eRapport

Developing precision medicine for patients with mitochondrial disorders

Prosjekt
Prosjektnummer
F-12135
Ansvarlig person
Omar Hikmat
Institusjon
Helse Bergen HF
Prosjektkategori
Postdoktorstipend
Helsekategori
Congenital Disorders, Neurological
Forskningsaktivitet
4. Detection and Diagnosis, 6. Treatment Evaluation
Rapporter
2024
Mitochondrial diseases are a group of genetic conditions that share in common impaired energy production. Mutations in POLG are the commonest cause of mitochondrial disease and are associated with a spectrum of clinical features ranging from devastating fatal early onset disease to mild late onset disease with myopathy.In order to study POLG disease, we established the National POLG registry which runs from Bergen and collaboration with colleagues in Sweden, Finland, Denmark, Netherlands, United Kingdom, Spain and Australia to assemble the largest international cohort of POLG patients. During the last year two new centers (Portugal and USA) joinrd our registry. This project addresses the following important areas: - Genotype-phenotype correlation, i.e. why the same mutation gives different phenotypes? - What biological and environmental events trigger the disease, particularly the catastrophic episodes of epileptic encephalopathy that are usually fatal? - What impact POLG disease has on maternal health? We have now recruited new patients to our POLG registry both from Norwegian and international centres, currently approaching more than 300 cases in our international cohort. This will improve the power of our studies. Patients recruiting is a continually process. This large and unique cohort enables us to perform our studies and come with robust and important findings. We have already published many important findings, especially the last year (please refer to research-production section), and are now in the final stage of this project.
2023
Mitochondrial diseases are a group of genetic conditions that share in common impaired energy production. Mutations in POLG are the commonest cause of mitochondrial disease and are associated with a spectrum of clinical features ranging from devastating fatal early onset disease to mild late onset disease with myopathy.In order to study POLG disease, we established the National POLG registry which is run from Bergen, and collaboration with colleagues in Sweden, Finland, Denmark, Netherlands, United Kingdom, and Spain to assemble the largest international cohort of POLG patients. During the last year, two new centers joined our registry including Sydney-Australia. This project addresses the following important areas: - Genotype-phenotype correlation, i.e. why the same mutation gives different phenotypes? - What biological and environmental events trigger the disease, particularly the catastrophic episodes of epileptic encephalopathy that are usually fatal? - What impact POLG disease has on maternal health? We have now recruited new patients to our POLG registry both from Norwegian and international centres, and we are approaching 220 cases in our international cohort, this will improve the power of our studies. Patients recruiting is a continually process. We have already started data analysis and will shortly publish the results of the following studies: Status epilepticus in patients with POLG disease and epidemiology of POLG disease in Norway.
2022
Mitochondrial diseases are a group of genetic conditions that share in common impaired energy production. Mutations in POLG are the commonest cause of mitochondrial disease and are associated with a spectrum of clinical features ranging from devastating fatal early onset disease to mild late onset disease with myopathy.In order to study POLG disease, we established the National POLG registry which is run from Bergen and collaboration with colleagues in Sweden, Finland, Denmark, Netherlands, United Kingdom and Spain to assemble the largest international cohort of POLG patients. This project addresses the following important areas: - Genotype-phenotype correlation, i.e. why the same mutation gives different phenotypes? - What biological and environmental events trigger the disease, particularly the catastrophic episodes of epileptic encephalopathy that are usually fatal? - What impact POLG disease has on maternal health? - Lastly the development of rational treatments. We will investigate the use of nicotinamide riboside (NR). Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for complex I of the respiratory chain, the mitochondrial pathway that generates ATP, and NR is a precursor of this compound. We hypothesize that oral administration of NR will improve neuronal NAD+ deficiency and lead to improved mitochondrial function and in turn will improve the clinical state and slow disease progression. We have now recruited new patients to our POLG registry both from Norwegian and international centres, and we are approaching more than 200 cases in our international cohort, this will improve the power of our studies. Patients recruiting is a continually process. We have already started data analysis and the results of the first two studies will shortly be published. We are also setting up NR-POLG trial procedures.
2021
Mitochondrial diseases are a group of genetic conditions that share in common impaired energy production. Mutations in POLG are the commonest cause of mitochondrial disease and are associated with a spectrum of clinical features ranging from devastating fatal early onset disease to mild late onset disease with myopathy.In order to study POLG disease, we established the National Norwegian POLG Registry which is run from Bergen and collaboration with colleagues in Sweden, Finland, Denmark, Netherlands, United Kingdom and Spain to assemble the largest international cohort of POLG patients. This project addresses the following important areas: - Genotype-phenotype correlation, i.e. why the same mutation gives different phenotypes? - What biological and environmental events trigger the disease, particularly the catastrophic episodes of epileptic encephalopathy that are usually fatal? - What impact POLG disease has on maternal health? - Lastly the development of rational treatments. We will investigate the use of nicotinamide riboside (NR). Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for complex I of the respiratory chain, the mitochondrial pathway that generates ATP, and NR is a precursor of this compound. We hypothesize that oral administration of NR will improve neuronal NAD+ deficiency and lead to improved mitochondrial function and in turn will improve the clinical state and slow disease progression. To increase the power of our studies, we are currently recruiting new patients to our POLG registry both from Norwegian and international centres, and will shortly start with data analysis. We are also setting up NR-POLG trial procedures.
Vitenskapelige artikler
Hikmat O, Naess K, Engvall M, Klingenberg C, Rasmussen M, Brodtkorb E, Ostergaard E, de Coo I, Pias-Peleteiro L, Isohanni P, Uusimaa J, Majamaa K, KäRppä M, Ortigoza-Escobar JD, Tangeraas T, Berland S, Harrison E, Biggs H, Horvath R, Darin N, Rahman S, Bindoff LA

Status epilepticus in POLG disease: a large multinational study.

