First published in the NASGP Newsletter on 24 April 2024
In March 2020 President Trump tried do-it-yourself drug repurposing. He touted an antimalarial (and, indeed, bleach) as a preventive and cure for covid-19. If, as he claimed, he was taking hydroxychloroquine, the research evidence is that it did him no good, and he was fortunate because some of those who copied him died as a result. Predictably, supplies ran short for people needing antimalarial prophylaxis or treatment for lupus.
Drug repurposing is big business. Investigating the further potential of existing drugs saves the time – at least a decade – and money – around a billion pounds – required to get a new drug from the drawing board to the prescription pad.
Thirty years ago, in early clinical trials sildenafil wasn’t doing much for angina. But men who took it had penile erections. So started the medical, economic and social history of Viagra, probably the most famous repurposed drug in the history of pharmacology. Since when, it has been further repurposed with less publicity for treating pulmonary hypertension, and is being trialled for high-altitude pulmonary oedema and Raynaud’s.
Few other repurposed drugs enter popular culture, though minoxidil, developed for treating cardiovascular problems, has been sufficiently effective for hair growth to reappear as Regaine on the London Underground.
Even thalidomide has been repurposed since it was withdrawn when its ghastly effects on foetal development were finally acknowledged in 1961. For fifty years the risk it posed loomed so large that no-one seriously considered an alternative use. But it’s now being prescribed again, with appropriate cautions, for leprosy and myeloma.
Vaccines are also fertile sources of repurposing. A century ago Albert Calmette and Camille Guérin spent thirteen years examining 230 subcultures of the bovine TB bacterium. They discovered a strain which gave cattle, and humans, immunity from tuberculosis. BCG works by stimulating ’trained immunity’. This suggested an approach to treating cancer. So it has proved. An infusion of 50ml of BCG in saline solution into the bladder takes a minute. A salsa dance down the road swills the bacteria around, stimulating the immune system to police the urothelium for mutant cells and so reduce the risk of recurrence of bladder cancer to close to zero.
For patients with rare conditions such as epidermolysis bullosa, and for chronic diseases for which no effective medication yet exists, repurposing offers hope. Recently, it has been reported that patients who have received BCG for bladder cancer are less likely to develop Alzheimers, which if clinical trials stand up would offer the hope of a drug superior to those currently available.
As the pandemic demonstrated, repurposing needs to be pursued with scientific rigour. To streamline the process, the UK Medicines Repurposing Programme was set up in 2021 to oversee repurposing development.
The speed of AI exploration will be a game-changer.
No hunches needed.
Hitherto, compounds worth investigating were identified if clinical trials revealed an unexpected effect, or from off-label uses and recreational drug users’ experiences. But these are labour-intensive and hit-or-miss methods. The speed of AI exploration will be a game-changer. No hunches needed. AI colleagues design a suitable algorithm and before the team have drunk their coffee AI has crunched the data and identified promising compounds for research.
Still, the concept of repurposing is no magic wand. The pandemic also led the NHS to undertake a very expensive project converting buildings for use as supplementary hospitals.
Nightingale hospitals were conceived even before lockdown was declared in March 2020. Within a month seven conference centres, concert halls, and venues which had been hosting events as varied as Crufts Dog Show and a gin festival were repurposed as hospitals. Government publicity showed thousands of empty beds waiting for patients to arrive. But they didn’t. By mid-2020, having admitted fewer than a thousand patients, the Nightingale Hospitals were being mothballed. In 2021 some served as vaccination centres. Exeter’s Nightingale is now used as an auxiliary hospital, but by the end of 2021 the other six had been repurposed back to their previous lives.
How was it that these ‘insurance policies’ turned out to be ‘white elephants’? In the rush to respond to the pressures on hospitals was the fact that the NHS was short of 100,000 healthcare professionals overlooked?
Maybe the planners should have considered the advice which the Church of England has drawn up for repurposing more than 8,000 redundant churches. Demand for religious services has decreased, but there remains a need for places for people to meet, work, find entertainment, instruction, and advice. The C of E guidelines consider whether suitable power supplies, parking and staff will be available for the intended purpose, whether it be a swimming pool, a skateboard area or a café – any project that will serve the local community. And, so, as libraries, post offices, banks and drop-in centres close, people in cities as well as remote villages now attend a different kind of service in their local church.
Primary care could exploit this repurposing strategy. Medical prescribing is appropriate for medical problems, but many GPs are frustrated that they can’t adequately address the social problems which afflict so many people. Link workers could refer patients to a café or a stall or a food bank in a local church which would welcome new volunteers. Once patients cross the threshold of a building they may never have entered before, they can discover more opportunities which make a real difference to their lives. And practices could set up their own external groups there: discussion and dispensing of health information might be more effective if conducted away from the clinical atmosphere of a practice.
Once almost immune from criticism, GPs are now in the firing line. Their critics are influential but often have little understanding of the realities of general practice in 2024. As a result, GPs are quitting the NHS and heading to general practice in Australia, or finding non-clinical opportunities for their eminently transferable skills. Some leave medicine altogether to become musicians, civil servants, airline pilots, even builders.
Imaginative repurposing can be worthwhile, but what a loss that doctors should feel the need to repurpose themselves.