According to a report of the Berlin health portal "Gesundheitsstadt Berlin" (1), the neuro-pediatrician Professor Markus Schülke-Gerstenfeld, together with stem cell researchers and neurophysiologists at the Charité Berlin, has developed a disease model based on patients' own cells. For this purpose, body cells were first transformed into induced pluripotent stem cells (2) in order to develop neuronal cells of the central nervous system, on which the researchers could test potentially effective pharmaceuticals. During the screening, a drug that had already been approved for the treatment of another disease proved to be suitable. In the end, the treatment led to the patient being able to go back to school today.

The young man suffers from Leigh syndrome (LS) cardiomyopathy. The disease is caused by mutations in the complex IV assembly factor SURF1, which is one of the main causes of LS, a rare fatal neurological disease. Here, cells of the brainstem and basal ganglia region gradually die. A typical symptom is a slackening of the muscles - similar to amyotrophic lateral sclerosis (ALS). Children, who are born with a congenital genetic defect usually do not reach adulthood. To date, there is no treatment for rare hereditary mitochondrial disease. The young man was already paralyzed, had lost consciousness, and had to be artificially ventilated.

Animal experiments had not led to any treatment options in research. SURF1-deficient animals also could not recapitulate the neuronal pathology of human LS, resulting in no treatment options (3).

Therefore, the research team generated induced pluripotent stem cells from LS patients carrying homozygous SURF1 mutations. In a previous research work (3), the scientists have already shown that SURF1 mutations cause a failure in the development of mature neurons.

In Europe, a disease is considered rare if no more than five per 10,000 inhabitants are affected.
Worldwide, 300 million people live with a rare disease - with no prospect of a cure. Orphan diseases are extremely diverse and complex and have predominantly genetic causes. For those affected, this means lifelong health restrictions due to certain forms of cancer, diseases of the cardiovascular system, the nerves, the metabolism, or the immune system, with frequently a shortened life expectancy.

The basic principles and possible therapies of orphan diseases have so far mostly been researched using genetically modified mice. However, such animal models are also controversial in the scientific community because mice develop different symptoms than humans and they cannot replicate human metabolic responses to drugs due to species differences in genetics and physiology.  Individual differences among patients may also necessitate personalized medicine.

In recent years, countless tissue and organ modules have been developed in micro-physiological circulating systems, even with up to 13 organ-like systems. The combination of such tissues from the patient's own cells with integrated immune cells may provide a valuable means to explore the mechanisms of rare diseases (disease-on-a-chip).

Source:
(1) https://www.gesundheitsstadt-berlin.de/
(2) Inak-Girrbach, G. (2019).  Modeling Leigh syndrome using patient-specific induced pluripotent stem cells. Inaugural dissertation, Free University of Berlin. https://core.ac.uk/download/pdf/268939013.pdf
(3) Inak, G., Rybak-Wolf, A., Lisowski, P. et al. (2019).  SURF1 mutations causative of Leigh syndrome impair human neurogenesis. BioRxiv preprint
https://www.biorxiv.org/content/10.1101/551390v1