Drugs of the future

The future may bring alternatives to the treatments we know today

Small-chemical drugs will be the principal pharmaceutical tools for the foreseeable future, although monoclonal antibodies and proteins will have an increasing impact.

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 behind gene therapy is that a gene is delivered into cells and begins to make a therapeutic protein; for example, people with cystic fibrosis, who lack a working version of a protein known as CFTR, would receive a copy of the CFTR gene.

The initial enthusiasm for the potential of gene therapy hit a major setback in 1999. With the death of Jesse Gelsinger in a gene therapy clinical trial, support fell and the FDA suspended numerous other clinical trials.

Despite this, massive progress has been made over the past 15 years. Scientists are beginning to understand more clearly how to successfully deliver genes into a living cell. As a result, in 2012, Glybera (which is used to treat pancreatitis) became the first gene therapy treatment to be recommended by the European Medicines Agency and is now available to patients.

RNAi

RNA interference (RNAi), which gained a Nobel Prize in Physiology or Medicine 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.

Clinical trials using RNAi continue for several diseases, such as macular degeneration (a form of blindness). 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, possibly because large doses of RNA were used. Despite their potential, RNAi-based therapeutics continue to be fraught with challenges. The severity of these issues caused the large pharmaceutical company Novartis to walk away from RNAi research in 2014.

Nanotechnology

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’).

Targeting will be crucial for many applications. 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 some interest in using this property for the controlled release of drugs.

Nano-based 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 after tissue damage.

Nanotechnologies also show significant promise in diagnostics (for example, through ‘lab-on-a-chip’ technologies, or the detection of very low concentrations of key metabolites) and medical imaging. 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. If the properties of nanomaterials differ fundamentally from their everyday counterparts, can they be considered the same substance? There are also concerns about the possible environmental impact of nanoparticles. (See ‘Big Picture: Nanoscience’ for more.)

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 seem to secrete compounds that promote wound healing, and they have been shown to be just as good (and cost-effective) as conventional medications for chronic wounds. Greenbottle larvae are also 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 using parasitic worm eggs to treat 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.

Lead image:

OakleyOriginals/Flickr CC BY

About this resource

This resource was first published in ‘Drug Development’ in January 2008 and reviewed and updated in August 2014.

Topics:
Genetics and genomics, Medicine, Biotechnology and engineering
Issue:
Drug Development
Education levels:
16–19, Continuing professional development