Comments on Reports of a “New Down Syndrome Therapy”

By Dr. Michael Harpold
Chief Scientific Officer, LuMind RDS Foundation

Many of you have asked about a recent news piece and associated press release entitled “New Down syndrome Therapy Discovered.” Although this is not a research endeavor LuMind RDS is funding, the following perspective is provided which may be helpful in addressing some questions and further understanding the underlying research study and its potential as described in a scientific journal and associated press release.

First, I’d like to point out that, in my view, the title of the press release is misleading and factually inaccurate regarding the underlying research and results. As we all know, often press release titles represent an attempt to draw in readers with a few succinct words, but frequently over-hypes the underlying story. At this point, neither the body of the press release nor the underlying scientific publication demonstrate the research or results as any actual near-term or potential therapy. Application as a possible therapy or therapeutic approach in individuals with Down syndrome, if any, would likely be quite limited and many years into the future and require extensive additional research.

The following represents a brief scientific perspective on the study, as recently published in the scientific literature:

  • The researchers describe an approach for introducing a gene, designated ZSCAN4 (a gene located on human chromosome 19) or a laboratory-modified form of its RNA product into (and resulting expression of the ZSCAN4 protein in) either mouse embryonic stem cells (which have abnormal numbers of chromosomes generated during cell culture maintenance and growth in the laboratory, but not derived from any mouse model for Ds) or human Trisomy 21 fibroblast cells, all maintained and grown in the laboratory in Petri dishes, i.e., in vitro cell culture, meaning not in a living laboratory animal or human.
    • The scientific data indicate that the approach results in loss of the extra chromosome(s) in a limited proportion of the cells grown in culture in the laboratory. Although the researchers state that the approach is “highly efficient” in reducing extra chromosomes in the cells, the actual results demonstrate that, while a significant change, it is arguably still a relatively low percentage. For any potential therapeutic application in humans the efficiency would likely be required to be very much higher and technically quite challenging and difficult to control.
    • It should also be noted that the actual biological function(s) of ZSCAN4 remains unclear and under continuing scientific investigation, although some other previous research results suggest it may be involved in certain chromosome and/or cell maintenance functions.
  • The published scientific study does not describe the application of the approach to a living laboratory animal, so it is impossible to assess or determine whether there would be any effect (therapeutic, side effects or otherwise), positive or negative, in a whole organism (laboratory animal or human) which would represent a potential therapy. Demonstration of potential therapeutic benefit/efficacy, and lack of any problematic side-effects, in a living laboratory animal model will be required for this approach to be considered a realistic potential therapy.
    • There will be significant technical challenges in potential application to a whole lab animal model, much less humans, and it is further quite challenging to imagine in the foreseeable future how the approach could potentially address treatment/improvement of cognitive function, including Alzheimer’s disease, in the brain in a person with Ds.
    • Given that the described approach results in loss of extra chromosomes at least in some cells grown in culture outside the body, it is possible to conceive that it might potentially be applied to “auto”-transplantation-type therapies (transfer of the treated animal’s own cells back into the animal) that might address certain blood or immune disorders, but not extend to any other organ systems or cells in the body. However, this will require considerable additional research to demonstrate such potential.

Overall, the scientific research is interesting and otherwise could lead to further insights on chromosomal or cell maintenance and functions generally as well as in Ds. This is a research area among a very broad range of other areas that will continue to be monitored. However at this stage, this research study and associated approach would not represent a  research area closely relevant to further understanding cognition or development of an associated practical cognitive or Alzheimer’s therapeutic in Ds.

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