J Neurol 2024 Aug;271(8):5156. Epub 2024 jun 1

PMID: 38822839

Mancuso M, Papadopoulou MT, Ng YS, Ardissone A, Bellusci M, Bertini E, Di Vito L, Evangelista T, Fons C, Hikmat O, Horvath R, Klopstock T, Kornblum C, Lamperti C, Licchetta L, Molnar MJ, Varhaug KN, O'Callaghan M, Pressler RM, Schiff M, Servidei S, Szabo N, Gorman GS, Cross JH, Rahman S

Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group.

Eur J Neurol 2024 Jul;31(7):e16275. Epub 2024 apr 4

PMID: 38576261

Hepsø SW, Lee M, Noszka K, Wollertsen YM, Holmaas G, Kristensen E, Eichele T, Bjork MH, Griffiths ST, Hikmat O

Refractory and super-refractory status epilepticus in children and adolescents: A population-based study.

Seizure 2024 Aug;120():116. Epub 2024 jun 24

PMID: 38941802

Kristensen E, Mathisen L, Berland S, Klingenberg C, Brodtkorb E, Rasmussen M, Tangeraas T, Bliksrud YT, Rahman S, Bindoff LA, Hikmat O

Epidemiology and natural history of POLG disease in Norway: a nationwide cohort study.

Ann Clin Transl Neurol 2024 Jul;11(7):1819. Epub 2024 jun 7

PMID: 38845467

Björkman K, Vissing J, Østergaard E, Bindoff LA, de Coo IFM, Engvall M, Hikmat O, Isohanni P, Kollberg G, Lindberg C, Majamaa K, Naess K, Uusimaa J, Tulinius M, Darin N

Phenotypic spectrum and clinical course of single large-scale mitochondrial DNA deletion disease in the paediatric population: a multicentre study.

J Med Genet 2023 Jan;60(1):65. Epub 2021 des 6

PMID: 34872991

Varhaug KN, Hikmat O, Bindoff LA

[Mitochondrial disease caused by the m.3243A>G mutation].

Tidsskr Nor Laegeforen 2022 Jun 28;142(10). Epub 2022 jun 27

PMID: 35763848

Parasyri M, Brandström P, Uusimaa J, Ostergaard E, Hikmat O, Isohanni P, Naess K, de Coo IFM, Nascimento Osorio A, Nuutinen M, Lindberg C, Bindoff LA, Tulinius M, Darin N, Sofou K

Renal Phenotype in Mitochondrial Diseases: A Multicenter Study.

Kidney Dis (Basel) 2022 Mar;8(2):148. Epub 2022 jan 24

PMID: 35527992

Hikmat O, Isohanni P, Keshavan N, Ferla MP, Fassone E, Abbott MA, Bellusci M, Darin N, Dimmock D, Ghezzi D, Houlden H, Invernizzi F, Kamarus Jaman NB, Kurian MA, Morava E, Naess K, Ortigoza-Escobar JD, Parikh S, Pennisi A, Barcia G, Tylleskär KB, Brackman D, Wortmann SB, Taylor JC, Bindoff LA, Fellman V, Rahman S

Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease.

Ann Clin Transl Neurol 2021 11;8(11):2155-2165. Epub 2021 okt 18

PMID: 34662929

Deltagere
  • Juan Darío Ortigoza-Escobar Prosjektdeltaker
  • Mikko Karrpa Prosjektdeltaker
  • Rita Horvath Prosjektdeltaker
  • de Coo Irenaeus Prosjektdeltaker
  • Elsebet Ostergaard Prosjektdeltaker
  • Niklas Darin Prosjektdeltaker
  • Martin Engvall Prosjektdeltaker
  • Karin Naess Prosjektdeltaker
  • Shamima Rahman Prosjektdeltaker
  • Anne Hansen Brukerrepresentant
  • Trine Tangeraas Prosjektdeltaker
  • Claus Klingenberg Prosjektdeltaker
  • Jörg Assmus Prosjektdeltaker
  • Espen Lien Prosjektdeltaker
  • Dag Moster Prosjektdeltaker
  • Kristin Nielsen Varhaug Prosjektdeltaker
  • Camilla Tøndel Prosjektdeltaker
  • Charalampos Tzoulis Prosjektdeltaker
  • Laurence Bindoff Prosjektdeltaker
  • Omar Hikmat Prosjektleder

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

Alle henvendelser rettes til Faglig rapportering, Helse Vest

Personvern  -  Informasjonskapsler