The EconomistMarch 14th 2020 Technology Quarterly |Personalised medicine 92
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eing ableto see all the details of the genome at once necessar-
ily makes medicine personal. It can also make it precise. Exam-
ining illness molecule by molecule allows pharmaceutical re-
searchers to understand the pathways through which cells act
according to the dictates of genes and environment, thus seeing
deep into the mechanisms by which diseases cause harm, and
finding new workings to target. The flip side of this deeper under-
standing is that precision brings complexity. This is seen most
clearly in cancer. Once, cancers were identified by cell and tissue
type. Now they are increasingly distinguished by their specific ge-
notype that reveals which of the panoply of genes that can make a
cell cancerous have gone wrong in this one. As drugs targeted
against those different mutations have multiplied, so have the op-
tions for oncologists to combine them to fit their patients’ needs.
Cancer treatment has been the most obvious beneficiary of the
genomic revolution but other diseases, including many in neurol-
ogy, are set to benefit, too. Some scientists now think there are five
different types of diabetes rather than two. There is an active de-
bate about whether Parkinson’s is one disease that varies a lot, or
four. Understanding this molecular variation is vital when devel-
oping treatments. A drug that works well on one subtype of a dis-
ease might fail in a trial that includes patients with another sub-
type against which it does not work at all.
Thus how a doctor treats a disease depends increasingly on
which version of the disease the patient has. The Personalised
Medicine Coalition, a non-profit advocacy group, examines new
drugs approved in America to see whether they require such in-
sights in order to be used. In 2014, it found that so-called personal-
ised medicines made up 21% of the drugs newly approved for use
by America’s Food and Drug Administration (fda). In 2018 the pro-
portion was twice that.
Two of those cited were particularly interesting: Vitrakvi (laro-
trectinib), developed by Loxo Oncology, a biotech firm, and Onpat-
tro (patisiran), developed by Alnylam Pharmaceuticals. Vitrakvi is
the first to be approved from the start as “tumour agnostic”: it can
be used against any cancer that displays the mutant protein it tar-
gets. Onpattro, which is used to treat peripheral-nerve damage, is
the first of a new class of drugs—“small interfering rnas”, or sir-
nas—to be approved. Like antisense oligonucleotides (asos), sir-
nas are little stretches of nucleic acid that stop proteins from be-
ing made, though they use a different mechanism.
Again like asos, sirnas allow you to target aspects of a disease
that are beyond the reach of customary drugs. Until recently, drugs
were either small molecules made with industrial chemistry or
bigger ones made with biology—normally with genetically engi-
neered cells. If they had any high level of specificity, it was against
the actions of a particular protein, or class of proteins. Like other
new techniques, including gene therapies and anti-sense drugs,
sirnas allow the problem to be tackled further upstream, before
there is any protein to cause a problem.
Take the drugs that target the liver enzyme PCSK9. This has a
role in maintaining levels of “bad” cholesterol in the blood; it is the
protein that was discovered through studies of families in which
congenitally high cholesterol levels led to lots of heart attacks. The
first generation of such drugs were antibodies that stuck to the en-
zyme and stopped it working. However, the Medicines Company, a
biotech firm recently acquired by Novartis, won approval last yearKill or cure?
New drugs are costly and unmet need is growing. Pharma needs
new ways of doing thingserative disease which affects from five to 10 people per 100,000. The pharmaceutical industry
Antisense drugs are particularly exciting to patients with rare
congenital diseases because they can be easily tailored. Once the
sequence of the gene for the protein at fault is established, an aso
can be ready in under a year, says Art Krieg, the boss of Checkmate
Pharmaceuticals, a biotech company. The fact that asos are based
on sequences means that they can be “programmed” to inhibit the
synthesis of a wide range of proteins. An asocan also be designed
and used to treat a disease unique to a single patient—what doc-
tors call an n-of-1 trial.
When she was six, Mila Makovec was diagnosed with Batten
disease, in which a defect in a gene called CLN3causes proteins
and lipids to build up in the brain. That build-up was progressively
robbing her of movement, sight and thought. It was eventually go-
ing to kill her. In 2017, though, sequencing showed that Mila’s ver-
sion of Batten disease was not down to a good protein not being
made, as most cases are, but an unhelpful version of another pro-
tein. Tim Yu, a neurologist at Boston Children’s Hospital who
knew about the asobeing used to stop harmful proteins being
made in sma,realised that a similar approach might work for Mila.
The girl’s parents raised $3m dollars through crowdfunding to
create Mila’s Miracle Foundation. With some of that Dr Yu de-
signed an asotailored directly to Mila’s genome and got it pro-
duced. The molecule, called milasen, seems to have helped. The
foundation is now trying to get the same thing done for hundreds
of other very rare diseases.
A lot of charities are doing similar things. Some are big: the
Chan Zuckerberg Initiative has kick-started work on various other
rare diseases with its Rare As One Network. The n-Lorem Founda-
tion, launched this year, also aims to make the development of
asos easier. Some are small, like the one Rohan Seth, an entrepre-
neur, started for his six-month-old daughter Lydia. An asoto deal
with the mutation in KCNQ2that is making her progressively more
disabled cannot come soon enough. Dr Nizar watches approvingly.
The disease which afflicts her family is not yet amenable to this
particular approach. But there may be more miracles on the way. 7