Clinical trial NCT06507215: Dysferlinopathy Protein in Peripheral Blood Monocytes.
Official title: Cross-sectional Study to Evaluate the Frequency of Dysferlinopathy Carriers in the Caucasian Population Using a Test for Detecting the Dysferlin Protein in Peripheral Blood Monocytes.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Muscular Dystrophies
Limb-Girdle Muscular Dystrophy Type 2B
Miyoshi Myopathy
Distal Myopathy With Anterior Tibial Onset
Keywords: muscular dystrophy
dysferlin
Limb-Girdle Muscular Dystrophy Type 2B
Miyoshi Myopathy
Distal Myopathy with Anterior Tibial Onset
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
First posted: 2024-07-18
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study focuses on individuals with dysferlinopathies, a heterogeneous group of autosomal recessive muscular dystrophies caused by mutations in the DYSF gene. It examines the effect of vitamin D3 treatment on dysferlin expression in vitro using HL60 cells, monocytes, and myotubes from controls and carriers of a single DYSF mutation. Additionally, an observational study with oral vitamin D3 in a cohort of 21 carriers demonstrates a significant increase in dysferlin expression in treated monocytes compared to untreated carriers. These findings suggest significant therapeutic implications, emphasizing the potential of combining molecular strategies with vitamin D3 supplementation to elevate dysferlin expression to non-pathological levels.

Brief summary: The objective of the study is to answer the following important questions. Deficiency of the dysferlin protein is the cause of a very rare limb-girdle muscular dystrophy (LGMD-2B) that leads to significant disability. This disease is caused by mutations in the dysferlin gene. It is a recessive inherited disease, meaning that both copies of the gene must have mutations for the disease to develop. This study aims to analyze the frequency of carriers of a mutation in the DYSF gene in the Caucasian population. To achieve this, The investigator analyzed the blood of 100 healthy volunteers from their local area, quantifying the dysferlin protein in peripheral blood monocytes.


Eligibility criteria: Inclusion Criteria:

* Individuals diagnosed with dysferlinopathies.
* Carriers of a single mutation in the DYSF gene.
* Participants who are willing to undergo treatment with oral vitamin D3.
* Subjects who can provide informed consent for participation in the study.
* Controls and carriers willing to participate in in vitro studies using HL60 cells, monocytes, and myotubes.

Exclusion Criteria:

* Individuals with conditions or medications that could interfere with the study outcomes of dysferlin expression.
* Participants who are unwilling or unable to adhere to the study protocol for the duration of the study period.
* Pregnant or breastfeeding women.
* Individuals with known allergies or adverse reactions to vitamin D3 supplements.
* Subjects with severe concurrent illnesses that may impact the study's objectives or their ability to participate effectively.

Primary outcomes:
measure: Dysferlin Expression Levels by age and gender
timeFrame: 1 month
Secondary outcomes:
measure: Identification of Carries by Protein Level
timeFrame: 1 month
measure: Percentage of Predicted Carriers Showing Specific Genetic Mutations
timeFrame: 1 month
measure: Percentage of DNA Methylation in Target Gene
timeFrame: 1 month
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Eduard Gallardo Vigo
state: Cataluña
Study officials:
References: