Development of Drugs That Target Proteopathic Seeds Will Require Measurement of Drug Mechanism in Human Brain
- 750 Downloads
The notion that many neurodegenerative diseases are caused by seeded protein aggregation is almost 20 years old (Jarrett and Lansbury, Cell 73:1055–1058, 1993; Lansbury, Neuron 19:1151–1154, 1997). Recent data, some of it summarized here, suggest that this mechanism may account for cell-to-cell transmission throughout the brain by “proteopathic seeds.” There are many scientific questions that remain to be solved, including what is the best approach to interfere with the seeding process in vivo. But it may be more important to address the practical bottleneck that is common to all therapeutic strategies: how can one demonstrate potential efficacy of an experimental drug in a small, inexpensive clinical trial? This manuscript will address the issues that, together, have produced this bottleneck and will suggest some possible approaches to stimulate drug development for neurodegeneration.
KeywordsAmyloid Plaque Prion Disease Experimental Drug Gamma Secretase Inhibitor Amyloid Plaque Load
- DiMasi JA, Grabowski HG (2012) R&D costs and returns to new drug development: a review of the evidence. In: Danzon PM, Nicholson S (eds) Tufts Center for the Study of Drug Development. March/April CSDD Impact Report. The Oxford handbook of the economics of the biopharmaceutical industry. Oxford University Press, Oxford, pp 21–46Google Scholar
- Maarouf CL, Daugs ID, Kokjohn TA, Walker DG, Hunter JM, Kruchowsky JC, Woltjer R, Kaye J, Castaño EM, Sabbagh MN, Beach TG, Roher AE (2011) Alzheimer’s disease and non-demented high pathology control nonagenerians: comparing and contrasting the biochemistry of cognitively successful aging. PLoS One 6:e27291PubMedCrossRefGoogle Scholar
- Takeda press release (2011) http://www.takeda.com/press/article_39958.html