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Biotech / Medical : Guilford (GLFD) - Steadily Rising
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To: Dr. John M. de Castro who wrote (386)8/14/2000 8:51:01 AM
From: scott_jiminez   of 496
 
John - great job in finding those abstracts.

While I think it's important we've cast some doubt on some of Guilford's explicit or implicit claims for NIL-A, it's too early to completely discount a potential use for NIL-A in PD.

There are countless thousands of papers on these topics (a PubMed search found ~4500 papers on 'FK506 or FKBP', ~800 on 'immunophilin', and ~5800 on 'OHDA or MPTP') and it can be dangerous and misleading to choose a few abstracts without the requisite current knowledge of the state of the field. This is not intended as criticism as much as caution - self directed as well since my (dated) knowledge of NGF may not be a completely appropriate basis to judge NIL-A. While the papers you cited appear to be quite damning for the overall value of NIL-A for PD, I think a better understanding of the entire immunophilin biology would be prudent to accurately assess NIL-A's prospects.

With that premise, my comments on the abstracts (with the undermining premise that deriving meaningful substance from an abstract is like reading Cliff's Notes for the bible)...

1. Winter et al. - My first reaction was axotomy is not a good model for PD. My second reaction was (if I ignore the first caveat) this head-to-head comparison shows NIL-A lacking the precise properties, UNDER THESE CIRCUMSTANCES, that would make it a breakthrough molecule for PD. Perhaps it is precisely the non-immuno-suppressive properties of NIL-A that are so widely touted that restrict its ability to be effective (but the Costantini et al. abstract [#3] would suggest otherwise) .

2. Harper et al. - You were to correct to draw conclusions from the amphetamine data. In addition, the experiment that most closely parallels PD (treating with GPI-1046 starting 1 month AFTER the 6-OHDA lesion), showed no effects in the nigral DA population whatsoever. Taking into account all the cautionary statements I've given, this is a 'disconcerting' result.

3. Costantini et al. - I guess this shows the general concept to be valid. Unfortunately for GLFD, NIL-A does not appear to have the same properties as V-10,367.

Here are the abstracts from the 'original' papers where the PD/NIL-A association may have been launched:

1. ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9050897&dopt=Abstract

2. ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9095176&dopt=Abstract

-Scott
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