Regenerative medicine has immense potential for renewing failing or damaged tissues throughout the body, from the skin on the surface to organs deep inside. But the most exciting prospect is for regeneration of the brain and nervous system, both because the unmet medical need is so great and because the science is so challenging.
There are two complementary approaches to neural regeneration. The more traditional one is cell therapy – putting new neurons – nerve cells – or their progenitor cells into the brain or nervous system.
The first transplants of foetal neurons into Parkinson’s disease patients took place in the 1980s – with mixed results – and today several companies are on the brink of clinical trials of therapies based on stem cells.
They include: ReNeuron of the UK, which is about to test neural stem cells in stroke patients; and Geron, from California, which plans to treat acute spinal injury with nerve cells derived from human embryonic stem cells.
The other possibility is to stimulate the latent power of some human neurons to regenerate themselves. Scientists have long known that neurogenesis takes place in more primitive organisms, including some fish and amphibians, but one of the dogmas of 20th century neuroscience – that adult humans do not make new brain cells – was only overturned in the late 1990s.
The discovery then of adult neurogenesis at the Salk Institute in California has inspired a great wave of research, as scientists and biotechnology companies look for ways to increase the low natural level of brain cell generation, without risking the cancer that might accompany unnatural neural growth.
“Very little is known still about human neurogenesis, because it is difficult to look at the growth of neurons in the living human brain,” says Mike Modo of the Institute of Psychiatry in London. “But in postmortems of stroke victims, there is clear evidence of neurogenesis after the stroke.”
Sygnis Pharma, a German biotechnology company, wants to achieve this effect with a protein called “granulocyte colony stimulating factor” or G-CSF, produced naturally in the brain after a stroke – apparently acting both to reduce cell death in the acute phase and to stimulate subsequent regeneration of blood vessels and neurons.
After successful animal tests, Sygnis is undertaking a clinical trial to assess the efficacy of its G-CSF treatment – which the company calls AX200. About 350 stroke patients are taking part in the double-blinded trial; half will receive an infusion of AX200 and the other half a placebo saline solution.
Results are expected in the middle of next year.
A Swedish company, NeuroNova, is following a similar approach with two neuro-stimulating proteins – both in early clinical trials. One is a formulation of “platelet-derived growth factor” (PDGF) to treat Parkinson’s disease; the other contains “vascular endothelial growth factor” (VEGF) for amyotrophic lateral sclerosis (known in the US as Lou Gehrig’s disease), the most common form of motor neuron disease.
A third neurogenesis company, BrainCells of San Diego, is taking a different tack. It is pursuing the discovery made in 2003 by one of its founders, René Hen of Columbia University, that antidepressant drugs achieve some of their effects by stimulating the growth of neurons in the hippocampus, a brain area involved in learning and memory.
In contrast to Sygnis and NeuroNova, whose early work is focusing on proteins that might help people with serious or acute brain disease, BrainCells is concentrating initially on “small molecule” chemicals that people can take as pills or capsules, with a screening programme that has looked at hundreds of potential drugs to find the ones that best trigger the proliferation of new neurons in cell cultures.
Two of its drugs are already giving promising results in clinical trials with patients suffering from severe depression and anxiety, who do not respond to existing antidepressants.
In terms of results, there may not be much practical difference between the two approaches to brain repair – transplanting neurons and stimulating the brain’s intrinsic growth potential – because animal experiments suggest that cell transplants are particularly good at stimulating neurogenesis. This is because the very presence of newly transplanted cells seems to help the brain repair itself, by activating its own “endogenous” stem cells and growth factors.
Mr Modo says that in cases of serious brain injury or disease, a third component may be necessary for effective treatment. Shrinkage and neuronal death often leave a hole in the brain, which transplanted and regenerated cells cannot fill on their own.
A potential solution then is to add a scaffold, made from biocompatible materials and laden with neurostimulating factors, which can guide and support the cells as they grow.
