Mitochondrial Diseases, Pearson Syndrome
Conditions
Keywords
Autologous stem cell transplantation, Mitochondrial Diseases, Pearson Syndrome, Rare Diseases
Brief summary
Mitochondrial diseases are a genetically heterogeneous group of disorders caused by mutations or deletions in mitochondrial DNA (mtDNA) displaying a wide range of severity and phenotypes. These diseases may be inherited from the mother (mitochondrial inheritance) or non-inherited. The latter are ultra-rare pediatric diseases caused by a mutation or deletion of mtDNA, which develop into a systemic multi organ disease and eventually death. MNV-BM-BLD is a therapeutic process for enrichment of patient's peripheral hematopoietic stem cells with normal and healthy mitochondria derived from donor blood cells. The process, called mitochondria augmentation therapy, aims to reduce the symptoms of mitochondrial diseases.
Interventions
BIOLOGICALCD34+ cells enriched with MNV-BLD
Transplantation of autologous stem cell enriched with MNV-BLD (blood-derived mitochondria)
Sponsors
Minovia Therapeutics Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Patient diagnosed with Pearson Syndrome, as verified by molecular identification of a defect in the mitochondrial DNA. 2. Normal maternal mitochondria as verified by mtDNA sequencing. 3. Males and females between 3 years or older and up to 18th birthday. 4. Patient is transfusion independent. 5. Patient has at least one of the following systematic involvements: 1. High baseline lactate levels 2. Episodes of metabolic crisis in the last year before pre-screening 3. Renal failure (not dependent on dialysis) or evidence of proximal tubulopathy 4. Growth retardation or failure to thrive
Exclusion criteria
1. Absence of detectable mitochondria mutation or deletion. 2. Patient or patient's mother have a positive test for microbiologic 3. Patient is unable to undergo leukapheresis. 4. Patient suffers from chronic severe infection, malignant disease or any other disease or condition that may risk the patient or interfere with the ability to interpret the study results. 5. Patient has been treated previously with any cell or gene therapy. 6. Patient has participated in another clinical treatment trial or received other experimental medications outside of a clinical trial within 1 month prior to start of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Treatment-related adverse events as assessed by CTCAE v5.0 following MNV-BM-BLD during a follow up period of 12 months post treatment. | 1 year | Severity will graded according to CTCAE, Version 5.0 |
| IPMDS (International Pediatric Mitochondrial Disease Scale) | 1 year | To compare the change in International Pediatric Mitochondrial Disease Scale (IPMDS) score during a follow up period of 12 months post treatment. IPMDS total score ranges from 0 to 243. The score is expressed as the percentage of items which were feasible to perform. The lower the score is, the higher the child's function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic crisis events occurrence compared to two years prior to the study. | 3 Years | To compare the changes during 3 years (2 years prior the study entry and 1 year follow up) |
| Change in renal function | 1 year | Measurement of blood creatinine in a serum sample |
| Change in Brain involvement | 1 year | Lactate peak as assessed by MRS |
| Height | 1 year | To compare the changes (in meters) to Baseline |
| Change in cardiac function | 1 year | Assessment of left ventricular ejection fraction via echocardiography |
| Monitoring for liver disease | 1 year | Measurement of Aspartate Aminotransferase and Alanine aminotransferase level |
| Weight | 1 year | To compare the changes (kilograms) to Baseline |
| Quantification of levels of normal mtDNA in blood and urine | 1 years | To compare the changes to Baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Control of blood glucose concentration | 1 year | Hemoglobin A1c% in whole blood |
| ATP content. | 1 year | To compare the changes to Baseline |
| Change in functional status | 1 year | Distance traveled during the 6MWT (meters) |
| Change in hematological parameter | 1 year | Measurement of hemoglobin level |
| Hospitalization events | 1 year | To compare the changes from medical history to 1 year follow up |
Countries
Israel
Outcome results
None listed