Drugs of the future
Other approaches are also being researched:
Gene therapy
In the 1980s, there were high hopes that gene therapy would open up a wealth of new treatments, particularly for inherited conditions. The idea is that a gene is delivered into cells and begins to make a therapeutic protein. So people with cystic fibrosis, who lack a working version of a protein known as CFTR, would receive a copy of the CFTR gene.
Unfortunately, the promise has yet to be realised. It has proved difficult to get active DNA into the nucleus and stably active. Progress has been slower than expected, and also suffered after the death of a patient, Jesse Gelsinger, in a clinical trial in 1999. A further setback came in 2003, when French patients developed cancer linked to the integration of a viral vector into their DNA.
Nevertheless, clinical trials are underway in a number of conditions, including muscular dystrophy and Parkinson's disease. Gene therapy is also being tested in some cancers, though the aim is to kill cells rather than repair them. Routine use, however, remains a long way off.
RNAi
RNA interference (RNAi), which gained a Nobel Prize for its discoverers in 2006, is a new and highly promising strategy. RNAi is used to eliminate (or 'knock down') specific proteins from a cell, such as those causing a disease. It is based on an unusual phenomenon: short RNA molecules triggering highly specific destruction of messenger RNA molecules containing the same RNA sequence. Its normal role is probably to protect against viruses invading the cell.
The medical possibilities are very broad. Examples include knocking down the receptor for a virus, or an overactive protein causing cancer or messenger molecules promoting inflammation.
A small number of clinical trials have begun, for example for macular degeneration (a form of blindness). But it is early days. As in gene therapy, it is difficult to deliver the RNA and there are worries that other, useful proteins might be eliminated. One study in mice led to severe liver damage in animals, possibly because large doses of RNA were used.
Nanotechnology
As discussed in ‘Big Picture on Nanoscience’, nanotechnology-based solutions are being tested in a variety of conditions.
Some applications depend on the unusual properties of materials at the nanoscale. Nanoscale silver is toxic to bacteria and is being used in wound dressings (silver-impregnated pyjamas have been suggested for hospitals). Gold nanoparticles can convert some wavelengths of light into intense heat, and are being tested as a possible cancer treatment (a 'thermal scalpel').
Critical to many applications will be targeting. Antibodies could target a toxin-linked nanoparticle to a cancer cell.
More generally, because they are so small, weight-for-weight nanoparticles have a very high surface area. There is interest in using this property for controlled release of drugs.
Nanobased structures are being explored as molecular scaffolds for tissue repair. Some exciting applications combine a physical support role for nanomaterials with bioactive molecules attached to a nanoscale scaffold. This approach could be used to encourage bone or nerve growth following tissue damage (see Rebuilding site, ‘Wellcome Science’ issue 2 [PDF 1MB]).
Nanotechnologies also show significant promise in diagnostics (for example, through 'lab-on-a-chip' technologies, or by detection of very low concentrations of key metabolites) and medical imaging (see Chips with everything). Another exciting possibility is to link detection to treatment - so a diagnostic device automatically delivers the required medication. In animal studies, nanoparticles have been used both to detect blood glucose levels and to release insulin.
Nanotechnologies are undoubtedly an area of great promise. Given the diversity of approaches they encompass, they could have a profound impact on healthcare. Initially they may enhance current treatments, but entirely new agents could soon become available.
However, nanotechnologies also raise challenging regulatory issues - the properties of nanomaterials differ fundamentally from their everyday counterparts; can they be considered the same substance? And there are concerns about the possible environmental impact of nanoparticles.
A living thing
As well as chemically produced agents, researchers are also looking at living organisms. In doing so, they are reviving a long and colourful medical history.
Leeches may not be everyone's cup of tea, but they produce a very useful anti-blood-clotting agent (hirudin) and are very effective at draining blood. They are used clinically in microsurgery, helping to improve blood flow when digits are reattached.
Maggots may be similarly repellent to most, but they have long been medicinally useful. In World War I, infections with maggots kept bacterial infections in check. Experiments have been carried out with maggots to clean wounds; they also seem to secrete compounds that promote wound healing. They have been shown to be just as good (and cost-effective) as conventional medications for chronic wounds, and greenbottle larvae are commercially available for use in medicine. The main obstacle to their wider use is patient squeamishness…
An area of growing interest is the use of parasites or their secretions or eggs to manipulate the immune response. There is a school of thought that the current high incidence of asthma, inflammation and allergy in the West is due to a lower parasite burden. In parts of the world where parasites are common, asthma is rare. Various trials have been carried out of parasitic worm eggs for inflammatory bowel disease, with some success. In the UK, hookworms are being tested as a treatment for asthma.
Much effort is being put into identifying the active substances produced by parasites, so that they can be given medicinally without a patient having to be infected with the real thing.