Leigh Syndrome (Maternally Inherited, MILS)cureMILSNCT06967831
Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells
An observational study of Leigh Syndrome (Maternally Inherited, MILS) and Leigh Syndrome (AR, AD, XR), run by Charite University, Berlin, Germany at 2 sites in Germany.
Trial summary
In this project, the investigators are using iPSC lines derived from patients with Leigh syndrome that carry mutations in the mitochondrial (mtDNA) and in the nuclear DNA (nDNA) to reprogram them into neural progenitor cells and into dopaminergic neurons. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leigh Syndrome (Maternally Inherited, MILS), Leigh Syndrome (AR, AD, XR)
- What is being tested?
- skin biopsy, generation of iPSCs and blood drawing
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 2 sitesGermany
- Study dates
- 1 Mar 2020to 28 Feb 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients (male and female) who are affected by Leigh syndrome and carry a pathogenic mutation in a gene known to be associated with Leigh syndrome
Inclusion Criteria: 1. Patient has a disease causing mutation in one of the genes causing Leigh syndrome if mutated, 2. Patient has the characteristic cranial MRI abnormalities of Leigh syndrome
Exclusion Criteria: 1. bleeding disorder that precludes a skin biopsy, 2. retraction of consent
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany2 sites, 2 recruiting
- Recruiting
Charite - Universtaetsmedizin Berlin
Berlin, State of Berlin, 13353
Markus Prof. Dr. Schuelke, MD, +49 30 4505 66468, markus.schuelke@charite.de
- Recruiting
Universitätsklinikum Düsseldorf
Düsseldorf, North Rhine-Westphalia, 40225
Alessandro Prof. Dr. Prigione, MD, +49 211 81 17687, alessandro.prigione@hhu.de
About this study
Official title: Using iPSC Derived Human Basal Ganglia Neurons From Patients With Leigh Syndrome for Metabolic Studies, Assay Development, and Drug Repurposing.
In this project, the investigators are using iPSC lines derived from patients with Leigh syndrome that carry mutations in the mitochondrial (mtDNA) and in the nuclear DNA (nDNA) to reprogram them into neural progenitor cells and into dopaminergic neurons. The researchers are using this experimental system to screen FDA (Food and Drug Administration, USA) and EMA (European Medicines Agency) approved drugs for a positive effect on Leigh patient-derived neuronal cells (drug repurposing) using various biochemical, optic, and morphological outcome measures. Confirmed positive hits may be used for compassionate off-label use in Leigh patients when no standard treatment is available.
Read the detailed description
Leigh syndrome is a rare severe hereditary neurological disease that typically manifests during early childhood and is characterized by the progressive loss of motor and intellectual skills. A hallmark of the disease is the degeneration of neuronal cells in the brainstem and in the basal ganglia, particularly the dopaminergic neurons therein. The genetic underpinnings of this condition are multifaceted, encompassing mutations in both nuclear genes and in those contained within the mitochondrial DNA (mtDNA). The investigators hypothesize that these mutations share a common principle in their capacity to induce dysfunction of mitochondrial processes and of bioenergetic metabolism. The precise mechanism underlying neuronal death remains to be elucidated as researchers presently lack suitable disease models. Notably, the generation of a mouse model for mtDNA mutations has not been achieved, necessitating the exclusive reliance on patient derived material for research into the pathogenesis of these diseases. Moreover, there are currently no pathogenesis-based treatment approaches that have been demonstrated to improve patients' symptoms. Here, the investigators aim to utilize reprogramming technologies to engineer innovative human-derived disease models for research into Leigh syndrome. To this end, the investigators plan generating induced pluripotent stem cells (iPSCs) from fibroblasts of different Leigh syndrome patients who carry both nuclear (e.g. in SURF1) and mtDNA mutations (e.g. in MT-ATP6). Pluripotent progenitor cells offer a novel approach to better understand the pathogenesis of genetic diseases. In the case of Leigh syndrome, accessible cells, such as skin or blood cells, are almost never clinically affected. However, the nerve cells of the