Neural regeneration may be a young field, with much still to prove, but it is one of the fastest growing and most exciting in the whole of bioscience.
There are two complementary approaches to neural regeneration. The more traditional one is cell therapy – putting new neurons – nerve cells – or their progenitor cells into the brain or nervous system.
The first transplants of foetal neurons into Parkinson’s disease patients took place in the 1980s – with mixed results – and today several companies are on the brink of clinical trials of therapies based on stem cells.
They include: ReNeuron of the UK, which is about to test neural stem cells in stroke patients; and Geron, from California, which plans to treat acute spinal injury with nerve cells derived from human embryonic stem cells.
The other possibility is to stimulate the latent power of some human neurons to regenerate themselves. Scientists have long known that neurogenesis takes place in more primitive organisms, including some fish and amphibians, but one of the dogmas of 20th century neuroscience – that adult humans do not make new brain cells – was only overturned in the late 1990s.
The discovery then of adult neurogenesis at the Salk Institute in California has inspired a great wave of research, as scientists and biotechnology companies look for ways to increase the low natural level of brain cell generation, without risking the cancer that might accompany unnatural neural growth.
“Very little is known still about human neurogenesis, because it is difficult to look at the growth of neurons in the living human brain,” says Mike Modo of the Institute of Psychiatry in London. “But in postmortems of stroke victims, there is clear evidence of neurogenesis after the stroke.”
Sygnis Pharma, a German biotechnology company, wants to achieve this effect with a protein called “granulocyte colony stimulating factor” or G-CSF, produced naturally in the brain after a stroke – apparently acting both to reduce cell death in the acute phase and to stimulate subsequent regeneration of blood vessels and neurons.
After successful animal tests, Sygnis is undertaking a clinical trial to assess the efficacy of its G-CSF treatment – which the company calls AX200. About 350 stroke patients are taking part in the double-blinded trial; half will receive an infusion of AX200 and the other half a placebo saline solution.
Results are expected in the middle of next year.
A Swedish company, NeuroNova, is following a similar approach with two neuro-stimulating proteins – both in early clinical trials. One is a formulation of “platelet-derived growth factor” (PDGF) to treat Parkinson’s disease; the other contains “vascular endothelial growth factor” (VEGF) for amyotrophic lateral sclerosis (known in the US as Lou Gehrig’s disease), the most common form of motor neuron disease.
A third neurogenesis company, BrainCells of San Diego, is taking a different tack. It is pursuing the discovery made in 2003 by one of its founders, René Hen of Columbia University, that antidepressant drugs achieve some of their effects by stimulating the growth of neurons in the hippocampus, a brain area involved in learning and memory.
In contrast to Sygnis and NeuroNova, whose early work is focusing on proteins that might help people with serious or acute brain disease, BrainCells is concentrating initially on “small molecule” chemicals that people can take as pills or capsules, with a screening programme that has looked at hundreds of potential drugs to find the ones that best trigger the proliferation of new neurons in cell cultures.
Two of its drugs are already giving promising results in clinical trials with patients suffering from severe depression and anxiety, who do not respond to existing antidepressants.
In terms of results, there may not be much practical difference between the two approaches to brain repair – transplanting neurons and stimulating the brain’s intrinsic growth potential – because animal experiments suggest that cell transplants are particularly good at stimulating neurogenesis. This is because the very presence of newly transplanted cells seems to help the brain repair itself, by activating its own “endogenous” stem cells and growth factors.
Mr Modo says that in cases of serious brain injury or disease, a third component may be necessary for effective treatment. Shrinkage and neuronal death often leave a hole in the brain, which transplanted and regenerated cells cannot fill on their own.
A potential solution then is to add a scaffold, made from biocompatible materials and laden with neurostimulating factors, which can guide and support the cells as they grow.
Neural regeneration may be a young field, with much still to prove, but it is one of the fastest growing and most exciting in the whole of bioscience.
No comments:
Post a Comment