Intro and even absent. Only around 40% of these

Intro

Thalidomide, otherwise known as its
brand name Immunoprin, is an immunomodulatory drug (drugs which adjust the
immune response of the body). Today, Thalidomide is mainly used to treat
certain cancers such as myeloma and leprosy.

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First introduced to the market in 1957
in Germany under the name Contregan, it was prescribed as a hypnotic/sedative,
Thalidomide was claimed to treat insomnia, anxiety, tension, and gastritis (inflammation
of the stomach lining). It was given to pregnant women in attempts to alleviate
nausea and morning sickness. On October 1st, 1957, Thalidomide
became an OTC (over-the-counter) medicine in Germany. Afterwards, around
5,000-7,000 babies were born with phocomelia. Phocomelia syndrome (PS) is a rare birth defect that causes
severe birth defects, especially of the upper limbs. The bones of the arms, and
in some cases other appendages, may be extremely shortened and even absent.
Only around 40% of these children survived. Throughout Europe and the rest of
the world, around 10,000 reports of children with phocomelia as a result of
thalidomide. Only 50% of these infants survived. Those exposed to thalidomide
while in the womb sustained limb deficiencies, mainly that their long limbs
either didn’t develop or were stumped. Other effects included deformed
alimentary canal, urinary tracts, eyes, hearts, blindness and deafness. These
harrowing effects led development of more drug regulations and control over
drug use and its structural development. 

Structure/chemistry

Thalidomide has a chemical formula of C13H10N2O4 and its IUPAC name is
2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione

As Thalidomide became available over
the counter, many women were relieved that their morning sickness was gone,
However, a year later thousands of doctors and mothers were horrified as all
these infants had severe deformities. It took Doctors quite some time to
establish the connection until two doctors, Widukind Lenz and William McBride
discovered that Thalidomide was taken by all pregnant mothers during pregnancy.
By 1961, Both doctors confirmed the link between the birth defects and
thalidomide and it was pulled from the shelves, but at this stage thousands of
babies were affected or killed by the drug. Drug testing and regulations
weren’t as rigged or concise back then but eventually, scientists discovered
that the reasoning behind all these birth defects associated with thalidomide
lied with in its chemistry and geometry. Researchers unearthed that there were
two versions of the thalidomide molecule. This is known as isomers.

Isomers are compounds with the same molecular
formula but different structural formulas. Thalidomide is a molecule with three
connected rings of carbon and nitrogen, plus some oxygen and hydrogen, is
what’s known as a chiral molecule. Chemists often think of chiral molecules as
lift or right handed. This is because of the different versions of chiral
molecules, known as enantiomers, contain the exact same elements, but are
arranged differently, almost like a mirror image of one another.

A chiral molecule has an atom
typically carbon with 4 different groups connected to it, that’s called the
chiral centre. A group can be single atom, chains or rings, In some cases two
groups can even be connected. In each enantiomer the group is attached in the
opposite order, so they’re mirror images of each other. Because enzymes and
receptors in in the body’s react with molecules in very specific way and as a
result of enantiomers being mirror images of each other, this means that they
might react very differently.

In the case of thalidomide, scientists
discovered that the R enantiomer alleviated morning sickness but the S
enantiomer caused Phocomelia and
other severe birth defects. After this discovery, researchers believed that
they could isolate the R enantiomer and continue to use it to treat morning
sickness. However, during experimentation, it was discovered that the R
enantiomer can actual change to the R enantiomer in the human body! This in
turn means that even if chemists isolated 100% of the S enantiomer of
thalidomide, it still would be unsafe for use in pregnant women.

Areas
of thalidomide research

Today,
researchers continue to investigate the uses of thalidomide for an array of
illnesses and conditions. Though more information and trials are needed,
thalidomide is shown to be promising in treating

Inflammatory
diseases that affect the skin, such as Bechet’s disease cutaneous lupus
HIV-related throat
and mouth ulcers, body wasting and weight loss.
Cancer,
including bone marrow and blood cancers, E.G. myelofibrosis and leukaemia
and also cancers found elsewhere in the human body.

Side effects
of thalidomide other than birth defects

Patients taking the drug thalidomide may experience
side effects such as:

·        
Blood
clots

·        
Peripheral
neuropathy

·        
Rash

·        
Drowsiness

·        
Dizziness

 

Leprosy
treatment

Jacob Sheskin, Israeli physician, administered the
drug thalidomide to a patient chronically ill with leprosy in 1964. The patient
had Erythema Nodosum Leprsosum (ENL), a very painful skin condition which is
caused by leprosy. Dr. Sheskin attempted this treatment despite the ban of the
use of thalidomide. However, the results ground-breaking as the patient slept
throughout the night and managed to get out of bed without help after waking
up. Afterwards, A clinical trial was carried studying the effects and use of thalidomide
in treating leprosy.

Soon after the teratogenic properties of thalidomide
were established during the 1960’s, the anti-cancer potential was recognised
and clinical trials were carried out in people with advanced cancer, for
example multiple myeloma. The results were ambiguous.

Little research was conducted with thalidomide in
relation to cancer until the 1990s.

 Research into
the role if angiogenesis (the rapid growth of new blood vessels) in the
development of cancer, was conducted by Judah Folkman. In the 1970’s, it was
shown that sold tumours could not grow or expand without it. In 1993 he shocked
the medical world by hypothesizing that this was also true in relation to blood
cancers, and published his work the following year showing that angiogenesis was
a biomarker higher in people with cancer, especially in people suffering from
blood cancers. Simultaneously, Robert D’Amato, a member of Folkman’s team, was
researching the development of angiogenesis inhibitors and unearthed in 1994
that thalidomide inhibited the action of angiogenesis. Around this time,
Folkman was contacted by a man whose wife was dying of multiple myeloma and
treatment was proving ineffective. Folkman convinced the doctor of the woman to
try thalidomide. The doctor then conducted a trial for the effectiveness of thalidomide
of multiple myeloma. As a result, around 33% of patients responded to thalidomide
positively. These results from the trial were then published in the New England
Journal of Medicine in 1999.

Thalidomide has been a catalyst for change in terms
of drug regulations, medicines and history itself during the 1900 hundreds.
Thalidomide has become an effective treatment for debilitating illnesses such
as leprosy and cancer. A drug with endless uses and effects, both lifesaving
and fatal. Thalidomide has showed the devastating  effects of negligence of medicines and safe
practices, which as a result, has taken thousands of innocent lives and left
many people severely deformed. However, if not for this tragedy, medicines may
not be as regulated and safe for you, me or future generations.