Glimmer of hope

March 24, 2000

Using viruses to transport new genes into the brain may one day offer relief to sufferers of neurological disorders. Geoff Watts reports

Intent on finding a better way to treat Parkinson's disease, the most familiar of all neurological disorders, David Latchman, of London's Institute of Child Health, has turned to gene therapy. Several attempts at devising a cure, including the implantation of cells taken from foetuses, have had limited success. But far from being disheartened by these lacklustre results, he sees them as positively encouraging.

The foetal implants have shown that the course of the illness can be changed, albeit transiently. Armed with that reassurance, Professor Latchman and his colleagues at University College London hope gene therapy will achieve lasting change. "We are about to go into trials in primates," he says, "so we may be able to contemplate initial clinical trials in the next year or two."

The symptoms of Parkinson's disease stem from the death of a group of nerve cells deep within the brain. These cells produce one of its chemical messengers, dopamine. The causes of the failure are disputed. There seems to be some genetic influence; but the environmental factors that must also play a part remain mysterious. Replacing the lost dopamine with drugs will often control the disease for several years. In the end, though, most patients deteriorate.

Professor Latchman aims to introduce at least two genes into the brain. One will carry the instructions for making tyrosine hydroxylase, an enzyme involved in the synthesis of dopamine. The other encodes the recipe for making GDNF, a growth factor that fortifies the dopamine-producing neurones. In animal models of Parkinson's disease, injecting GDNF directly into the brain gives a good response. It seems to work by attaching itself to the outside of cells. So, in theory, it does not need to get inside them to be effective. But injections of GDNF have not worked well in human trials. "You can't deliver enough of the growth factor to the right place without producing side effects," explains Professor Latchman. Gene therapy would bypass the problem.

But why the need to use two genes rather than one? "The most effective therapies are going to be those that treat the disease at its various stages," says Professor Latchman. "So the aim is to enhance the survival of the neurones that are left, while also compensating for the neurones that have been lost."

As with most gene therapy, the big hurdle is getting the new genes into the cells that need them. Like many other researchers, Professor Latchman and colleagues are using a viral vector to perform this feat. Unlike many others they have opted for, the herpes simplex virus, HSV, which causes cold sores.

"HSV is not popular for these purposes because it takes years of working with it to get to know how to use it. The problem isn't getting the new genes into it. The problem is that to prevent its producing cold sores or causing encephalitis, you have to disable it - and that makes it more difficult to grow in culture." Aside from the fact that Professor Latchman is familiar with HSV's eccentricities, its other great advantage for his purposes is that neurones are its regular habitat. "It naturally produces latent infections of the nervous system. The reason people who get cold sores have continual recurrences is that the virus is there all the time, hidden in the nerve cells."

Besides going precisely where it is needed, HSV also possesses an above-average number of genes, giving plenty of options about which ones to remove before slotting in the replacements. The virus Professor Latchman is working on has had four of its genes removed - including, of course, those that allow it to provoke cold sores. One drawback is that the virus, with its new payload, has to be injected directly into the brain. "This is why we're keen that the gene should continue to be expressed in the long term. When the virus becomes latent, it shuts off the expression of all its genes, including any you've put into it. We obviously don't want to have to inject patients every week."

Professor Latchman admits that HSV is difficult to work with. So when the point is reached at which human trials seem justified, the group will probably start with patients suffering from something other than Parkinson's. "We wouldn't be allowed to do anything except with end-stage patients, and that would make it difficult to prove efficacy."

Professor Latchman thinks he may be more successful than others who have used viruses as delivery vehicles but failed to get much action from the new genes. "People have sometimes used off-the-shelf viruses that have been disabled not to deliver genes to explore how the virus works." Professor Latchman's viruses are "custom disabled", or designed specifically for gene therapy. He hopes they will do the delivery job more effectively.

Parkinson's is not the only neurological disorder that might respond well to gene therapy. So too might Alzheimer's and motor neurone disease. There is even the possibility that gene coding for certain protective proteins could be used to minimise some of the damage caused by stroke. Malfunctions of the nervous system contribute a great deal to the worst miseries of old age. Genes clearly have the potential to deal with them - if that potential can be realised.

Please login or register to read this article.

Register to continue

Get a month's unlimited access to THE content online. Just register and complete your career summary.

Registration is free and only takes a moment. Once registered you can read a total of 3 articles each month, plus:

  • Sign up for the editor's highlights
  • Receive World University Rankings news first
  • Get job alerts, shortlist jobs and save job searches
  • Participate in reader discussions and post comments
Register

Reader's comments (1)

I really want to appreciate Dr Oba for using his herbal medicine to cure my herpes o since 3 years now I have been living with this virus and it has been giving me challenges, I was so perplexed cause i have been taking several drugs to be cured but all of my Search like that for google.us was in vain,one morning i was browsing through the Internet then i saw several testimonies about Dr. Oba curing people from Herpes virus and immediately i contacted Dr. Oba on his email: drobaherbalhome2@gmail.com i told him about my troubles and he told me that i must be cured, gave me some instructions and which i rightly followed. so he prepared a herbal medicine for me and sent it to me which i used for 3 weeks and everything was like a dream to me and my Herpes virus was totally gone, why don't you contact him today and be free from your diseases because he is very good and honest Doctor. contact him via email; drobaherbalhome2@gmail.com or call/whatsApp him on +2348111837606

Have your say

Log in or register to post comments

Most commented

Recent controversy over the future directions of both Stanford and Melbourne university presses have raised questions about the role of in-house publishing arms in a world of commercialisation, impact agendas, alternative facts – and ever-diminishing monograph sales. Anna McKie reports

3 October

Sponsored

Featured jobs

Lecturer in Marketing

Edinburgh Napier University

Resource Planner

Bpp University

Faculty, English

Khalifa University

Junior Research Fellow for the Research Project

Vellore Institute Of Technology

Knowledge Exchange Manager, Innovate

Royal Holloway, University Of London