Quick questions on Disease management: pharmaceuticals, gene therapy, lifestyle: HSC Biology Module 8

Pharmaceuticals modify physiology by targeting receptors, enzymes, transporters or ion channels. They are the workhorse of chronic disease management.

Gene therapy modifies the patient's DNA to correct a genetic defect. Two main approaches:

Lifestyle interventions modify behavioural risk factors and often work on multiple diseases at once.

Example 1. Trikafta (elexacaftor/tezacaftor/ivacaftor) for cystic fibrosis in Australia. Listed on the PBS in April 2022, Trikafta is a triple-combination small-molecule drug that corrects the F508del CFTR mutation underlying around 70 percent of cystic fibrosis cases. The three drugs work together: elexacaftor and tezacaftor act as "correctors" that help misfolded CFTR protein reach the cell membrane, while ivacaftor is a "potentiator" that opens the chloride channel once it arrives. Lung function (FEV1) improves by an average 14 percent within weeks of starting therapy, and pulmonary exacerbations drop by 63 percent.

Cytotoxic agents (cisplatin, doxorubicin, paclitaxel) damage rapidly dividing cells; selective for cancer but with collateral toxicity to bone marrow, gut and hair follicles.

A functional gene is delivered to the patient's cells, usually by a viral vector (adeno-associated virus, lentivirus).

Cas9 nuclease guided by a short RNA precisely cuts a chosen DNA sequence, which the cell repairs through homology-directed repair (introducing a correct sequence) or non-homologous end joining (disabling a gene).

Potentially curative; targets root cause; one-time treatment.

Cost (Casgevy approximately 3 million Australian dollars per patient); access (specialist centres only); off-target editing risk; ethical concerns around germline editing.

150 minutes of moderate aerobic activity plus 2 sessions of resistance training per week reduces cardiovascular mortality by approximately 30 percent, improves insulin sensitivity, and reduces depression and dementia risk.

Australian guidelines recommend no more than 10 standard drinks per week. Reduction reduces hypertension, atrial fibrillation, liver disease and several cancers.

Chronic sleep deprivation and unmanaged stress contribute to hypertension, insulin resistance and depression. Cognitive behavioural therapy is effective for both.

"Outline" wants brief points; "describe" wants the steps in order; "compare" wants the same criteria for both approaches (mechanism, reach, cost, cure); "evaluate" demands a justified judgement that weighs strengths against limitations.