In your opinion, which is the biggest hurdle that might impede the development of AMPs as commercial therapeutic agents? How to overcome it?
Dear Naveen
I agree with Sezer, but there are also the a few other aspects that you need to consider when you have a lead peptide or derived compound:
- peptides are not orally available, so an oral formulation (hopefully a reality in the near future) must be part of the development;
- if it is for topical/aerosol application, formulation to retain activity must again be part of the development;
-it must have an in vivo activity/toxicity within the limits of a good antibiotic (mice models are a good start)
- if it is for systemic application pharmacokinetic, bio-availabiliy and distribution data are essential ( will it reach the target at high enough concentrations and stay around long enough to kill the pathogens);
- and finally cost and difficulty of producing you peptide or peptide-derived compound could make or break the final movement into Phase I clinical trials and to procure funding from the Pharmaceutical companies.
Gramicidin S and tyrothricin (tyrocidine and gramicidin complex) have been around for ages in topical treatments. Apart from daptomycin, no newly discovered AMP has made it yet onto the clinical market, specifically for systemic infections. However, there are a few in clinical trials, so there is hope that these amazing compounds will one day save lifes.
Hope it helps.
Regards
Marina
Dear Naveen
I agree with Sezer, but there are also the a few other aspects that you need to consider when you have a lead peptide or derived compound:
- peptides are not orally available, so an oral formulation (hopefully a reality in the near future) must be part of the development;
- if it is for topical/aerosol application, formulation to retain activity must again be part of the development;
-it must have an in vivo activity/toxicity within the limits of a good antibiotic (mice models are a good start)
- if it is for systemic application pharmacokinetic, bio-availabiliy and distribution data are essential ( will it reach the target at high enough concentrations and stay around long enough to kill the pathogens);
- and finally cost and difficulty of producing you peptide or peptide-derived compound could make or break the final movement into Phase I clinical trials and to procure funding from the Pharmaceutical companies.
Gramicidin S and tyrothricin (tyrocidine and gramicidin complex) have been around for ages in topical treatments. Apart from daptomycin, no newly discovered AMP has made it yet onto the clinical market, specifically for systemic infections. However, there are a few in clinical trials, so there is hope that these amazing compounds will one day save lifes.
Hope it helps.
Regards
Marina
Toxicity is a major hurdle
Explore SATPdb to find antimicrobial peptides which are non-toxic to normal cells
There are 8634 such peptides which are antimicrobial but not toxic
http://crdd.osdd.net/raghava/satpdb/search_advance_subb.php?field1=antimicrobial&operator1=NOT&field3=toxic&operator3=AND
SATPdb: A database of structurally annotated therapeutic peptides.
http://crdd.osdd.net/raghava/satpdb/
paper link
http://nar.oxfordjournals.org/content/early/2015/11/01/nar.gkv1114.full
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