basal ganglia, which cannot be obtained via biopsies, are predominantly affected. The underlying mechanisms by which these dopaminergic neurons are particularly vulnerable to mitochondrial dysfunction and subsequent death remain to be elucidated. The objective of this study is to differentiate these induced pluripotent stem cells (iPSCs) into neural precursor cells (NPCs) and then into a neuronal cell population that is predominant inside the basal ganglia, such as dopaminergic neurons. Subsequently, a detailed analysis of these neurons will be conducted to ascertain mitochondrial and metabolic parameters, with the objective of elucidating neuronal changes associated with mitochondrial disease. Consequently, based on the identified dysfunction, imaging test procedures will be developed that are aimed at high sample throughput. This should enable high-throughput screening of molecule libraries on patient-specific iPSC-based neuronal cells for drug repurposing. The initial phase of the study has identified four potential metrics to be used for the screening of EMA and FDA approved drugs (repurposing): [1] measurement of the mitochondrial membrane potential using fluorophores, [2] measurement of calcium transients using fluorophores and reporter constructs, [3] measurement of the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) using a Seahorse flux analyzer, and [4] investigation of the axonal outgrowth and branching patterns of the iPSC-derived neuronal cells by high-content screening. Compounds for which the investigators are able to confirm a positive effect by the above mentioned read-out methods will subsequently be provided to a selected number of patients for off-label compassionate use in cases where no standard treatment is available.
- Being tested
- skin biopsy, generation of iPSCs, blood drawing, off-label compassionate drug use
- Keywords
- mitochondrial disease, drug repurposing, Leigh syndrome, iPSC derived neural cells, off-label compassionate use, dopaminergic neurons, neuronal precursor cells, maternal inheritance, autosomal recessive inheritance, autosomal dominant inheritance, X-chromosomal recessive inheritance
- Medical subject headings
- Leigh Disease, Mitochondrial Diseases, Multiple Pterygium Syndrome, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
skin biopsyProcedure or surgery
Taking a punch skin biopsy of 3 mm diameter under local anesthesia and culturing skin fibroblasts from them.
generation of iPSCsOther
Using cultured skin fibroblasts of the patients, iPSCs will be generated according to standard procedures.
blood drawingDiagnostic test
Drawing blood from a peripheral vein for DNA and RNA isolation. The degree of heteroplasmy (mutation load) for the mtDNA mutation will be determined in the blood DNA.
off-label compassionate drug useDrug
In case the investigators identify a positive hit during drug repurposing with FDA and EMA approved substances, they will offer it as off-label compassionate use to patients for whom no standard treatment is available.
| Study group | Role | What they receive |
|---|---|---|
| Leigh Syndrome (Maternally Inherited, MILS) | Patients with Leigh syndrome carrying disease-causing mutations in their mtDNA. This subtype of Leigh syndrome is called Maternally Inherited Leigh Syndrome (MILS) Receives: Procedure: skin biopsy; Other: generation of iPSCs; Diagnostic Test: blood drawing; Drug: off-label compassionate drug use | |
| Leigh Syndrome (AR, AD, XR) | Patients with mitochondrial diseases that are caused by mutations in the nuclear DNA, which may be inherited in an autosomal recessive (AR), autosomal dominant (AD), or X-chromosomal recessive (XR) mode of inheritance. Receives: Procedure: skin biopsy; Other: generation of iPSCs; Diagnostic Test: blood drawing; Drug: off-label compassionate drug use |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of the increased mitochondrial membrane potential
The investigators will measure the mitochondrial membrane potential in Leigh patient iPSC-derived neural cells. If the membrane potential can be normalized, a drug will be considered a positive hit. The membrane potential will be determined indirectly by the fluorescence intensity measurement of a membrane potential sensitive dye (TMRM). The patients' fluorescence readings will be compared to the fluorescence readings of neural cells that have been generated from healthy control iPSCs.
