Bernard,
This is interesting – thanks for bringing it to my attention. I’m forwarding this abstract to my colleagues for our collective consideration.

One comment I would have at this point is that generally there is a significant and recognized problem in going from observations in a cell culture model to conclusions in an animal or human body. The way cells and tissues behave and react under conditions called ‘in vitro’ (coming from the Latin word for glass – i.e. in test tubes and such) can be vastly different from ‘in situ’ (again, a Latin derived phrase in this case referring to the normal cellular environment inside the body). The challenge to scientists is to not only do the experiments but to extrapolate as to how the results represent what occurs where we really care: in the body of a patient.

A previous example in ALS research is the identification of beta-lactams as influencing the glutamate transporter activity in a tissue culture system. The current clinical trial of Ceftriaxone is the immediate outcome of the previous tissue culture research and will ultimately determine any ‘in situ’ efficacy. Note that the results from TDF are that Ceftriaxone had no effect in the G93A SOD1 mouse. The researchers advocating and testing Ceftriaxone have, however, more than the significant hurdle to surmount of translating an activity observed ‘in silico’ to efficacy ‘in situ’. There is an additional fundamental question of whether glutamate excitotoxicity has any relevance whatsoever in ALS.

Links relating to Ceftriaxone and ALS:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15635412&query_hl=21&itool=pubmed_docsum

http://www.als.net/research/treatments/treatmentDetail.asp?studyType=internal&treatmentId=134


John McCarty, PhD
Treatment Investigator,
ALS Therapy Development Foundation

---

John McCarty, PhD
Director of Therapeutic Investigation
ALS Therapy Development Institute