Modelling Huntington's Disease using iPSCs and CRISPR/Cas9

Ioanna Kaklamanou, Monika Tsotsorou, Naverawaheed Arshad, Zahira Faizzad, Kennie Lind Rothmann & Fahmo Dahir Ali

Studenteropgave: Fagmodulprojekt


Huntington’s disease is a detrimental neurodegenerative disease that affects thousands of
people globally. The disease ultimately leads to death, usually in less than 20 years after the
onset of the symptoms. The genetic cause of the disease is a mutation that leads to an elongated
chain of the amino acid glutamine, increasing the length of the normal huntingtin protein. This
mutated protein aggregates inside the cells of the patients, leading to a wide variety of
symptoms. However, the way that the aggregation leads to neurodegeneration has not been
fully understood, with many scientists disagreeing about the exact mechanisms of the disease
progression. Something that has dramatically changed the way we see and study disorders, and
their causative mutations is disease modelling, either done in vivo or in vitro. Currently there
is no cure for Huntington’s disease, making research into possible treatments an important field
of study. An innovative approach considered was the use of embryonic stem cells that can
differentiate into any kind of cell. This approach was advanced further by the discovery of
somatic cells that can be reprogrammed into stem cells with the same characteristics as
embryonic stem cells, called induced pluripotent stem cells. These cells can even be
differentiated into medium spiny neurons, which are the cells predominantly affected by
Huntington’s disease. Induced pluripotent stem cells can be genetically modified to improve
the research of the disease, as isogenic models can be created by inducing or removing the
mutation from a cell line. The last few years, genome editing methods such as CRISPR have
made it possible to correct harmful mutations in the hope of curing a disease. In this report, our
aim is to discuss the possibility of studying Huntington’s disease with these novel methods,
while describing some of the latest discoveries that could affect the lives of patients. However,
many issues remain before stem cell disease modelling can answer all our questions about the
pathology of diseases and lead to cures for many diseases, including Huntington’s disease.

UddannelserBasis - Naturvidenskabelig Bacheloruddannelse, (Bachelor uddannelse) Basis
Udgivelsesdato18 dec. 2017
Antal sider39
VejledereCaroline Amalie Brunbjerg Hey