Genetic Disorder, Neuromuscular Deficits
Conditions
Keywords
AAV, Seroprevalence, Nab, Tab, neuromuscular, Genetic disorder
Brief summary
This study aims to assess the overall seroprevalence of neutralizing antibodies against different AAVs potentially used in gene therapy in patients with genetic neuromuscular diseases.
Detailed description
This research aims to determine the seroprevalence and immunological profiles of recent and/or emerging AAV capsids that could be used in future gene therapy programs. It will thus make it possible to: 1/ improve knowledge of the prevalence of anti-AAV antibodies (total and neutralizing) in these specific populations; 2/ identify the clinical, demographic or biological factors likely to influence this seroprevalence (age, sex, type of pathology, immunosuppressive treatment followed); 3/ to characterize the phenomena of cross-reactivity between different serotypes or variants of capsids, a major challenge for the design of new generations of vectors. The data generated will contribute to a better estimation of the populations potentially eligible for gene therapies, by making it possible to anticipate exclusion rates related to pre-existing immunity. They may also guide the rational selection of alternative capsids that are less immunogenic or evade cross-immunity, as well as the development of immunomodulation or re-assay strategies.
Interventions
DIAGNOSTIC_TESTDosage of AAV neutralizing antibodies
In each clinical site, the principal investigator will propose to his patients with neuromuscular disease of genetic origin to take a blood sample (4 mL of blood) to determine their level of immunity to certain AAVs used in gene therapy. The collected samples will be prepared and aliquoted on site and then sent frozen to the GENETHON laboratory for analysis. Only one sample per patient will be analyzed. All samples will be analyzed in batches.
Sponsors
Genethon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Pediatric patient 6 years of age or older or adult under 60 years of age with genetic neuromuscular disease 2. Informed patient who signed informed consent 3. No opposition from the holders of parental authority or guardian, for minor patients. 4. Affiliated/beneficiary of a national health insurance scheme
Exclusion criteria
* Gene or cell therapy treatment prior to blood collection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with anti-AAV neutralizing antibodies | Day 1 | The primary endpoint is the percentage of patients who tested positive for neutralizing antibodies against multiple AAVs that can be used in gene therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To estimate seroprevalence in subgroups of patients (age; type of neuromuscular disease; gender; immunosuppressive therapy) | Day 1 | Estimation of seroprevalence (positive or negative) of anti-AAV neutralizing antibodies in different subgroups (age, sex, type of neuromuscular disease, immunosuppressive therapy) |
| To analyze the co-prevalence between several AAV serotypes | Day 1 | Quantification of neutralizing antibody titers against various capsids using cellular tests |
| Analyze the potential correlation between the presence of neutralizing antibodies and total antibody titer using cellular tests and ELISA method | Day 1 | Prevalence of cross-reactions between multiple capsids |
Countries
France
Outcome results
None listed