Stem Cell Pilot Study

Posted - September 2009 in HSPRF News

Excellent Progress

Differences between HSP cell lines and non-HSP cell lines are both dramatic and consistent

The scientists have much of the information they need to set specific targets for therapeutic drug screening

by Robin Bligh, HSPRF President

Well over a year ago, we decided to collaborate with the NCASCR (National Centre for Adult Stem Cell Research within Griffith University in Qld.). The fact that they have direct reference to “also providing support for neglected diseases” in their Charter and they use non-controversial adult stem cells, did influence our decision, but so did our assessed scope of their capabilities relevant to our needs.

We agreed with the need to have a 12 month Pilot Study to find out whether the method would work with HSP, to learn more about the genes involved and cell changes due to the causal gene mutation. “Better to be sure the car’s engine is working before setting off” rather than launch in to a 5 year program without the experience. We raised the $100,000 and NCASCR (which has its Sydney node in the Department of Neurogenetics in the Kolling Institute of the University of Sydney) got started in early 2009.

The strength of the desire for research towards a cure was underlined when, after we advised people of the Pilot Study and the need for nasal biopsies, 42 people made contact with the Kolling Institute, leading to 40 blood samples being taken to test for SPG4. 25 people were eventually recruited for biopsies even though only 10 were required, the thinking being to gather samples while you can. The response to limited publicity from the HSP community was indeed encouraging.

The “car engine” seems to be more powerful than expected. This is what the NCASCR scientists can now say:

  1. A bank of 25 adult stem cell samples involving a variety of genes and mutations that can be called upon to study HSP is established.
  2. Disease specific alterations can be identified thus enabling the identification of therapeutic drug targets. (No conclusions are being drawn from drosophila or mice models of HSP. The models we are using are based on us humans!)
  3. Differences between all the HSP SPG4 cell lines and non-HSP (normal) cell lines in terms of the type and quantity of protein they trigger are both dramatic and consistent.
  4. The type and quantity of protein triggered by 6,100 genes in HSP SPG4 cell lines is significantly altered compared with normal cells.

What this means is that SPG4 is ‘recruiting’ 6,100 other genes to help cause damage and the scientists are ‘drilling down’ to the actual differences. So the scientists have much of the information they need to set specific targets for therapeutic drug screening, i.e. running thousands of potential drugs past the targets to detect those that can repair the damage and restore normal cell function.

The cell lines of human HSP SPG4 used in the Pilot Study are now proven to be effective cell models of HSP by showing changes in SPG4 mutated cells that are expected from both known and postulated functions of SPG4. This allows disease-causing alterations in cell biology to be revealed by comparing stem cell lines from multiple cases.