Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Neurology

Alzheimer's disease (AD)

Toll-like receptor 4 (TLR4)

Cell culture and mouse studies suggest moderately agonizing TLR4 could help treat AD. In cell culture, mouse microglia treated with the moderate TLR4 agonist monophosphoryl lipid A (MPL) had increased levels of proinflammatory activity and phagocytic behavior compared with negative controls treated with vehicle but had a decreased inflammatory response compared with positive controls treated with the strong TLR4 agonist lipopolysaccharide (LPS). In a mouse model of AD, intraperitoneal injection of MPL decreased b-amyloid (Ab) plaque levels in the brain compared with injection of vehicle or LPS and induced a modest proinflammatory response and stimulated blood monocyte activity. Next steps include optimizing MPL dosing and testing the compound in other mouse models of AD.
MPL is a component of Cervarix, a bivalent vaccine against HPV types 16 and 18 that is marketed by GlaxoSmithKline plc (see Toll-erating AD, page 6).

SciBX 6(4); doi:10.1038/scibx.2013.93
Published online Jan. 31, 2013

Patents on the use of MPL as an immunomodulatory agent held by GlaxoSmithKline; licensing status undisclosed

Michaud, J.-P. et al. Proc. Natl. Acad. Sci. USA; published online Jan. 15, 2013;
doi:10.1073/pnas.1215165110
Contact: Serge Rivest, Universite Laval, Quebec City, Quebec, Canada
e-mail:
serge.rivest@crchul.ulaval.ca

Contact: Daniel Larocque, GlaxoSmithKline Vaccines, Laval, Quebec, Canada
e-mail:
daniel.a.larocque@gsk.com