.

Results with del-zota demonstrated statistically significant increases of about 25% of normal in dystrophin production and restored total dystrophin up to 58% of normal. Creatine kinase levels were also rapidly reduced by greater than 80% compared to baseline and were sustained at near normal levels throughout the duration of evaluation (up to 16 months). Half of the participants also had creatine kinase levels within the normal range at one year of treatment.

Additionally, patients in the open-label extension demonstrated improvements in four-stair climb by 2.1 seconds from baseline, 10-meter walk/run test by 0.7 seconds from baseline, time to rise from floor by 3.2 seconds from baseline, North Star Ambulatory Assessment remained stable, and performance of upper limb by 1.5 points from baseline. Compared to natural history data, these results were significant improvements.

Finally, del-zota continued to demonstrate favorable long-term safety and tolerability in this open-label extension. The majority of treatment emergent adverse events were mild or moderate and the most common were upper respiratory tract symptoms, diarrhea, fall, back pain, and headache. There was one discontinuation following an event of hypersensitivity.

Next steps involve plans for a Biologics License Application (BLA) submission for Accelerated Approval to the U.S. Food and Drug Administration (FDA) by the end of 2025.

Chapters:
Introduction 00:00
DMD Landscape Overview 00:28
Del-Zota Overview 2:12
Clinical Trial Data 2:57
Next Steps 6:05

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Clint Allen, MD, Senior Investigator, and Scott Norberg, DO, Associate Research Physician at Center for Cancer Research at the National Cancer Institute, discuss results from a study testing the safety and efficacy of zopapogene imadenovec to treat patients with recurrent respiratory papillomatosis (RRP).

RRP is a rare viral disease where tumors grow in the respiratory tract. The tumors can cause a hoarse voice, chronic cough, and difficulty breathing. These tumors rarely become cancerous, but can cause long-term airway and voice complications. RRP is caused by two types of human papillomaviruses (HPV), HPV 6 and HPV 11. There are currently no systemic treatments for this condition.

A recent study published in The Lancet Respiratory Medicine aimed to assess the safety and clinical activity of zopapogene imadenovec (PRGN 2012) in adult patients with RRP. Zopapogene imadenovec is a gorilla adenovirus vector-based gene therapy that targets robust T-cell immunity specific to HPV 6 or 11.

The study was a single-center, single-arm, phase 1/2 trial (NCT04724980) enrolling 38 patients who received a 12-week treatment course. The primary outcome measure was complete response rate, defined as the percentage of patients who did not require an intervention to control RRP in 12 months following treatment.

Of the 35 patients treated at the recommended phase 2 dose (5×1011 particle units), 51% demonstrated a complete response with the median duration of complete response yet to be reached. Complete responses were durable in 83% of those who achieved complete response, requiring no interventions in 12 months following treatment with a median follow up of 22 months.

Additionally, five patients had a partial response, defined as a 50% or greater reduction in clinically indicated interventions after treatment compared with before treatment. The objective response rate was 66%. Adverse events were mild and included grades 1-2 injection site reaction, fatigue, chills, and fever.

Based on these positive results, the U.S. Food and Drug Administration (FDA) approved zopapogene imadenovec in August 2025.

Chapters:
Introduction 00:00
RRP Overview 1:29
Pathophysiology and Natural History 2:46
Zopapogene Imadenovec Overview 4:28
Clinical Trial 6:15
Impact on Management 10:13

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