Measured: 1 year
Secondary outcomes (2)
Reconstitution of the neural outgrowth pattern
The invesitgators will measure the neural axonal outgrowth and branching pattern in Leigh patient iPSC-derived neural cells using high content screening. If a normal outgrowth and branching pattern can be reconstituted in the patient iPSC-derived neural cells, a drug will be considered a positive hit. Axonal outgrowth and branching will be determined by high throughput parallel microscopy. This will determine the axonal growth velocity and the number of branch points per axon. Patients' data will be compared to healthy control iPSC-derived neural cells.
Measured: 1 year
Measuring calcium transients in iPSC derived neural cells
The investigators will measure calcium transients in Leigh patient iPSC-derived neural cells after electrical stimuation or after chmical stimulation using histamin. This essay will be used for high content screening. If a normal calcium signalling pattern can be reconstituted, a drug will be considered a positive hit. The mitochondrial calcium content will be determined using a fluorescent reporter construct (CEPIA) that is targeted into the mitochondrial matrix. No calibrated absolute measurements are possible. The calcium transients of the patient iPSC-derived neural cells will be compared to those of healthy control iPSC-derived neural cells.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2025
- Study start1 Mar 2020
- Primary completion28 Feb 2030 (estimated)
- Study completion28 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Leigh Syndrome (Maternally Inherited, MILS)Studies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- European Union, German Research Foundation, German Federal Ministry of Education and Research
- Responsible party
- Principal investigator, Markus Schuelke, M.D., Charite University, Berlin, Germany
- Investigators
- Markus Schuelke, MD, Principal investigator, CHARITE - UNIVERSITAETSMEDIZIN BERLIN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06967831
- Sponsor's protocol ID
- EA2_131_13
- Acronym
- cureMILS
- Status last verified
- May 2025
- First submitted
- 20 Apr 2025
- Last updated
- 13 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data can be shared upon reasonable request. A data accession committee will decide on each request.
Publications
Lorenz C, Lesimple P, Bukowiecki R, Zink A, Inak G, Mlody B, Singh M, Semtner M, Mah N, Aure K, Leong M, Zabiegalov O, Lyras EM, Pfiffer V, Fauler B, Eichhorst J, Wiesner B, Huebner N, Priller J, Mielke T, Meierhofer D, Izsvak Z, Meier JC, Bouillaud F, Adjaye J, Schuelke M, Wanker EE, Lombes A, Prigione A. Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders. Cell Stem Cell. 2017 May 4;20(5):659-674.e9. doi: 10.1016/j.stem.2016.12.013. Epub 2017 Jan 26.
PubMed 28132834Diodato D, Schiff M, Cohen BH, Bertini E, Rahman S; Workshop participants. 258th ENMC international workshop Leigh syndrome spectrum: genetic causes, natural history and preparing for clinical trials 25-27 March 2022, Hoofddorp, Amsterdam, The Netherlands. Neuromuscul Disord. 2023 Aug;33(8):700-709. doi: 10.1016/j.nmd.2023.06.002. Epub 2023 Jun 15. No abstract available.
PubMed 37541860Henke MT, Zink A, Diecke S, Prigione A, Schuelke M. Generation of two mother-child pairs of iPSCs from maternally inherited Leigh syndrome patients with m.8993 T > G and m.9176 T > G MT-ATP6 mutations. Stem Cell Res. 2023 Mar;67:103030. doi: 10.1016/j.scr.2023.103030. Epub 2023 Jan 17.
PubMed 36669241Steiner T, Zink A, Henke MT, Cecchetto G, Buenning M, Rossi A, Schuelke M, Prigione A. RNA-based generation of iPSCs from a boy carrying the mutation m.9185 T>C in the mitochondrial gene MT-ATP6 and from his healthy mother. Stem Cell Res. 2022 Oct;64:102920. doi: 10.1016/j.scr.2022.102920. Epub 2022 Sep 15.
PubMed 36137325Carli S, Levarlet A, Diodato D, Bertini ES, Martinelli D, Malandrini A, Lopergolo D, Gallus GN, Ganetzky RD, La Morgia C, Carelli V, Primiano G, Dominguez-Gonzalez C, Serrano-Lorenzo P, Martin MA, Ardissone A, Lamperti C, Nicoletta V, Klopstock T, Distelmaier F, Zeng L, Buchner B, Mancuso M, Schuelke M, Prigione A, Garone C. Natural History of Patients With Mitochondrial ATPase Deficiency Due to Pathogenic Variants of MT-ATP6 and MT-ATP8. Neurology. 2025 Apr;104(7):e213462. doi: 10.1212/WNL.0000000000213462. Epub 2025 Mar 20.
