It was then back to the science. Prof Frank Soldner (Massachusetts Institute of Technology) provided an overview of a new and exciting way in which MND-causing genes can be introduced into human embryonic stem cells in order to study the disease. Traditional gene transfection techniques are rather uncontrolled, resulting in multiple copies of the gene being introduced in random parts of the human genome – both of which can affect normal cellular functioning. A new genome-editing technique allows the existing ‘normal’ gene within the stem cells to be converted directly into a ‘mutant’ gene, which should result in the creation of stem cell-derived motor neurones that are much more representative of those in the patient.
Of course, the other way of getting to this point is not to use embryonic stem cells, but instead to use induced pleuripotent stem (iPS) cells, generated from skin samples taken from inherited ALS patients with a known gene mutation. Prof Jeff Rothstein (Johns Hopkins University) provided an update on the US National ALS Cell Bank which to date has produced 30 iPS cell lines from patients with various known MND gene mutations. He stressed the need for a large number of well characterised cells to be made available to the research community, as each one will be slightly different, putting it very succinctly with the statement: “You need more than one ‘human’ to test a hypothesis or a compound.”
The National ALS Cell Bank will create both motor neurones and a type of neurone support cell called ‘astrocytes’ from each iPS cell line.
We know very little about the different subtypes of astrocytes that are present in the central nervous system – we know that brain astrocytes are different from those in the spinal cord. Both Prof Rothstein and Prof Su-Chun Zhang (University of Wisconsin) highlighted recent research showing that there are marked ‘regional differences’ within the spinal cord itself.
Using different ‘cues’ Prof Zhang is able to develop subtypes of astrocytes similar to those found in different parts of the spinal cord. This information may be very important in understanding why the disease progresses so differently between one person and the next. As the emerging stem cell trials in MND are based on replacing and improving the astrocyte populations in the spinal cord, it is also likely to be important in maximising the chances of success in altering disease progression, by ensuring the stem cells turn into the right type of astrocyte, best able to support motor neurones around the site of injection.