Thalidomide

Recent Research and

Effect on Development

Submitted by: Siamlalven

EID: A281155422006
Foundation of Development Psychology – I
B. A. Psychology (H+R), 3rd semester
Amity University Punjab, Mohali
Submitted to: Dr. Samita
Introduction

Thalidomide is a sedative drug first developed by a Swiss pharmaceutical company,

CIBA, in the early 1950s, and subsequently synthesized in 1954 in Western Germany by the
firm Chemie Grünenthal GmbH, who found out that thalidomide had interesting sedative
effects. The drug was initially marketed as a sedative and appeared as a promising alternative
to Barbiturates, which would allow users to undergo a deep sleep in the absence of a
hangover and with a reduced risk of developing drug dependency.
In April 1958, thalidomide was advertised by The Distillers Company (Biochemicals)
Ltd., in the United Kingdom which claimed that the drug could be given with complete safety
to pregnant women and nursing mothers without adverse effect on mother or child. Its
popularity rose among pregnant women as a treatment for nausea and morning sickness due
to its anti-emetic effects. Its increase in usage among pregnant women was assisted by the
fact that a prescription was not necessarily required to obtain it and was affordable.
Unlike the rigorous testing conducted in today’s times when introducing a new drug
in the market, the drug was not evaluated for any potentially dangerous teratogenic effects.
During the pilot stages of testing, researchers at Chemie Grünenthal found that it was
virtually not possible to give test animals a lethal dose of the drug (in accordance with the
LD50 test). The drug was thus deemed to have no toxic effects on humans. Apart from
relieving the symptom of nausea often experienced in early pregnancy, the drug was
prescribed for a range of other conditions including pneumonia, colds, and flu. It was later in
1961 that doctors found that thalidomide caused irreversible damages to the foetus and
thousand of children were born with severe congenital malformations, while some died
shortly after being born or in a few weeks.
Due to the thoroughness of Food and Drug Administration reviewer Frances Kelsey,
the US was spared the fatal catastrophe. The Richardson-Merrell firm applied for
thalidomide's sedative use in 1960. Dr. Kelsey asked for more information regarding the
observed peripheral neuropathy in some patients from Europe. They did not comply, and the
medication was not licensed in the US.

Review of Literature

A study of the available literature on thalidomide reveals that it is a potent medication

with a variety of significant side effects. Researchers and scientists have demonstrated it to
possess anti-inflammatory, immunomodulatory, and anti-angiogenic qualities. Additionally, a
known teratogen, thalidomide might result in birth abnormalities. Because of this, it is
categorized as a pregnancy category X medicine, meaning that it is contraindicated during
pregnancy and should not be used by women who may get pregnant unless the advantages
outweigh the risks.
A variety of anomalies observed in all patient cases included, but were not limited to:
  Phocomelia - a congenital abnormality in which a child's hands and feet are non-
existent or severely undeveloped and are tied to the child's trunk.
 imperfections with the ear.
 anomalies of the eyes.
 facial spasticity.
 injury to internal organs.
 a congenital heart condition.
In 1964, Dr. Jacob Sheskin of Jerusalem's Hadassah University Hospital gave
thalidomide to one of his patients to treat a serious complication of leprosy. As a result, in
1967, the World Health Organization (WHO) conducted a clinical investigation on the use of
thalidomide for leprosy. Thalidomide was then prescribed to treat erythema nodosum
leprosum (ENL), a specific consequence of leprosy. About half of those with lepromatous
leprosy are thought to have ENL, an immunological consequence. It is characterized by a
number of illnesses, such as inflammation of the eyes, lymphadenitis, neuritis, and orchitis.
Given that ENL is an inflammatory illness, thalidomide is a good therapeutic option because
it has anti-inflammatory qualities. One of its modes of action is the suppression of the pro-
inflammatory cytokine TNF- α, which is generated by monocytes, with specificity.
In 1997, thalidomide was used for the first time to treat multiple myeloma. In 2006, it
received formal approval for usage in conjunction with the steroid dexamethasone to treat
myeloma. Thalidomide was the first new medication to effectively treat MM in several
decades, ushering in a new age of "novel therapies." It led to the research and development of
the immunomodulators lenalidomide and pomalidomide, which resulted in enhanced efficacy
and fewer side effects.
Thalidomide stops malignant tumours from growing, metastasizing, and becoming
hyper vascular as a result of its anti-angiogenic qualities. Thalidomide promotes
immunological responses, improves the capability of immune cells known as T cells and NK
(natural killer) cells to kill myeloma cells, and reduces inflammation, just like the other
immunomodulatory medications. Furthermore, it prevents the development of blood vessels,
which are necessary for the survival and expansion of cancer cells.
Thalidomide, which has historically been avoided by HIV-positive people, is useful
for treating aphthous ulcers, gastrointestinal lesions, Kaposi sarcoma, and other HIV-related
conditions. The aetiology of HIV frequently involves immunological activation and
inflammation. When these two circumstances come into play, CD4 T-cell depletion quickens.
This well-known fact shows that in order to fully address HIV infection consequences,
effective anti-inflammatory therapy is necessary.
Thalidomide might be the only solution to the problem. The editorial references a
study that claims that thalidomide may block tumour necrosis factor-alpha and that this
mechanistic characteristic may reduce HIV replication rates. This study was published in the
same issue. In turn, this might lessen inflammation. Global efforts to treat HIV are centred on
understanding HIV proviral latency. Targeted tactics such as latency reversal drugs help the
immune system clear more latently infected cells. Researchers refer to this as a "shock and
kill" medical approach.
 Thalidomide has been considered contraindicated in HIV infection. The use of
thalidomide in people with HIV may be safe and beneficial, according to this current
information. The open label approach and small sample sizes of the current findings,
however, are limitations. Thalidomide's use in HIV would be constrained by prudence and
measures to prevent birth abnormalities, much like with other indications for the drug.

Conclusion

The thalidomide tragedy left a lasting impact on the newborn children of the
1960’s as well as the family members. The pharmaceutical industry has since made
significant efforts to raise the scrutiny of testing before releasing any new medications onto
the market in response to the thalidomide catastrophe. To specifically address potential
developmental toxicity, a set of guidelines were created for all medication testing.

Bibliography
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