PubMed 40112238Inak G, Rybak-Wolf A, Lisowski P, Pentimalli TM, Juttner R, Glazar P, Uppal K, Bottani E, Brunetti D, Secker C, Zink A, Meierhofer D, Henke MT, Dey M, Ciptasari U, Mlody B, Hahn T, Berruezo-Llacuna M, Karaiskos N, Di Virgilio M, Mayr JA, Wortmann SB, Priller J, Gotthardt M, Jones DP, Mayatepek E, Stenzel W, Diecke S, Kuhn R, Wanker EE, Rajewsky N, Schuelke M, Prigione A. Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome. Nat Commun. 2021 Mar 26;12(1):1929. doi: 10.1038/s41467-021-22117-z.
PubMed 33771987
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using iPSC Derived Human Basal Ganglia Neurons From Patients With Leigh Syndrome for Metabolic Studies, Assay Development, and Drug Repurposing.
- ClinicalTrials.gov ID
- NCT06967831
- Acronym / sponsor ID
- cureMILS / EA2_131_13
- Keywords
- mitochondrial disease, drug repurposing, Leigh syndrome, iPSC derived neural cells, off-label compassionate use, dopaminergic neurons, neuronal precursor cells, maternal inheritance
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- European Union, German Research Foundation, German Federal Ministry of Education and Research
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 28 Feb 2030 (estimated)
- Study completion
- 28 Feb 2030 (estimated)
- First posted
- 13 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this project, the investigators are using iPSC lines derived from patients with Leigh syndrome that carry mutations in the mitochondrial (mtDNA) and in the nuclear DNA (nDNA) to reprogram them into neural progenitor cells and into dopaminergic neurons. The researchers are using this experimental system to screen FDA (Food and Drug Administration, USA) and EMA (European Medicines Agency) approved drugs for a positive effect on Leigh patient-derived neuronal cells (drug repurposing) using various biochemical, optic, and morphological outcome measures. Confirmed positive hits may be used for compassionate off-label use in Leigh patients when no standard treatment is available.
Detailed description
Leigh syndrome is a rare severe hereditary neurological disease that typically manifests during early childhood and is characterized by the progressive loss of motor and intellectual skills. A hallmark of the disease is the degeneration of neuronal cells in the brainstem and in the basal ganglia, particularly the dopaminergic neurons therein. The genetic underpinnings of this condition are multifaceted, encompassing mutations in both nuclear genes and in those contained within the mitochondrial DNA (mtDNA). The investigators hypothesize that these mutations share a common principle in their capacity to induce dysfunction of mitochondrial processes and of bioenergetic metabolism. The precise mechanism underlying neuronal death remains to be elucidated as researchers presently lack suitable disease models. Notably, the generation of a mouse model for mtDNA mutations has not been achieved, necessitating the exclusive reliance on patient derived material for research into the pathogenesis of these diseases. Moreover, there are currently no pathogenesis-based treatment approaches that have been demonstrated to improve patients' symptoms. Here, the investigators aim to utilize reprogramming technologies to engineer innovative human-derived disease models for research into Leigh syndrome. To this end, the investigators plan generating induced pluripotent stem cells (iPSCs) from fibroblasts of different Leigh syndrome patients who carry both nuclear (e.g. in SURF1) and mtDNA mutations (e.g. in MT-ATP6). Pluripotent progenitor cells offer a novel approach to better understand the pathogenesis of genetic diseases. In the case of Leigh syndrome, accessible cells, such as skin or blood cells, are almost never clinically affected. However, the nerve cells of the basal ganglia, which cannot be obtained via biopsies, are predominantly affected. The underlying mechanisms by which these dopaminergic neurons are particularly vulnerable to mitochondrial dysfunction and subsequent death remain to be elucidated. The objective of this study is to differentiate these induced pluripotent stem cells (iPSCs) into neural precursor cells (NPCs) and then into a