All sizzle and no sausage?

Gene Therapy - the promise and the reality

2003 - Human Genome Project (HGP) completed ahead of schedule and under budget.

So, goodbye to a host of inherited conditions; cystic fibrosis, haemophilia, muscular dystrophy, sickle cell anaemia and goodbye to cancer, too; even though we only inherit a susceptible genotype and not the condition itself, the mutations that lead to cancer are still suitable candidates for gene replacement therapy.

How were these cures going to happen? Easy.

1 – Determine the mutated gene
2 – look up the sequence of that gene in its healthy form
3 – pop the healthy form into a virus
4 – infect the patient with the virus (inactive of course)
5 – the healthy DNA replicates and produces normal protein
6 – Bingo! – one cured patient.

2011 – So, that was the sizzle, but where’s the sausage? Are there any cured patients? Well, yes, but very few [ie Bubble Boy Disease or Severe combined immunodeficiency (SCID) ].

Cancer? No. Well, hardly any. Cystic fibrosis? No. Any others? Nope.

We all knew the HGP was the first step and not the cure, but 7 years of effort and still so little to show? How come?

Well, it’s been a rocky road. Problematic vectors (carriers of the genetic material such as viruses, bacteria, plasmids etc); multifunctional disorders; healthy protein production either transient or at sub-therapeutic levels; inaccessibility of the diseased tissue; non-selective uptake; induced immune response to repeat injections and even tragic consequences such as inducing leukaemia and the death of triallists. Not surprisingly, some are saying that Gene Therapy is too complex and will never deliver.

I disagree. There are far too many clever people and too much money involved for it to fail, but don’t expect the Daily Mail, to announce that “Disease is Dead!” any time soon. We’re talking baby steps, not giant leaps.

Just like in the early days of small molecules, the first gene therapies will be far from perfect. Incomplete therapeutic response and tricky side effects will be the order of the day, but little by little a new generation of therapies will emerge to deliver on the original promise.

When?

At my age, if I’m unlucky enough to contract it, Alzheimer’s is going to have me mislaying my senior railcard long before the cure comes along, but luckily for my children, the Big ‘C’, is likely to become Little ‘c’ as many forms of the disease lose their ‘killer’ status.

And despite being too befuddled to understand, even I might see certain cancers being cured before 2020. Pre-metastatic melanoma for one as it is so accessible and the relative ease of inserting healthy genes into blood and bone marrow, will give us a good shot at the leukaemia family. Solid tumours though; that’s going to prove a bit harder.

So, despite the noisy sizzle that has so far turned out to be the rush of hot air, I’m confident that our sausages are on their way. The first ones might be a bit wonky, but we’ve got some of the world’s best chefs slaving in our kitchens and someday soon, they’ll come up with the gourmet goods; more effective, more curative and with fewer side-effects than even the best of the current, small-molecule chipolatas.

In the next issue, we’ll be looking at the first licensed gene therapy, currently only available in China.

For more information about market research for emerging therapies, contact Errol

The day is free of charge to all and the broad mix of attendees includes young researchers, product managers and marketeers and, this time round, even a nursing clinical lead.

As well as offering a great opportunity to learn new skills and the chance to practice them, the day is also perfect for networking with those who will be the next movers and shakers in our industry.

For upcoming dates and details, contact Andrew Grant