Advances in Medicine Trivia Quiz

Answer: They interfere with protein function

Small molecule inhibitors are chemically synthesised drugs with low molecular weights, meaning their sizes are very small. Because of their small size they readily pass through the cell membrane to reach intracellular targets. These drugs typically interfere with protein-protein interactions within the cell, thereby affecting cellular processes that could be beneficial for cancer growth.

For example, imatinib targets a protein (BCR-ABL) that is only seen in chronic myeloid leukaemia (CML) cells. BCR-ABL activates pathways that promote cell proliferation. Imatinib binds to and blocks the active site of BCR-ABL, thereby preventing BCR-ABL from carrying out its tumour-promoting function. Imatinib has proven to be efficacious in treating CML, sometimes achieving complete remission.

It is marketed under the tradename Gleevec.

Answer: Monoclonal antibodies

Monoclonal (m) antibodies (ab) are antibodies that are derived from a single clone. This means they all recognise the same target with the same degree of specificity. Monoclonal antibodies are designed to recognise and block the function of specific targets that contribute to the progression of disease. For example, bevacizumab targets vascular endothelial growth factor A (VEGF-A), a protein that stimulates growth of new blood vessels to feed a growing tumour. By inhibiting VEGF-A, a tumour's blood supply is cut off and the tumour cannot grow.

Trastuzumab recognises the HER2 protein expressed by some breast cancers. HER2 promotes cell growth, hence aberrant expression of HER2 can lead to tumour formation. Targeting of HER2 by transtuzumab inhibits the cell proliferative function of HER2 and reduces the growth of the tumour.

Beyond acting directly on their targets, the binding of monoclonal antibodies to tumour cells also attracts immune cells to the tumour site and stimulates these immune cells to kill cancer cells.

Other than cancers, monoclonal antibodies have also been used to treat autoimmune and inflammatory conditions such as rheumatoid arthritis and ulcerative colitis.

Answer: Immune cells

In CAR-T therapy, which has been dubbed the "living drug", T cells of the immune system are isolated from the patient and engineered in a laboratory to recognise specific targets expressed by the patient's cancer cells. These targets may be experimentally determined in the lab by taking a small sample of the cancer and then screening for proteins that are expressed by most, if not all, the cancer cells.

The target protein should not be one that is found on a normal cell. After engineering the T cells to recognise these cancer protein targets, the T cells are then grown in the lab until they number billions and are re-introduced into the patient where they recognise, attack and destroy the cancer cells.

At present, this therapy is limited to blood tumours such as leukaemias and lymphomas because of challenges in getting the re-programmed T cells to travel to, penetrate and survive in solid tumours. During clinical trials in patients for whom all other therapies failed, CAR-T therapy induced complete and lasting remission in a large number of study participants.

Answer: A nucleic acid drug

Nusinersen is the generic name for a drug used to treat spinal muscular atrophy. It is an antisense oligonucleotide (ASO), which is a short sequence of nucleic acids tailored to recognise a specific messenger RNA (mRNA) sequence. Spinal muscular atrophy is caused by a mutation in the survival of motor neuron 1 (SMN1) gene that causes its protein product, SMN, to lose its function. There is another gene, called SMN2, that also produces SMN proteins but the proteins produced by SMN2 are often shorter and not fully functional compared with proteins from SMN1. Nusinersen is designed to recognise SMN2 at the region that normally gets cut by cellular processes to form the shorter protein. In this way, nusinersen blocks the cutting machinery and the full length, functional protein can be produced from SMN2.

Nusinersen is injected intrathecally into the central nervous system. Infants with spinal muscular atrophy who are given nusinersen exhibit improvements in motor neuron function that possibly corresponds to normal development. The drug has to be administered every four months and costs a six-figure sum per injection, raising questions of ethics and fair pricing for the afflicted. The tradename for nusinersen is Spinraza.

Answer: A cocktail of drugs that target viral replication

Highly active antiretroviral therapy is the co-administration of at least three drugs that inhibit viral replication by separate mechanisms. This is to counteract possible resistance to any single drug. The primary aim of HAART is to reduce transmission of HIV, including that of mother to child.