neuronal cell population that is predominant inside the basal ganglia, such as dopaminergic neurons. Subsequently, a detailed analysis of these neurons will be conducted to ascertain mitochondrial and metabolic parameters, with the objective of elucidating neuronal changes associated with mitochondrial disease. Consequently, based on the identified dysfunction, imaging test procedures will be developed that are aimed at high sample throughput. This should enable high-throughput screening of molecule libraries on patient-specific iPSC-based neuronal cells for drug repurposing. The initial phase of the study has identified four potential metrics to be used for the screening of EMA and FDA approved drugs (repurposing): [1] measurement of the mitochondrial membrane potential using fluorophores, [2] measurement of calcium transients using fluorophores and reporter constructs, [3] measurement of the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) using a Seahorse flux analyzer, and [4] investigation of the axonal outgrowth and branching patterns of the iPSC-derived neuronal cells by high-content screening. Compounds for which the investigators are able to confirm a positive effect by the above mentioned read-out methods will subsequently be provided to a selected number of patients for off-label compassionate use in cases where no standard treatment is available.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Leigh Syndrome (Maternally Inherited, MILS) | – | Procedure: skin biopsy, Other: generation of iPSCs, Diagnostic Test: blood drawing, Drug: off-label compassionate drug usePatients with Leigh syndrome carrying disease-causing mutations in their mtDNA. This subtype of Leigh syndrome is called Maternally Inherited Leigh Syndrome (MILS) |
| Leigh Syndrome (AR, AD, XR) | – | Procedure: skin biopsy, Other: generation of iPSCs, Diagnostic Test: blood drawing, Drug: off-label compassionate drug usePatients with mitochondrial diseases that are caused by mutations in the nuclear DNA, which may be inherited in an autosomal recessive (AR), autosomal dominant (AD), or X-chromosomal recessive (XR) mode of inheritance. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients (male and female) who are affected by Leigh syndrome and carry a pathogenic mutation in a gene known to be associated with Leigh syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| skin biopsyTaking a punch skin biopsy of 3 mm diameter under local anesthesia and culturing skin fibroblasts from them. | Procedure or surgery | Leigh Syndrome (AR, AD, XR), Leigh Syndrome (Maternally Inherited, MILS) |
| generation of iPSCsUsing cultured skin fibroblasts of the patients, iPSCs will be generated according to standard procedures. | Other | Leigh Syndrome (AR, AD, XR), Leigh Syndrome (Maternally Inherited, MILS) |
| blood drawingDrawing blood from a peripheral vein for DNA and RNA isolation. The degree of heteroplasmy (mutation load) for the mtDNA mutation will be determined in the blood DNA. | Diagnostic test | Leigh Syndrome (AR, AD, XR), Leigh Syndrome (Maternally Inherited, MILS) |
| off-label compassionate drug useIn case the investigators identify a positive hit during drug repurposing with FDA and EMA approved substances, they will offer it as off-label compassionate use to patients for whom no standard treatment is available. | Drug | Leigh Syndrome (AR, AD, XR), Leigh Syndrome (Maternally Inherited, MILS) |
Primary outcome
Reduction of the increased mitochondrial membrane potential
Time frame: 1 year
The investigators will measure the mitochondrial membrane potential in Leigh patient iPSC-derived neural cells. If the membrane potential can be normalized, a drug will be considered a positive hit. The membrane potential will be determined indirectly by the fluorescence intensity measurement of a membrane potential sensitive dye (TMRM). The patients' fluorescence readings will be compared to the fluorescence readings of neural cells that have been generated from healthy control iPSCs.
2 secondary outcomes
Reconstitution of the neural outgrowth pattern
Time frame: 1 year
Measuring calcium transients in iPSC derived neural cells
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2025.
