Recently I have become increasingly aware of an
emerging emphasis on using advances in biotechnology not just to cure disease
but to improve the capabilities of healthy people. This ‘human enhancement’
phenomenon is cropping up in all sorts of places ranging from the military
experimenting with ‘exoskeltons’ to give soldiers extra strength, to supposed
life-style enhancing ‘nutraceuticals’, to the first attempts to increase
longevity with drugs such as rapamycin. An interesting example was recently reported
in a NY Times Magazine article “Jump-Starter Kits for the Mind” (1). This
involved trans-cranial direct current stimulation (tCDS), a technique where
small currents are applied to regions of the brain to improve memory or
executive function. The idea is that the current stimulates neural tracts and
such ‘exercise’ increases function, thus reflecting the well-establish
neurobiological concept of Long Term Potentiation. As with it’s near relative, transcranial
magnetic stimulation (TMS), a number of studies in ageing patients with
impaired mental functions have claimed to detect benefits with use of tCDS.
This has prompted investigators to examine the effects of tDCS in healthy
people and, as described in the Times article, some positive results have been
found. Apparently, since the technology is so simple, this has also prompted
handy do-it-yourselfers to download how-to videos from YouTube and make tCDS
devices for themselves. Since there have not yet been large-scale, blinded,
controlled trials of tCDS or TMS the jury is still out on whether they really
work. However, the enthusiasm with which they have been adopted by scientists
and by some members of the public illustrate that there is tremendous interest
in in the whole human enhancement thrust.
Friday, November 22, 2013
Friday, November 15, 2013
FDA Doesn’t Make Sense Dealing With an Antisense Medication for Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD) is every parent’s
nightmare. It’s an X-chromosome linked genetic disease that condemns young boys
to paralysis and premature death. At present no therapy is available. However,
recent research has indicated that certain types of antisense oligonucleotides
can partially correct the genetic defect and at least slow the course of the
disease. A small-scale clinical trial of an antisense molecule called Eteplirsen was recently completed by the biotech company
Sarepta. The trial involved only twelve boys, but showed encouraging results.
Sarepta then asked the FDA for ‘accelerated approval’ of the drug. This is a relatively new mechanism whereby
the FDA can conditionally approve new drugs for which there is a major unmet
need, such as is the case in DMD. If the drug fails in subsequent larger-scale
trials it would then lose approval. However, the FDA declined and has insisted
on a full-scale placebo controlled trial of Eteplirsen prior to approval (1).
These decisions are always difficult. Clearly it is
the duty of the FDA to make sure that approved medications actually work and
are not a threat because of toxicity. However, stringent requirements for
‘classic’ clinical trials can keep good drugs out of the hands of needy patients
for years. Similar situations have cropped up in the cancer therapy area where
patients have pleaded for promising new drugs before these agents had completed
formal clinical trials (2).
There is a lot of interest currently in adaptive
clinical trials where advanced Bayesian statistics can be used to modulate
trial design as information is accrued, rather than to be stuck with a rigid
trial framework based on initial assumptions. One would think that the
‘accelerated approval’ process could be linked to trials of that type.
In this case it seems that FDA unnecessarily erred on
the side of caution. While it is important to protect patients against possible
toxicities of new drugs, in the case of Eteplirsen there was no evidence of
toxic effects among the boys treated. Thus it seems likely that little harm
would be done by letting additional patients be treated while more was being
learned about the drug.
(1)
(2)
Friday, November 8, 2013
Faith and Skepticism in Nanomedicine
As one who has intermittently
toiled in the field of nanoparticle mediated drug delivery, I am bemused by the
uncritical, almost reverent acceptance by the news media of each new
publication on nanomedicine that appears in a decent scientific journal. A couple of recent examples might include a
post on the Economist Babbage site enthusing about peptide-coated nanoworms
that are designed to detect elevations of protease activities in certain
disease states by releasing the peptides for detection in the urine. Another on
the CEN website lauds work using drug bearing polymers to suppress inflammation
in CNS microglial cells. This is not to criticize the scientists who did the
work or the studies themselves; they are certainly interesting science.
However, as is often the case in the nanomedicine area, these very early stage
investigations are hailed as breakthroughs that will inevitably result in
important advances in clinical medicine. Not likely!
Over the years I have seen
hundreds of novel and interesting strategies involving use of nanotechnology
for diagnosis or therapy come crashing to a halt as they encounter the
complexities of real-world medicine. Yet the breathless, awestruck acceptance
of new developments in this field continues. Apparently there is a robust mythology
about nanomedicine that is widely accepted. However, a bit more skepticism
would probably be good for the field in the long run.
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