The precise combination of drugs is customised for each patient. It is recommended that HAART be administered within a week of confirmed diagnosis and detectable viral load. While HAART does not eliminate the virus from the body, it is able to suppress viral loads to barely detectable amounts and maintain adequate levels of T immune cells that are normally destroyed by HIV. HAART has greatly improved the quality of life and lifespan of HIV-infected individuals by delaying or preventing progression to AIDS, thereby transforming what was once a death sentence into a chronically managed disease.

Answer: Ebola virus disease

Ervebo is the brand name for the Ebola Zaire vaccine, a vaccine used to prevent Ebola virus disease caused by the Zaire ebolavirus species. There are four ebolavirus species that can cause Ebola virus disease, an often fatal haemorrhagic fever, and the Zaire ebolavirus accounts for the most number of outbreaks and the highest mortality rate. Ervebo is a viral vector vaccine, meaning that a separate, relatively harmless, virus is used to deliver part of the Ebola virus to the body for immune recognition.

The viral vector used is a live, inactivated vesicular stomatitis virus (VSV) whose surface protein has been replaced with that of the Ebola virus. VSV causes something like foot-and-mouth disease in cattle. The engineered VSV delivers the Ebola surface protein to the immune system for recognition and thus immunity against Ebola is gained. Ervebo was granted emergency use during the African Ebola outbreaks of the 2010s and was almost 100% effective in preventing transmission compared with unvaccinated individuals, especially when given immediately after virus exposure.

Answer: SMILE

Small incision lenticular extraction (SMILE) is a laser-based refractive eye surgery similar to laser-assisted in situ keratomileusis (LASIK). In LASIK, a small flap is cut on the surface of the cornea and the underlying corneal layer is reshaped with a laser to correct vision problems caused by refractive errors.

The flap is then carefully replaced and allowed to adhere naturally during the healing process. SMILE differs from LASIK in that no flap is cut. Instead, a thin disc (called a lenticule) is sculpted out from under the corneal surface with a laser and removed through a small incision in the cornea. SMILE has a shorter surgical time than LASIK and, because no flap is cut, there is a decreased risk of post-operative dry eyes.

As an added advantage, the excised lenticule can potentially be stored for future reversal procedures at a time when the patient's myopia decreases and age-related presbyopia develops.

Answer: Bionic eye

The bionic eye consists of an electrode array that is implanted in the retina. It receives wireless signals from a camera mounted on a pair of spectacles and transmits these signals to the brain. The implants enable recipients to discern shapes and perceive black-and-white images.

At present, the bionic eye is limited to people who suffer vision loss due to retinal degeneration but still retain a functional optic nerve. While chromatic vision and visual acuity are not yet possible with current devices, next-generation implants are already being developed that could improve prosthetics for the visually impaired.

Answer: Gives prosthetics a sense of touch

Targeted reinnervation is the transfer of nerves severed by amputation to a spare muscle that has been rendered non-functional by the amputation. The existing nerves of the spare muscle are first denervated (deactivated). Residual nerves that originally supplied the amputated limb are then transferred to the spare muscle and allowed to regenerate there.

A motorised prosthesis can be connected to these transferred residual nerves, allowing the user to control the prosthetic limb neurologically. With training and practice, the user might be able to have limb function similar to a natural limb.

Besides nerves that control motion, this technique may also be applied to nerves that detect sensation, thereby giving prosthetics a sense of touch

Answer: Brain seizures

Anti-epileptic drugs are the treatment of choice in the management of epilepsy. In cases where the patients do not respond to drugs, surgical resection of the affected brain region may be considered. However, when the region of the brain involved cannot be safely isolated neurostimulation may be a viable alternative.

Responsive neurostimulation is a closed-loop system in which a pulse generator and leads are implanted in the brain. The device detects and monitors neural activity and when abnormal activity is detected it delivers electrical impulses through the leads to reduce seizure frequency.

Responsive neurostimulation differs from two earlier open-loop neuromodulatory techniques, vagus nerve stimulation and deep brain stimulation. In the open-loop systems, scheduled, intermittent impulses are delivered without detecting or recording brain activity, meaning electrical impulses are delivered whether or not the brain experiences abnormal activity.