Karen Bean, Health Economist at Orchard Therapeutics, discusses healthcare resource use for patients with Mucopolysaccharidosis type III (MPS III).

MPS III, also known as Sanfilippo syndrome, is a genetic disorder characterized by the inability to break down glycosaminoglycans, specifically, heparan sulfate. Affected individuals can have severe neurological symptoms, including progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time. MPS IIIA is the most severe subtype and is associated with the earliest onset and the most rapidly progressive disease course. MPS IIIA patients typically become wheelchair bound by their teenage years and ultimately regress to a prolonged vegetative state until death, which occurs in the second decade of life.

The objective of this study was to explore the pattern of healthcare resource use from a cohort of US patients with a confirmed MPS III diagnosis.

ICD-10-CM codes were identified from 2017 to 2024 for a cohort of 735 patients. On average there were 879 records per patient, and the most common symptom codes were epilepsy (37%), autistic disorder (32%), diarrhea (30%), intellectual disabilities (29%), sleep apnea and abnormalities with gait and mobility (both 26%). The most common procedure codes included wheelchair accessories (42%), speech/hearing therapy (31%) and physiotherapy (31%).

Longitudinal data from birth are available for a sub-cohort of 103 patients with median age at diagnosis of 4 to 5 years old. Data from this cohort show a significant delay from symptom onset to diagnosis.

These results highlight the variety and intensity of healthcare interactions and interventions required for patients with MPS III, necessitating a multidisciplinary team to manage the multifaceted aspects of the disease.

Chapters:
Introduction 00:00
MPS III Overview 00:30
Diagnostic Pathways 1:53
Healthcare Resource Use Study 3:25
Comparison to Other Diseases 7:38
Take Home Message 8:12

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Ida Vanessa D. Schwartz, MD, PhD, HCPA, Professor of Genetics at the Federal University of Rio Grande do Sul, discusses two-year follow up from GALILEO-1 of FLT201 gene therapy in adults with Gaucher disease type 1 (GD1).

Gaucher disease refers to a group of inherited metabolic diseases in which harmful amounts of lipids accumulate in various cells and tissues in the body. Signs and symptoms vary widely among affected individuals and may include skeletal disorders, hepatosplenomegaly, liver malfunction, anemia, low platelet counts, bone problems, and neurological problems. There are different types of Gaucher disease classified according to specific features and severity, GD1 being the most common. It is caused by genetic changes in the GBA gene.

FLT201 is an investigational AAV gene therapy for GD1, comprising of a proprietary, liver-tropic capsid (AAVS3), with a unique transgene encoding GCase85, a novel engineered variant of β-glucocerebrosidase (GCase) under control of a liver-specific promoter. The treatment is designed to deliver continuous, durable endogenous expression of GCase85, eliminating the need for chronic treatment with enzyme replacement therapy (ERT) or superficial radiation therapy (SRT).

The GALILEO-1 clinical trial is the first-in-human study of FLT201, which enrolled six adults with GD1 on stable treatment with either ERT or SRT for at least two years prior to enrollment. Patients received a single IV infusion of FLT201 at a dose of 4.5 x10^11 vg/kg and follow-up duration ranged from 20 to 29 months. All patients are currently enrolled in the long-term follow-up study, GALILEO-2.

Four participants discontinued ERT/SRT following administration of FLT201 and remained off their background therapy. In these patients, FLT201 was observed to provide durable long-term GCase85 expression with cross-correction of peripheral blood leukocytes. Maintenance or improvement of hemoglobin and platelet count, stability in liver and spleen volumes, and clearance of lyso-Gb1 has been sustained or further reduced. Improvements were seen in one or more efficacy assessment in all four patients.

FLT201 administration was well-tolerated in all patients with no infusion-related reactions reported. The overall safety profile is favorable, with no treatment-related serious adverse events and only mild transient ALT elevations considered related to therapy were observed.

