A team of scientists at Lund University in Sweden developed a new drug for pulmonary fibrosis by accident while working on a potential cancer treatment. The drug binds to and inhibits a protein called galectin, slowing the progression of lung scarring in pulmonary fibrosis patients. This promising drug was licensed by Bristol-Myers Squibb for $444 million, and approved by the FDA to treat idiopathic pulmonary fibrosis. The success of the drug demonstrates how serendipity can play a role in medical discoveries.

1. A Spoonful of Sugar, a Remarkable Success
Maria Luisa Verteramo
Centre for Analysis and Synthesis, Lund University
A sugar derivative is the newest, promising and
successful drug for pulmonary fibrosis that is com-
ing from Lund University laboratories in Sweden. Its
success is undeniable and it is demonstrated by the
attention it raised from one of the global pharmaceu-
tical companies, the Bristol-Myers Squibb.
An expertise team of scientists was working on the synthe-
sis and development of specific sugar molecules when, as
commonly happens in medicine, serendipity played a ma-
jor role as confirmed by the words of Ulf Nilsson, Professor
at Lund University during an interview for LTH:
“The original idea was to develop a cancer drug, but, in-
stead, it was found that the molecules had a positive effect
on fibrotic disease, such as pulmonary fibrosis”.
Pulmonary fibrosis is a chronic disease that affects among
200,000 and 300,000 patients in the just only the West-
ern world. Before 2011 there were no selective medicines
for this disease, but in that year Professor Ulf Nilsson
and Professor Hakon Leffler from Lund University together
with Professor Tariq Sethi from King’s College London and
Hans Schambye from Copenhagen decided to combine
their competences and founded a company, the Galecto
Biotech AB. In November 2014 Bristol-Myers Squibb has
entered into an option agreement to aquire the Galecto
Biotech AB for 444 million of dollars and in the later March
2015 the Food and Drug Administration approved the use
of this drug for the treatment of patients with idiopathic
pulmonary fibrosis.
The term Serendipity was coined for the first time
by Horace Walpole in 1754, but he admitted to
be inspired by a Persian fairy tale whose heroes
were always making discoveries, by accidents and
sagacity, of things they were not in quest of.
The chance is an event, but serendipity is a ca-
pacity of some individuals to "see bridges where
others saw holes" and connect events creatively,
based on the perception of a significant link.
Some Serendipity inventions:
Penicillin (Fleming, 1928)
Teflon (Plunkett, 1938)
Microwave oven (Spencer, 1946)

2. 2 MARIA LUISA VERTERAMO
The Idiopathic Pulmonary Fibrosis is a progressive, ir-
reversible age-related lung disease consisting of irregu-
lar deposit of tissue between the alveoli in the lungs that
cause scarring of the tissue and coughing, shortness of
breath and recurrent lung infections in the patients. It is a
fatal disease; after diagnosis it has been estimated about
3 to 5 years of life. The drug has the role to slow down the
process of lung fibrosis and therefore permits to prolong
and improve the quality of life in patients affected by this
disease.
Comparison between healthy lungs (top) and lungs
affected by idiopathic pulmonary fibrosis (bottom).
Also immunity, inflammation and cancer
The drug effectiveness is related to its binding with a
specific protein belonging to a big family of proteins, called
galectins. The galectins family consists of 12 members,
which are present in the whole body, and each of them
is involved in specific biological, both physiological and
pathological processes. Studies demonstrate that they are
involved in cancer, cardiovascular disease, and the pro-
aging process of fibrosis and that this modulation of the
immune and inflammatory responses might have a key
role helping tumors to escape immune surveillance. The
challenging task of the scientific team is to discover how
each galectin influences these processes and how it would
be possible to interfere on those with good inhibitors.
The lock-and-key model
A potent drug is able to strongly inhibit the protein re-
sponsible for the diseases. The mechanism can be sim-
plified with the lock-and-key model. If the lock represents
the protein galectin, the key is the drug, or inhibitor. The
research is based on the idea to develop the key that can
better interact with the lock and investigate their relation.
A team work
Nowadays interdisciplinary groups at Lund University
are involved in studying and understanding these mecha-
nisms.
"We need a lot of different competencies in the research
team: organic chemists who can synthesize small molec-
ular pharmaceuticals, crystallographers who see how the
molecule binds, theoretical chemists who can simulate
the binding event, and so on. As a last touch on the study,
we have a medical doctor who knows everything about
the protein we are working with, and a cell biologist who
can test the substance in cell models", said Mikael Akke,
Professor of Biophysical Chemistry at Lund University
during an interview for the Wallenberg Foundation.
Members of the research team.
The team work in fact consists of several steps and
techniques: advanced organic chemistry, X-ray crystal-
lography, Nuclear Magnetic Resonance, spectroscopy,
calorimetry, fluorescence polarization assays, quantum
mechanical calculations, etc.
The natural molecule that binds the protein is the galac-
tose, a sugar contained in milk. The galactose constitutes
therefore the skeleton in the drug development of the fu-
ture new drugs. The progressive and promising research
of this ambitious group will lead to the discovery of further
innovative medicines effective for inflammation, immunity
diseases and maybe also cancer.
It’s all about sugars! It was 1964 when Mary Poppins was
singing “a spoonful of sugar helps the medicine go down in
a most delightful way” and in 2015 the research on sugars
at Lund University laboratories is demonstrating that she
was not that wrong.