Pro-Test Blogs!

There are about ¼ million people in the UK with paralysis due to stroke, and another 50 thousand due to spinal cord injuries. There is therefore huge incentive to learn how to bypass the damaged parts of the brain by a brain-machine interface so that the patients can regain effective movements that would be a huge help in their daily lives. It is not surprising that there has been widespread press coverage of a study published online in Nature yesterday (1) that signalled a major breakthrough in this field.

http://news.bbc.co.uk/1/hi/sci/tech/7423184.stm

http://www.independent.co.uk/news/science/a-small-bite-for-a-monkey-a-giant-leap-for-mankind-835851.html

Using 2 rhesus monkeys Andy Schwartz and his team at the University of Pittsburg have made a huge advance towards that aim. They trained the monkeys to use their own motor cortical activity to control a mechanized arm to feed themselves. The team extracted the control signal from recording from about 50 nerve cells in the animals’ motor cortex. This was far fewer neurons than many researchers thought would be necessary, an important discovery in itself that should make it a little easier to design electrode implants in future. Once the monkeys got used to the system they soon became astonishingly fluid, skilled and expert in moving the robot arm just by altering the firing of their motor cortical neurones. They even learnt to take advantage of the marsh mallows sticking to the robot fingers to speed its delivery to their mouths. Even though clinical use for people with disabilities is still years away because the arm requires large computers, bulky equipment and a full time technician, and the brain-implanted electrodes would not last a lifetime and lack touch feedback from the arm, Schwartz's achievement is phenomenal and a huge leap towards helping all those people with paralysis.

It is important to emphasise that this work could not have taken place without many years of animal experiments, with monkeys playing a key role (2,3). Andy has been working with monkeys trained to make movements designed to reveal how the motor cortex works for some 20 years. Only monkeys have the kind of control over their hands that we have, so only using monkeys could he work out the kind of control signals that they use to feed themselves. 20 years of monkey experiments (only using 1 or 2 a year) allowed him to ‘take the system to pieces’ and work out how the motor cortical cells control the arm. Obviously these experiments couldn’t be done on humans, they are simply too risky at this early stage in the development of the technology, but now he’s elucidated the control circuitry it will not be long before they'll be applied to benefiting paralysed humans.

Kind regards,

John Stein
Professor of Physiology, Magdalen College, Oxford

1) Velliste M. et al. "Cortical control of a prosthetic arm for
self-feeding" Nature. 2008 May 28. [Epub ahead of print]

2) Lebedev M.A. and Nicolelis M.A.L. "Brain–machine interfaces:
past, present and future" Trends in Neurosciences Volume 29, Issue
9, Pages 536-546 (2006)

3) Schwartz A.B. et al. "Brain-Controlled Interfaces: Movement Restoration with Neural Prosthetics" Neuron Volume 52, Issue 1, Pages 205-220 (2006)

Huntington's disease is an inherited neurological disease that affects
more than 6,000 people in the UK and for which there is no effective
treatment or cure. An important step to developing new treatments was
announced
earlier this week when scientists at the Yerkes National Primate
Research Center in Atlanta published a paper (1) describing how they
genetically modified rhesus macaque monkeys to carry the defective
huntingtin gene (the
mHtt gene) that causes the disease. This is the first time that monkeys
have been genetically modified to have a human disease and the
achievement of Dr. Anthony Chan and his colleagues has received
widespread news coverage.

http://www.timesonline.co.uk/tol/news/uk/science/article3958803.ece
http://www.telegraph.co.uk/news/1987246/GM-monkeys-given-incurable-brain-disease.html

In the past few years research using a range of transgenic organisms,
including flies, nematode worms and mice, has made important
contributions to our knowledge of how the mHtt gene causes Huntington's
disease (2), and transgenic models have also been vital to the
evaluation of potential treatments (3). These models do not however
fully replicate the cognitive deterioration and behavioral problems that
are associated with Huntington's disease, and can't be used to study all
of the changes that occur in different tissues as the disease slowly
progresses. The genes, physiology and lifespan of monkeys are far closer
to that of humans, so it is hoped that a monkey model of Huntington's
disease will provide new insights into the development of the disease to
complement and confirm the observations made using more distantly
related species. The monkey model will also play an important role in
the preclinical testing of new treatments for Huntington's disease,
since their effect on cognitive abilities can be more readily assessed.

It is important to note that this is just a first step to the
development of a monkey model of Huntington's disease, further
refinement will be necessary before it is ready for use in research.
Other organisms such as flies and mice will continue to account for most
animal research into Huntington's disease. Nevertheless we congratulate
Dr. Chan and his team on their success so far.