- Background: PubMed 28132834Lorenz C, Lesimple P, Bukowiecki R, Zink A, Inak G, Mlody B, Singh M, Semtner M, Mah N, Aure K, Leong M, Zabiegalov O, Lyras EM, Pfiffer V, Fauler B, Eichhorst J, Wiesner B, Huebner N, Priller J, Mielke T, Meierhofer D, Izsvak Z, Meier JC, Bouillaud F, Adjaye J, Schuelke M, Wanker EE, Lombes A, Prigione A. Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders. Cell Stem Cell. 2017 May 4;20(5):659-674.e9. doi: 10.1016/j.stem.2016.12.013. Epub 2017 Jan 26.
- Background: PubMed 37541860Diodato D, Schiff M, Cohen BH, Bertini E, Rahman S; Workshop participants. 258th ENMC international workshop Leigh syndrome spectrum: genetic causes, natural history and preparing for clinical trials 25-27 March 2022, Hoofddorp, Amsterdam, The Netherlands. Neuromuscul Disord. 2023 Aug;33(8):700-709. doi: 10.1016/j.nmd.2023.06.002. Epub 2023 Jun 15. No abstract available.
- Results publication: PubMed 36669241Henke MT, Zink A, Diecke S, Prigione A, Schuelke M. Generation of two mother-child pairs of iPSCs from maternally inherited Leigh syndrome patients with m.8993 T > G and m.9176 T > G MT-ATP6 mutations. Stem Cell Res. 2023 Mar;67:103030. doi: 10.1016/j.scr.2023.103030. Epub 2023 Jan 17.
- Results publication: PubMed 36137325Steiner T, Zink A, Henke MT, Cecchetto G, Buenning M, Rossi A, Schuelke M, Prigione A. RNA-based generation of iPSCs from a boy carrying the mutation m.9185 T>C in the mitochondrial gene MT-ATP6 and from his healthy mother. Stem Cell Res. 2022 Oct;64:102920. doi: 10.1016/j.scr.2022.102920. Epub 2022 Sep 15.
- Results publication: PubMed 40112238Carli S, Levarlet A, Diodato D, Bertini ES, Martinelli D, Malandrini A, Lopergolo D, Gallus GN, Ganetzky RD, La Morgia C, Carelli V, Primiano G, Dominguez-Gonzalez C, Serrano-Lorenzo P, Martin MA, Ardissone A, Lamperti C, Nicoletta V, Klopstock T, Distelmaier F, Zeng L, Buchner B, Mancuso M, Schuelke M, Prigione A, Garone C. Natural History of Patients With Mitochondrial ATPase Deficiency Due to Pathogenic Variants of MT-ATP6 and MT-ATP8. Neurology. 2025 Apr;104(7):e213462. doi: 10.1212/WNL.0000000000213462. Epub 2025 Mar 20.
- Results publication: PubMed 33771987Inak G, Rybak-Wolf A, Lisowski P, Pentimalli TM, Juttner R, Glazar P, Uppal K, Bottani E, Brunetti D, Secker C, Zink A, Meierhofer D, Henke MT, Dey M, Ciptasari U, Mlody B, Hahn T, Berruezo-Llacuna M, Karaiskos N, Di Virgilio M, Mayr JA, Wortmann SB, Priller J, Gotthardt M, Jones DP, Mayatepek E, Stenzel W, Diecke S, Kuhn R, Wanker EE, Rajewsky N, Schuelke M, Prigione A. Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome. Nat Commun. 2021 Mar 26;12(1):1929. doi: 10.1038/s41467-021-22117-z.
- Individual participant dataSharing planned: Undecided. Data can be shared upon reasonable request. A data accession committee will decide on each request.
Related trials for Leigh Syndrome (Maternally Inherited, MILS)
RecruitingObservational study
North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC)
Mitochondrial Disorders, Mitochondrial Genetic Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Markus Schuelke, MD principal investigator
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Leigh Syndrome (Maternally Inherited, MILS) and Leigh Syndrome (AR, AD, XR), run by Charite University, Berlin, Germany at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Markus Schuelke, MD (+49 30 4505 66112, markus.schuelke@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of the increased mitochondrial membrane potential (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06967831, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.