The impact of the genomic revolution on medicine was discussed in a keynote address at this year's British Pharmaceutical Conference on September 13. The session was chaired by Professor Martyn Davies (conference science chairman)
The science behind the genome was a fascinating story, said Professor Ray Baker (chief executive, Biotechnology and Biological Sciences Research Council). The genomic revolution was moving quickly, with pharmacogenomics providing opportunities to develop discrete medicines for individuals.
When diseased populations were examined, it was possible to identify disease related susceptibility genes which might make perfect targets for therapy, he said. If the genes themselves were not direct targets then the gene variant might show specific metabolic differences which could be targeted.
By using the human genome, candidate genes could be determined and sequences could be obtained. It would then be possible to obtain the gene sequence and confirm whether the gene was a target worth pursuing.
The single differences in DNA sequences that were present between individuals were known as SNPs [pronounced snips]. These differences, although not necessarily disease forming themselves, could be used to build up SNP maps useful for identifying patterns in diseased populations. Data could be gathered to the advantage of individual patients and the efficacy of particular drugs in clinical trials could be predicted. Adverse drug reactions could also be correlated with SNP/DNA profiles.
This technology might have the effect of refining which populations a drug could be used in and might slim down the drugs market. However, it would make drugs more efficacious overall. For example, it was possible to identify patients who metabolised certain drugs slowly, which led to an accumulation of the drug. This identification had brought advantages to individual patients.
Osteoporosis was a major problem for both women and men. Osteoprotegerin (OPG) had been identified as being involved in the disease process. Genetically engineering mice to over-express the OPG gene resulted in them developing dense bones. If the gene was deleted, the mice developed the disease. This process of genetic manipulation had led to new therapies being developed.
Malaria, too, was an enormous problem, but by mining the genome of the disease causing organism it might be possible to identify susceptible proteins which could be used to develop DNA vaccines. The organism responsible for tuberculosis was smart, complex and had a slow growth cycle. It was also resistant to many of the antibiotic treatments available. By using the genome it might be possible to determine enzymes in the cell wall of the organism which could be used for new diagnostic and therapeutic tools. With the increasing problem of antimicrobial resistance there was a great need for new therapies. If the genome sequence of an organism was known, the processes involved in its pathogenicity could be better understood.
There was no shortage of problems but also no shortage of hope and knowledge of the human genome would lead us directly to new treatments, Professor Baker concluded.