Breakthroughs in Stroke, Brain Cancer, and Tissue Engineering

We may dream of discovering a "fountain of youth," a magic bullet treatment to achieve immortality with just a single elixir, fruit, capsule, or injection. But the modern reality of the anti-aging effort is that, for now, we must attack each killer disease individually.

An impressive new treatment for cerebrovascular accidents -- brain strokes -- was developed at the University of Manchester.

Researchers induced a stroke in the rats and the drug IL-1Ra, or a placebo for comparison, was injected under the skin. The researchers did not know which animals had been given which drug. This is a similar process to what happens in clinical trials of medicines.

The results were startling. MRI scans revealed that the rats that were given IL-1Ra up to three hours after the stroke had only about half the brain damage of the placebo group.

Professor Rothwell said: “This is the first time that we are aware of a potential new treatment for stroke being tested in animals with the same sort of diseases and risk factors that most patients have. The results are very promising and we hope to undertake further clinical studies in stroke patients soon.”

IL-1Ra works by blocking the naturally occurring protein interleukin 1. Researchers at The University of Manchester have identified that it is a key cause of brain injury following a stroke.

Interleukin 1 encourages inflammation in the area of the brain affected by stroke. This sends out signals to attract white blood cells and to switch on microglia cells in the brain. Because the barrier surrounding the brain has been weakened by the stroke the white blood cells find it easier to enter the brain. But instead of helping the inflamed area they actually kill nerve cells and worsen the injury. The increasing presence of these cells also explains why the damage in the brain gets worse over time following a stroke.

IL-1Ra also reduces the amount of damage to the blood-brain barrier following a stroke so the harmful cells can’t enter the brain. In the recent experiments IL-1Ra reduced the damage to the blood-brain barrier by 55% in healthy rats and 45% in rats with underlying health conditions. In all types of rats the drug reduced the amount of activated microglia cells by 40% compared to the placebo group. _Manchester

A similar type of anti-inflammatory therapy is also being developed to combat Alzheimer's, multiple sclerosis, traumatic brain injury, and other forms of neurodegenerative and inflammatory brain disease.

The fight against brain cancer and other solid tumours was advanced recently by the University of Tennessee Space Institute. The technique utilises a femtosecond laser to both precisely target and destroy tumours.

“Using ultra-short light pulses gives us the ability to focus in a well confined region and the ability for intense radiation,” said Parigger. “This allows us to come in and leave a specific area quickly so we can diagnose and attack tumorous cells fast.”

Once the cancerous area is precisely targeted, only the intensity of the laser radiation needs to be turned up in order to irradiate, or burn off, the tumor. This method has the potential to be more exact than current methods and to be done as an outpatient procedure replacing intensive surgery.

“Because the femtosecond laser radiation can be precisely focused both spatially and temporally, one can avoid heating up too many other things that you do not want heated,” said Parigger. “Using longer laser-light pulses is similar to leaving a light bulb on, which gets warm and can damage healthy tissue.”

The technology can be especially helpful to brain cancer victims. The imaging mechanism can non-invasively permeate thin layers of bone, such as the skull, and can help define a targeted treatment strategy for persistent cancer. The method also overcomes limitations posed by current treatments in which radiation may damage portions of healthy brain tissue. It also may overcome limitations of photodynamic therapy that has restricted acceptance and surgery that may not be an option if not all carcinogenic tissue can be removed. _UTSI

Combining the targeting function with the therapeutic heating function saves time and improves therapeutic precision, and the improved precision of targeting saves surrounding normal tissue.

Research engineers at the University of Toronto have developed a new, rapid method of tissue engineering, capable of creating 3-D layered tissues in an advanced hydrogel.

Scientists manipulate biomaterials into the micro-device through several channels. The biomaterials are then mixed, causing a chemical reaction that forms a "mosaic hydrogel"—a sheet-like substance compatible with the growth of cells into living tissues, into which different types of cells can be seeded in very precise and controlled placements.

Unique to this new approach to tissue engineering, however, and unlike more typical methods for tissue engineering (for instance, scaffolding, the seeding of cells onto an artificial structure capable of supporting three-dimensional tissue formation) cells planted onto the mosaic hydrogel sheets are precisely incorporated into the mosaic hydrogel sheet just at the time it's being created—generating the perfect conditions for cells to grow. _UToronto

This approach is likely to evolve rapidly to provide quick replacement tissues of a simpler nature, such as skin grafts. More complex tissues and organs will require sophisticated scaffolds, to allow the tissue to maintain shape and resist a variety of physical forces likely to come to bear in a variety of implant locations.

The fight against deadly diseases and ageing itself, must necessarily take on multiple forms. Humans have not, after all, conquered even the most rudimentary of enemies -- the virus. Despite our best efforts, we are still vulnerable to new outbreaks of emerging infectious diseases. And we will always be vulnerable to chance events such as accidents -- both terrestrial and cosmic.

But it is in the nature of our slightly advanced monkey selves to pursue our continued existence, as long as we can. h/t Brian Wang

New Experimental Drug Offers Hope for Early Stroke Treatment

Number of deaths for leading causes of death
Heart disease: 599,413
Cancer: 567,628
Chronic lower respiratory diseases: 137,353
Stroke (cerebrovascular diseases): 128,842
Accidents (unintentional injuries): 118,021
Alzheimer's disease: 79,003
Diabetes: 68,705
Influenza and Pneumonia: 53,692
Nephritis, nephrotic syndrome, and nephrosis: 48,935
Intentional self-harm (suicide): 36,909 _CDC US Leading Causes of Death

As shown above, stroke -- cerebrovascular accident (CVA) -- is the 4th ranking cause of death in the US. Besides mortality, there is also significant morbidity and disability associated with stroke worldwide.

Recent research at Toronto Western Hospital provides reason to hope for better drug treatments for stroke in the near future. The researchers tested a new type of drug -- a PSD-95 inhibitor -- in primates, in an acute stroke setting. Some of their results are pictured below.

A phase 2 clinical trial in humans was also recently completed in Ontario.

Nature

In a series of experiments, Michael Tymianski and colleagues at Toronto Western Hospital in Ontario, Canada, replicated the effects of stroke in macaques before intravenously administering a PSD-95 inhibitor, or a placebo. PSD-95 inhibitors interfere with the process that triggers cell death when the brain is deprived of oxygen.

To test its effectiveness the team used MRI to measure the volume of damaged brain for 30 days following the treatment, and conducted behavioural tests at various intervals within this time.

Monkeys treated with the PSD-95 inhibitor one hour after stroke had 55 per cent less damaged tissue in the brain after 24 hours and 70 per cent less after 30 days, compared with those that took a placebo. These animals also did better in behavioural tests. Importantly, the drug was also effective three hours after stroke.

...An early stage clinical trial in humans, run by firm NoNO in Ontario has also seen positive results. _NewScientist

Nature study abstract

PSD-95 Overview

PSD-95 complex as drug target for antidepressant development

The Role of PSD-95 and Cypin in Morphological Changes in Dendrites Following Sublethal NMDA Exposure Interesting abstract providing information on underlying factors involved.

This is a line of treatment which has been obvious for decades, but which has lacked the proper basic science backing up until now. Although PSD-95 inhibitors will not prevent all brain damage from occurring in stroke, nor will they restore damaged brain to normal function afterward, they do seem to limit the amount of damage that occurs, for each stroke.

It is a type of stop-gap measure, meant to prolong relative normal function as long as possible. More optimal developments for the future will involve better preventive measures and ways to rejuvenate damaged brain after the insult occurs. Full spectrum medical care will eventually involve all avenues of treatment, prevention, and restoration.