Klinische studie met iPS cellen voor de ziekte van Parkinson Clinical

Innovatie Attaché Tokio
Kugako Sugimoto, March 12 2014, meer informatie: www.ianetwerk.nl
Klinische studie met iPS cellen voor de ziekte van Parkinson
Clinical test with iPS cells for Parkinson’s disease
Samenvatting
Een onderzoeksgroep van de Kyoto University heeft een plan aangekondigd om in 2016 te
beginnen met klinische studies van de behandeling van de ziekte van Parkinson met
geïnduceerde pluripotente stamcellen. De behandeling start met het creëren van de iPS
cellen afkomstig van de patiënt. Vervolgens worden deze cellen geïnduceerd tot precurors
van dopamine gerelateerde neuronen. Deze precurors zullen daarna geïmplanteerd worden
in de hersenen van de patiënt In het protocol van de klinische studies zullen procedures
voor effectieve creatie van dopamine gerelateerde neuronprecursors en de nauwkeurige
selectie van deze precursors door het gebruik van Corin-antilichamen worden opgenomen.
Eerder zijn met goed resultaat studies van autologe transplantaties gedaan bij primaten met
een minimale immuunrespons. Deze klinische studies met mensen volgen op eerder door het
onderzoeksinstituut RIKEN aangekondigde plannen voor klinische studies van stamcellen
voor netvliesbehandelingen
Summary
A research team of Kyoto University announced a plan for a clinical study to treat Parkinson’s
disease by using iPS cells in 2016. Treatment starts with the creation of iPS cells from
patients followed by an induction into dopaminergic neuron precursors. Obtained
dopaminergic neuron precursors would be transplanted into the brain of the patients.
Effective culturing of dopaminergic neuron precursors by using synthetic laminins and
accurate selection of dopaminergic neuron precursors by using anti-Corin antibody will be
incorporated into the protocol for the clinical test. An animal study by using non-human
primate has been completed with good results of autologous transplantation with minimum
immune response. This clinical test would be the second human test following a study by
RIKEN in Japan on retinal regeneration.
Details
The research team of Kyoto University led by Prof. Jun Takahashi announced a plan to start
the clinical study how to treat Parkinson’s disease by using iPS cell technology in 2016
according to news from Kyoto University dated on March 7, 2014.
-----NOST Tokyo | Embassy of the Kingdom of the Netherlands
3-6-3 Shibakoen, Minato-ku, Tokyo 105-0011, Japan | T:+81-3-5776-5510 | F:+81-3-5776-5534 | [email protected]
Parkinson’s disease1 is caused by decrease of dopamine-generating2 cells in the central
nervous system. Symptoms are shaking, difficulty in walk, and others. The clinical onset of
the disease occurs mostly in older people beyond the age of 50. It affects about one in every
200 people worldwide. Currently, there is not a fundamental treatment for this disease,
though drugs to alleviate symptoms are available.
A transplantation test of dopaminergic neurons created from iPS cells to the brains in nonhuman primates has already been conducted.
In this study, iPS cells were created by the fibroblasts obtained from the oral mucosa of the
non-human primate by using retroviral vectors. Midbrain dopaminergic neurons were induced
from iPS cells by the addition of purmorphamine3, a molecule involved in bone growth and
brain development, and FGF8, a fibroblasts growth factor, followed by FGF2 and FGF20.
During the observation of the development into dopaminergic neurons, markers of
pluripotency (OCT44) decreased and markers for differentiated neurons, characteristic of
midbrain dopaminergic neurons such as LMX1A, FOXA2, TH, and TITX3, started to express.
Then, the suspension from the culture was prepared for the injection to one of the putamen5
of non-human primates. No immunosuppressant was used to compare the effect between
the autologous and allogeneic transplantation.
The immune response and survival of transplanted cells were observed for the recipient
primates of allografts and autografts for 3-4 months. Autografts caused a minimum immune
response in the recipient brains, while allografts might trigger immune response. Grafted
cells survived in both types of transplantation without immunosuppressant. The volume of
the developed dopaminergic neurons of two types of transplants did not show significant
differences. However, the number as dopaminergic neuron were higher in autografts than
allografts.
Based on the preliminary test on nonhuman primates, clinical trials to treat Parkinson’s
disease will use the patient’s own cells probably from the blood to create iPS cells for
autografts. The clinical test will be conducted at the Center for iPS Cell Research and
Application (CiRA) and Kyoto University Hospital including the observation of post
transplantation to secure safety of the technology. Goals of this test are to improve
symptoms and suppress the progression of the disease.
Osaka University and private companies also helped to establish a protocol for the clinical
trial to produce ample and high quality of dopaminergic neuron precursors. The team will use
synthetic laminin（recombinant laminin 511E8 fragments created by Osaka University）
instead of mouse-derived feeder cells for adherent culturing. Laminin is a protein to hold
cells together. Then, the cultured dopaminergic neuron precursors will be selected and
concentrated by the cell sorting machine. Dopaminergic neuron precursors that have corins
are picked up through the reaction with the fluorescence attached anti-Corin antibody in a
cell sorting machine. Unwanted cells that might cause tumors due to proliferative ability
would be excluded from the cultured grafts.
-----NOST Tokyo | Embassy of the Kingdom of the Netherlands
3-6-3 Shibakoen, Minato-ku, Tokyo 105-0011, Japan | T:+81-3-5776-5510 | F:+81-3-5776-5534 | [email protected]
Prior to conducting clinical test, several approvals are required. First, the research team will
submit the application to the third-party review panel (Certification Board) in Kyoto
University in 2015. Then, the team needs an additional approval from the Ministry of Health,
Labour and Welfare through the safety checks. Then the clinical test would start in 2016.
This trial would be the second clinical study using iPS cells in Japan. The first clinical study is
being conducted by the research team of RIKEN lead by Dr. Masayo Takahashi for
regeneration of retinas by iPS cells.
1.
2.
3.
4.
5.
Parkinson’s disease (Wikipedia)
dopamine (Wikipedia)
purmorphamine (Wikipedia)
OCT4 (Wikipedia)
putamen (Wikipedia)
Bronnen
Source
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2.
3.
4.
Asuka Morizane, et al., (2013) Stem Cell Reports (1) 283-292
Bao-Yang Hu, et al. (2010) PNAS (107) 9, 4335-4340)
News from Kyoto University
Yomiuri Online (Feb. 27, 2014), Parkinson’s disease treatment by iPS, clinical trial by
Kyoto University
Streamer
Kyoto University announced a plan of a clinical study to treat Parkinson’s disease by using
iPS cells in 2016.
-----NOST Tokyo | Embassy of the Kingdom of the Netherlands
3-6-3 Shibakoen, Minato-ku, Tokyo 105-0011, Japan | T:+81-3-5776-5510 | F:+81-3-5776-5534 | [email protected]