Friday, January 24, 2014

Academic Drug Discovery- Making it into the Big Time

A couple of years ago a survey of academic drug discovery in the US  (1) highlighted the fact that most of these efforts were at a very early stage of development. However, things have progressed. An interesting article in C&EN (2) presents the history of the drug discovery unit at Vanderbilt, one of the oldest and most successful of the academic ventures. It nicely shows how patient work at the basic level, rather than a rush to ‘translation” can eventually bear fruit. In this case it takes the form of AstraZeneca licensing the academic center’s work on small molecules for brain disorders such as schizophrenia.
The recent formation of an alliance of academic discovery groups should further facilitate progress (3 ). 

(1)  Frye S, Crosby M, Edwards T, Juliano R. (2011) US Academic Drug Discovery. Nat Rev Drug Discov. 10(6):409-10 



siRNA Hits The Jackpot!

Modulation of gene expression with siRNA has thus far failed to live up to its potential for therapeutics. After early work created great excitement and lured several major pharmaceutical companies to enter the field, by 2010 there was a mass exodus as the many problems with these complex molecules became apparent.  A few diehards persisted, particularly the biotech company Alnylam in Cambridge, MA.

 Now Alnylam has been rewarded for its persistence with a $700M investment from Sanofi. This focuses on Alnylam’s promising work in treatment of transthyrein-familial amyloid polyneuropathy, an important orphan disease.

One of the major problems with siRNA was the inability to effectively deliver these molecules to their intracellular targets. One approach to this has been to load the siRNA into cationic lipid nanoparticles. However, this often resulted in considerable toxicity. Recently Alnylam, as well as several academic labs, have been making ligand-siRNA conjugates that promote siRNA uptake by receptor- mediated endocytosis. An advantage of this approach is that ligand-siRNA conjugates are chemically defined molecules, unlike complex, multi-component nanoparticles.  However, the jury is still out on the therapeutic viability of this approach.

Friday, January 17, 2014

The FDA, 23andMe and the Precautionary Principle

As reported in this week’s NATURE the FDA recently ordered the genetic testing company 23and me to cease providing information about potential genetic risks to health. The FDA was essentially following the precautionary principle, citing that consumers might misinterpret such information leading to possible harm. This decision has been criticized by stating that such tests, as well as other non-physician provided health information, will ‘democratize’ health care. I think this is nonsense.

The FDA did exactly the right thing with regard to direct provision of genetic information to consumers.  Most people do not have sufficient knowledge of medical science to rationally interpret genetic testing and could potentially do themselves harm. The proponents of ready access to such testing use exactly the same ‘free market’ rationale here as in their arguments that oppose government-backed health plans in favor of a purely private health system. They ignore the fact that a free market in the health arena is essentially ‘inefficient’ since consumers to do have access to full information about services provided, costs, and consequences.