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dream of targeting DNA itself, first crudely and non-
selectively with drugs that intercalated with or broke down
DNA, but later more selectively at specific nucleotide
sequences with short chains of nucleotides
(oligonucleotides or oligos) (19,20). The road for oligos
from the laboratory to the bedside has been a long and
hard one but recent successes in the form of both licensed
medicines (see below) and promising clinical reports
suggest that the future may indeed been bright.
New therapies
From the greater insight into the phenomena which we
have mentioned have emerged a whole host of new
therapies that even Pasteur and Koch would have
wondered at.
(i) Small molecule targeted agents such as
imatinib and gefitinib which have
revolutionised the therapy of some cancers
21).
(ii) Macromolecular agents such as tacrolimus
which make possible long-term engraftment
of organs sometimes using age-old
approaches (22).
(iii) Exquisitely specific antibodies that tame
severe arthritis and skin diseases as well as comprehensive knowledge of drugs, their actions and use;
various cancers.
(iv) Epigenetic medicines that treat hitherto
intractable disease and reverse drug
resistance (23).
(v) Medicines such as ivacaftor that chaperone
defective receptor molecules to improve their scientific knowledge to the development of the practice
function (24).
(vi) Medicines such as bortezomib, a proteasome
inhibitor that acts on protein processing and and cellular therapies, the main challenge for schools and
cell-death (25).
(vii) Antiviral agents that can cure rather than
only suppress (26).
(viii) Gene therapies that have less severe off-
target effects and prolong life meaningfully
(27,28).
(ix) Licensed antisense oligonucleotides such as
eteplirsen and nusinersen that improve the
production of functional proteins in severe
muscular dystrophies (29,30).
FUTURE THERAPIES
Small molecules will no doubt continue to be important
but will most likely be increasingly targeted. As such they
may require companion diagnostics to optimise their use.
Several such drugs are already on the market.
Individualisation of therapy will require more pre-
prescription testing but great care much be exercised so
that unnecessary tests are not introduced (31,32).
We can perhaps also predict that macromolecular and
cellular therapies will increase in importance in the form
of a widening range of immunotherapies not only for
treatment of disease but also for its prophylaxis.
The discovery of how to reprogram somatic cells to
pluripotency led to hopes that regenerative medicine could
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Alain Li-Wan-Po
at last become reality (33). It was hoped that with the use
of a patient’s own cells (autologous), problems associated
with immune rejection and poor engraftment could be
overcome. However, clinical success has remained elusive
(34) and the use of donor (allogenic) cells for induction
might well be the better way forward. The history of the
development of therapeutic monoclonal antibodies show
us that persistence eventually pays off. Sales of such
antibodies not exceed over 50 billion dollars annually (35).
A recent report of regeneration of vision with surgical
interventions that preserve endogenous stem or progenitor
cells provides cause for optimism (36,37).
ROLE OF THE CLINICAL PHARMACIST
What then is the role of the clinical pharmacist in this
new genomic era? Over four decades ago, the American
Association of Colleges of Pharmacy, recognising the
rapid changes taking place in pharmacy practice
commissioned and published an influential report on the
future of pharmacy. It recognised that despite ‘the real and
multifaceted differentiation in the practice roles of
pharmacists, there is a common body of knowledge skill,
attitudes and behaviour which all pharmacists must
possess’ (38). In redefining pharmacy, they called
attention to three key elements: firstly, ready and
secondly, competencies to serve; and thirdly service to
meet both individual and societal needs.’
I think that, by and large, these elements are still key.
For this presentation, I draw attention to another of their
main perceptions: ‘a lack of an adequate number of
clinical scientists who can relate their specialized
skills required to provide effective, efficient and needed
patient services.’ Although as we have indicated, what is a
drug has expanded to include an array of immunotherapies
leaders of pharmacy is probably still the training of
sufficient numbers of clinical scientists with expert
knowledge of drugs.
It may be fitting to end my presentation with Paul
Ehrlich’s words, uttered over a century ago:
‘..to allude to my quotation from Bacon, we no longer
find ourselves lost on a boundless sea but we have already
caught a distinct glimpse of the land which we hope, nay,
which we expect, will yield rich treasures for biology and
therapeutics’ (39).
Many rich treasures have indeed been fdiscovered.
Many more will follow. However, the licensing of targeted
agents now involves testing fewer subjects prior to
marketing. As custodians of drugs, clinical pharmacists
will no doubt wish to ponder on some more of Ehrlich’s
words:
‘I have before me the records of over 9,000 cases. …
The primary object of these large numbers is to explore the
possible dangers of the remedy, because nothing less than
an accurate knowledge of these will provide a sound basis
for the introduction of a new medicament into general
@Real Academia Nacional de Farmacia. Spain