An Investigational One-Time Treatment for Mucopolysaccharidosis Type II (Hunter Syndrome)
REGENXBIO, a global leader in AAV gene therapy, is currently enrolling participants in a clinical trial of RGX-121, an investigational, one-time gene therapy for the potential treatment of mucopolysaccharidosis type II, also known as MPS II or Hunter syndrome. The clinical trial, called the CAMPSIITE™ Study, will evaluate the effect of RGX-121 in boys with neuronopathic MPS II1 between the ages of 4 months and 5 years.
About Hunter Syndrome
What is Mucopolysaccharidosis Type II (MPS II)?
MPS II, or Hunter syndrome, is a rare, genetic condition that occurs in approximately one out of every 100,000 to 170,000 male births.1
- People living with MPS II have a mutation in the gene that is responsible for making an enzyme called iduronate-2-sulfatase (IDS).1
- Cells need this enzyme to break down long chains of sugar molecules known as glycosaminoglycans (GAGs).1
- If GAGs build up in the body’s cells, they can cause progressive damage to many organs including the brain, ears, lungs, heart, stomach, intestines, bones, joints, mouth, and skin.2
- The damage resulting from GAG accumulation in the cells is irreversible, highlighting the importance of early diagnosis and treatment.4
- Currently approved treatments for Hunter syndrome do not address the impact of MPS II on the brain.3
Healthy Cell vs. Cell with MPS II
- Glycosaminoglycans (GAGs) Sugar molecules resulting from normal cell functions
- Normal DNA codes for a variety of enzymes that break down GAGs
Enzymes (these enzymes are in the lysosome, not floating around the cytoplasm – thus Lysosomal Storage Disorder)
- Enzymes break down the GAGs
CELL WITH NEURONOPATHIC MPS II
- DNA contains faulty code for producing a specific enzyme that breaks down GAGs
Cytoplasm (in the lysosome, not the cytoplasm)
- Enzymes only partially break down the GAGs, resulting in their buildup within the cell
- In patients with neuronopathic MPS II, GAG accumulation leads to tissue and organ damage throughout the body, including neurodegeneration.
Types of MPS II
Generally, there are two types of MPS II, which vary widely in terms of severity, rate of progression, and age of onset.
In attenuated MPS II, the disease progresses slowly, with minimal or no impact on the brain or on intellectual development.1
In neuronopathic MPS II, also known as severe MPS II, there is a faster rate of disease progression and significant impact on the brain and intellectual development.1 Neuronopathic MPS II accounts for up to 70%2 of incidences of the disease.6
In severe MPS II, or the neuronopathic form, a child may meet early developmental milestones, but the rate of skill acquisition slows early in development (usually by 12 to 24 months after birth). This delay becomes more apparent over time, with neurodevelopmental abilities (learning and understanding, expressive language) and fine motor skills moving outside of the normal range between 24 and 29 months. Skill acquisition generally plateaus around 5 to 6 years of age, with the child functioning at a developmental level similar to an unaffected 2- to 3-year-old.1-5
- Expressive language
Children with MPS II may display a variety of symptoms, depending on the age of onset and severity of the condition:1,2,6
- Recurring ear infections
- Umbilical or inguinal hernia (a bulge of part of the intestine through the opening in the abdominal muscles or in the groin region)
- Hydrocephalus (buildup of fluid deep in the brain)
- Thickening of nostrils and lips
- Macrocephaly (a larger than normal head)
- Macroglossia (a larger than normal tongue)
- Hepatosplenomegaly (enlarged spleen and liver)
- Hearing loss
- Enlarged tonsils
- Hoarse voice
- Sleep disturbances
- Short stature
- Stiff joints and limited joint motion
- Carpal tunnel syndrome
- Delayed growth
- Delayed appearance of teeth or wide spaces between teeth
- White growths on the skin
- Neurodevelopmental decline, intellectual disability
- Behavioral issues (hyperactivity, attention issues, destructiveness, lack of fear)
For more information about MPS II, visit the following links:
- National MPS Society (U.S.) (English)
- Project Alive (English)
- National Organization for Rare Disorders (NORD) (English)
- Casa Hunter (Brazil) (English, Portuguese)
- Canadian MPS Society for Mucopolysaccharide & Related Diseases (English)
- Orphanet (Czech, Dutch, English, French, German, Italian, Polish, Portuguese, Spanish)
For more information about MPS II, visit the following links:
Casa Hunter (Brazil) (English, Portuguese)
Orphanet (Czech, Dutch, English, French, German, Italian, Polish, Portuguese, Spanish)
- Rare Disease Database: Mucopolysaccharidosis type II. NORD – National Organization for Rare Disorders, Inc.; 2021. https://rarediseases.org/rare-diseases/mucopolysaccharidosis-type-ii-2/.
- Escolar ML, Jones SA, Shapiro EG, Horovitz DDG, Lampe C, Amartino H. Practical management of behavioral problems in mucopolysaccharidoses disorders. Mol Genet Metab. 2017;122:35-40.
- D’Avanzo F, Rigon L, Zanetti A, Tomanin R. Mucopolysaccharidosis type II: one hundred years of research, diagnosis, and treatment. Int J Mol Sci. 2020;21:1258.
- Muenzer J, Bodamer O, Burton B, et al. The role of enzyme replacement therapy in severe Hunter syndrome – an expert panel consensus. Eur J Pediatr. 2012;171:181-188.
- Escolar M, Phillips D, Cho Y, Mulatya C, Nevoret M-L, Poe M. Natural history of neurodevelopment in neuronopathic mucopolysaccharidosis type II (MPS II): Mullen Scales of Early Learning (MSEL) visual reception, expressive and receptive language and fine motor scale developmental trajectories. Presented at 2022 annual symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM), Freiburg, Germany, August 2022. Abstract SSIEM22-2814.