1) Yang S.H. et al. "Towards a transgenic model of Huntington's disease
in a non-human primate." Nature. 2008 May 18. [Epub ahead of print].

2) Sipione S. and Cattaneo E. "Modeling Huntington's disease in cells,
flies, and mice." Mol Neurobiol. Volume 23(1), pages 21-51 (2001).

3) Harper S.Q et al. "RNA interference improves motor and
neuropathological abnormalities in a Huntington's disease mouse model."
Proc. Natl. Acad. Sci. USA Volume 102(16), pages 5820-5825 (2005).

Pro-Test welcomed Monday's vote by MPs to allow the creation of hybrid human-animal embryos that will be used to produce stem cells for medical research. This work has the potential to provide new treatments for illnesses such as diabetes, Parkinson's disease and motor neuron disease, and we believe that it should be allowed to proceed in a well regulated manner in the UK.

Several sources of stem cells are now being studied in the UK including adult, induced pluripotent , cord blood and embryonic stem cells, and it is best to explore a variety of methods while there is still great uncertainty as to which will work best for each disease. What is beyond doubt is that animal research plays vital role in the research and refinement that is needed to take stem cell therapies from the laboratory bench to the hospital bedside, and we will continue to support this work.

We wish the stem cell scientists well in their research.

Pro-Test

p.s. Keep an eye on the science blog for recent medical advances made possible through animal research

Newspapers are buzzing with excitement over news that a new vaccine against meningitis B developed by the Swiss pharmaceuticals firm Novartis has performed well in early clinical trials.

http://www.guardian.co.uk/society/2008/may/15/health.medicalresearch
http://www.independent.co.uk/life-style/health-and-wellbeing/health-news/meningitis-defeated-at-last-828286.html

About 1,000 mostly young people catch meningitis B every year in the UK, of whom about 10% die and 25% suffer lifelong injuries, so an effective vaccine is highly desirable. Until now efforts to prevent meningitis B have been hampered by the fact that existing vaccines only protect against a few of the numerous different type B strains of the bacterium Neisseria meningitidis that cause the disease, so the development of a universal vaccine that is potentially effective against a wide range of bacterial strains is a significant advance (1).

The development of the new vaccine is also noteworthy because of how it was done. Vaccine development relies on identifying parts of the bacterium known as antigens that can act as targets for the immune system. Rather than using the usual method of attempting to isolate bacterial protein that might act as antigens the Novartis team led by Dr. Mariagrazia Pizza adopted a "reverse vaccinology" approach where they searched the Neisseria meningitidis genome for genes that encoded proteins that might be useful antigens. They identified over 300 potential antigens, and the next step was to screen these for their ability to stimulate the immune system to produce antibodies that kill bacteria in vitro. This required an intact functioning mammalian immune system, so the researchers used mice (2).

The mice were injected with candidate antigens and later antibodies were harvested from the mice and tested for their bactericidal activity against three distinct strains of Neisseria meningitidis, identifying twenty eight antigens that induced the production of bactericidal antibodies. However none of these 28 antigens were potent enough to be used alone in a universal vaccine, so the researchers next assessed various combinations of the most promising antigens. A vaccine containing 5 antigens was found to induce the production of antibodies that had excellent bactericidal activity against all three strains of Neisseria meningitidis. The multicomponent vaccine was then tested against a panel of 85 type B Neisseria meningitidis strains that represent the global diversity of the bacterium, and was found to be effective against almost all strains, especially the most lethal strains. To check that the bactericidal activity in vitro correlated to an ability to prevent disease rats which had been infected with Neisseria meningitidis were treated with serum containing antibodies from vaccinated mice. Rats that were treated with serum were fully protected, a result that provided good evidence that the multicomponent vaccine works.

This vaccine has now been assessed in human trials involving 150 children, and found to safely stimulate the production of antibodies that kill Neisseria meningitidis. Of course it still remains to be determined if this vaccine does protect against a wide range of meningitis B strains in the field, and larger clinical trials to evaluate this are underway, but the results so far are very promising.

Regards

Paul Browne

1) Novartis press release, May 14 2008. http://www.novartis.com/newsroom/media-releases/en/2008/1218899.shtml
2) Giuliani M.M. et al. "A universal vaccine for serogroup B meningococcus" Proc Natl Acad Sci U S A. Volume 103, Issue 29, pages 10834-10839 (2006).