Chapters:
Introduction 00:00
Gaucher Landscape Overview 00:38
FLT201 Gene Therapy 1:58
Study Results 3:21
Next Steps 5:25
Take Home Message 5:52

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Kim Stephens, DBA, Executive Director of the Muenzer MPS Research & Treatment Center, discusses a survey of clinical guidelines for mucopolysaccharidosis II (MPS 2; Hunter syndrome).

MPS II is an inherited disorder of carbohydrate metabolism that occurs almost exclusively in males. It is characterized by distinctive facial features, a large head, hydrocephalus, hepatosplenomegaly, umbilical or inguinal hernia, and hearing loss. Individuals with this condition may additionally have joint deformities and heart abnormalities involving the valves. MPS II is caused by genetic changes in the IDS gene.

The purpose of this study was to collect information on consensus statements to inform treatment guidance for MPS II, whose clinical guidelines were last updated in 2003. A Delphi survey was created, consisting of questions related to overall care and specialized care in neurology, cardiology, orthopedics, gastroenterology, pulmonology, ENT, and other relevant fields. A total of 29 practitioners participated in the survey.

Results include:

- 74% of respondents said that enzyme replacement therapy (ERT) should be started before the presentation of physical symptoms in an attenuated phenotype.
- 100% of respondents said ERT should be started before the presentation of physical symptoms in a severe phenotype.
- In the absence of a definitive genotype, 52% responded that IV ERT should be started before the onset of physical symptoms.
- 23% responded that drug antibodies in a patient with MPS II receiving IV ERT should be tested every year.
- 84% responded that HSCT should be considered for patients with MPS II who are predicted to be severe.
- 48% said that neuromonitoring should be considered for MPS II anesthesia cases that last less than 2 hours, while 44% said no.
- Most respondents said that neuromonitoring should be used for all extended MPS II procedures/surgery under anesthesia over 2 hours in duration, regardless of spine involvement.
- 21% said yes, 25% said no, and the rest responded “not in my area” to whether or not tarsal tunnel release be recommended for patients who are toe walkers.

New guidelines are necessary given the rarity of the disease and lack of specialists. These results may help guide practitioners in the creation of updated guidelines for MPS II.

Chapters:
Introduction 00:00
Considering Therapies for MPS II 00:31
Importance of Clinical Guidelines 1:53
Changes to Guidelines 3:17
Diagnosis Within Guidelines 4:28
Newborn Screening 5:25
MPS II Biomarkers 6:03
Take Home Message 6:55
Personal Journey 8:11
Advice for Newly Diagnosed Families 9:39

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Sophia Ceulemans, MS, Medical Science Liaison at GeneDx, offered a high-level overview of the problem of unexplained epilepsy and the rapidly advancing field of genetic testing for this challenging disorder. Ms. Ceulemans co-authored the current guidelines from the National Society of Genetic Counselors (NSGC).

#genetictesting #epilepsy #rarediseases #neurology

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Sophia Ceulemans, MS, Medical Science Liaison at GeneDx, provides an overview of unexplained epilepsy.

#genetictesting #epilepsy #rarediseases #neurology

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Sophia Ceulemans, MS, Medical Science Liaison at GeneDx, discusses genetics in unexplained epilepsy.

#genetictesting #epilepsy #rarediseases #neurology

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Sophia Ceulemans, MS, Medical Science Liaison at GeneDx, discusses diagnostic pathways in unexplained epilepsy.

#genetictesting #epilepsy #rarediseases #neurology

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Sophia Ceulemans, MS, Medical Science Liaison at GeneDx, discusses how diagnosis has evolved in unexplained epilepsy.

#genetictesting #epilepsy #rarediseases #neurology

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Sophia Ceulemans, MS, Medical Science Liaison at GeneDx, explains the importance of genetic testing in unexplained epilepsy.

#genetictesting #epilepsy #rarediseases #neurology

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