- Scarpa M. Mucopolysaccharidosis type II. GeneReviews® [Internet]; 2018. https://www.ncbi.nlm.nih.gov/books/NBK1274/.
About RGX-121 Gene Therapy
What are genes and gene therapy?1-3
Every cell in the human body contains chromosomes made up of genes. These genes consist of DNA, which provides instructions that tell the body how to make proteins, which are an essential building-block for our bodies. The human body contains thousands of genes.
Gene therapy is a treatment that involves the introduction, removal, or change in genetic material in a person’s cells. There are various approaches to gene therapy:
The delivery of a gene to a person, allowing that person’s body to produce a functional protein (also sometimes called gene replacement). RGX-121 uses this approach.
The insertion, replacement, or deletion of faulty DNA within a gene.2-3
The modification of RNA (a DNA-like molecule that helps the cell create proteins from genes) to block the production of dysfunctional protein from a mutated gene.
What is NAV® Technology?
REGENXBIO’s gene therapies are being investigated in clinical trials and are designed to deliver working genes to cells using adeno-associated virus (AAV) vectors as delivery “vehicles.” AAV vectors are modified viruses that cannot increase their numbers or reproduce themselves and are not known to cause disease in humans.
Our investigational gene therapies all use viral vectors from our proprietary gene delivery platform, which we call the NAV® Technology Platform. Thousands of patients have received AAV gene therapies derived from our NAV Technology Platform.
What is RGX-121?
RGX-121 is an investigational, one-time gene therapy for the potential treatment of MPS II. It is designed to use the NAV® AAV9 vector to deliver the human iduronate-2-sulfatase (IDS) gene directly to the fluid surrounding the brain, which is known as the cerebrospinal fluid (CSF).
- Once the NAV® AAV9 vector delivers the IDS gene to cells in the brain, the cells may begin making the needed I2S enzyme and could provide a permanent source of I2S in the central nervous system (CNS) which consists of the brain and spinal cord.
- Continuous production of the enzyme may prevent neurodevelopmental decline in children who receive the gene therapy early in life and may stop the damage from getting worse in children who receive the gene therapy at an older age.
- Unlike currently available treatments for MPS II, RGX-121 may cross the blood-brain barrier (BBB), a protective network of blood vessels and cells which separates the CNS from the rest of the body. By crossing the BBB from the CNS to reach the rest of the body, RGX-121 may address the systemic effects (those affecting the body as a whole) of MPS II.4
Transporter (Adeno-associated viral vector, AAV)
- Viral DNA is removed
- Functional human IDS gene is inserted
- Treatment is delivered into the central nervous system, guided by CT scan while patient is asleep
- Vector binds to cell membrane
- Vector is internalized by cell in a vesicle (a small liquid sac) and transported to nucleus
- Vector releases functional gene into nucleus
- Cell produces missing enzyme from healthy gene
- Full enzyme complement can now break down GAGs that would otherwise
- Resultant enzyme is secreted and taken up by other cells
RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, and Fast Track designations from the U.S. Food and Drug Administration, as well as Oprhan Drug Designation from the European Medicines Agency (EMA).
- Different approaches. American Society of Gene + Cell Therapy; 2022. https://patienteducation.asgct.org/gene-therapy-101/different-approaches.
- Petrich J, Marchese D, Jenkins C, Storey M, Blind J. Gene replacement therapy: a primer for the health-system pharmacist. sJ Pharm Pract. 2020;33(6):846-855.
- Adachi H, Hengesbach M, Yu Y-T, Morais P. From antisense RNA to RNA modification: therapeutic potential of RNA-based technologies. Biomedicines. 2021;9(5):550.
- Pukenas B, Papisov M, Buss N, et al. Intracisternal administration of AAV9 gene therapies to target the central nervous system. Presented at WORLDSymposium™ 2021 Virtual Scientific Meeting, February 9, 2021, Poster #207.
We are currently enrolling children with neuronopathic Hunter syndrome (MPS II) who are older than 4 months and less than 5 years of age in the CAMPSIITE™ Study, a Phase I/II/III, multicenter, open-label, single-arm study of RGX-121.
Participating in CAMPSIITE
If your child has been diagnosed with MPS II and your family is interested in participating in the CAMPSIITE Study, please speak with the doctor who treats your child for MPS II or contact one of the study locations. CAMPSIITE is a global trial, which is expected to include sites in the United States, Brazil and Canada.
Initial Meeting with Study Doctor
Parents of children who may be eligible will need to meet with a study doctor to review the details of the study and the informed consent process.
The study doctor and team will discuss your child's health, basic information about the study, and possibly request medical records.
If eligible and you decide to enroll your child
If it appears that your child may qualify, the study team may schedule an initial screening visit to begin determining eligibility and review the Informed Consent Form with you in detail. The process of determining eligibility can take a few weeks.
Main Study Duration
If your child qualifies and you decide to enroll them in this study, participation in the main part of the study will last about 2 years. During this time, your child will visit the clinic multiple times per year for various tests and assessments.
At the end of the main study, your child will be encouraged to enroll in a long-term follow-up study, which seeks to understand the long-term safety and efficacy of RGX-121.
Visit ClinicalTrials.gov using the identifier NCT03566043 for more information about this study including eligibility criteria.
Find a study location near you!
The CAMPSIITE™ Study is expected to include sites in the United States, Brazil, and Canada.
For study-specific questions, such as eligibility, please contact a study site. Contact information for study sites can be found at ClinicalTrials.gov (identifier # NCT03566043).
If you are a healthcare provider and would like more information on our studies for patients
with MPS II, please contact us at firstname.lastname@example.org.