So, do we have anyone in stroke with two functioning neurons that can look at this and suggest using it for stroke? NO, WE DON'T! Nothing will be done; there is NO leadership or strategy anywhere in stroke! Just plan on never having a stroke!
After single injection, paralyzed animals regained ability to walk within four weeks
Northwestern University researchers have developed a new injectable
therapy that harnesses “dancing molecules” to reverse paralysis and
repair tissue after severe spinal cord injuries.
In a new study,
researchers administered a single injection to tissues surrounding the
spinal cords of paralyzed mice. Just four weeks later, the animals
regained the ability to walk.
Five key developments
By sending bioactive signals to trigger cells to repair and
regenerate, the breakthrough therapy dramatically improved severely
injured spinal cords in five key ways:
- The severed extensions of neurons, called axons, regenerated
- Scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished
- Myelin, the insulating layer of axons that is important in transmitting electrical signals efficiently, reformed around cells(We need this)
- Functional blood vessels formed to deliver nutrients to cells at the injury site(We need this)
- More motor neurons survived
After the therapy performs its function, the materials biodegrade
into nutrients for the cells within 12 weeks and then completely
disappear from the body without noticeable side effects. This is the
first study in which researchers controlled the collective motion of
molecules through changes in chemical structure to increase a
therapeutic’s efficacy.
“Our research aims to find a therapy that can prevent individuals
from becoming paralyzed after major trauma or disease,” said
Northwestern’s Samuel I. Stupp,
who led the study. “For decades, this has remained a major challenge
for scientists because our body’s central nervous system, which includes
the brain and spinal cord, does not have any significant capacity to
repair itself after injury or after the onset of a degenerative disease.
We are going straight to the FDA to start the process of getting this
new therapy approved for use in human patients, who currently have very
few treatment options.”
Stupp is Board of Trustees Professor of Materials Science and
Engineering, Chemistry, Medicine and Biomedical Engineering at
Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology (SQI) and its affiliated research center, the Center for Regenerative Nanomedicine. He has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine.
Life expectancy has not improved since the 1980s
According to the National Spinal Cord Injury Statistical Center,
nearly 300,000 people are currently living with a spinal cord injury in
the United States. Life for these patients can be extraordinarily
difficult. Less than 3% of people with complete injury ever recover
basic physical functions. And approximately 30% are re-hospitalized at
least once during any given year after the initial injury, costing
millions of dollars in average lifetime health care costs per patient.
Life expectancy for people with spinal cord injuries is significantly
lower than people without spinal cord injuries and has not improved
since the 1980s.
“Currently, there are no therapeutics that trigger spinal cord
regeneration,” said Stupp, an expert in regenerative medicine. “I wanted
to make a difference on the outcomes of spinal cord injury and to
tackle this problem, given the tremendous impact it could have on the
lives of patients. Also, new science to address spinal cord injury could
have impact on strategies for neurodegenerative diseases and stroke.”
‘Dancing molecules’ hit moving targets
The secret behind Stupp’s new breakthrough therapeutic is tuning the
motion of molecules, so they can find and properly engage constantly
moving cellular receptors. Injected as a liquid, the therapy immediately
gels into a complex network of nanofibers that mimic the extracellular
matrix of the spinal cord. By matching the matrix’s structure, mimicking
the motion of biological molecules and incorporating signals for
receptors, the synthetic materials are able to communicate with cells.
“Receptors in neurons and other cells constantly move around,” Stupp
said. “The key innovation in our research, which has never been done
before, is to control the collective motion of more than 100,000
molecules within our nanofibers. By making the molecules move, ‘dance’
or even leap temporarily out of these structures, known as
supramolecular polymers, they are able to connect more effectively with
receptors.”
Stupp and his team found that fine-tuning the molecules’ motion
within the nanofiber network to make them more agile resulted in greater
therapeutic efficacy in paralyzed mice. They also confirmed that
formulations of their therapy with enhanced molecular motion performed
better during in vitro tests with human cells, indicating increased
bioactivity and cellular signaling.
“Given that cells themselves and their receptors are in constant
motion, you can imagine that molecules moving more rapidly would
encounter these receptors more often,” Stupp said. “If the molecules are
sluggish and not as ‘social,’ they may never come into contact with the
cells.”
Signals mimic natural proteins
Once connected to the receptors, the moving molecules trigger two
cascading signals, both of which are critical to spinal cord repair. One
signal prompts the long tails of neurons in the spinal cord, called
axons, to regenerate. Similar to electrical cables, axons send signals
between the brain and the rest of the body. Severing or damaging axons
can result in the loss of feeling in the body or even paralysis.
Repairing axons, on the other hand, increases communication between the
body and brain.
The second signal helps neurons survive after injury because it
causes other cell types to proliferate, promoting the regrowth of lost
blood vessels that feed neurons and critical cells for tissue repair.
The therapy also induces myelin to rebuild around axons and reduces
glial scarring, which acts as a physical barrier that prevents the
spinal cord from healing.
“The signals used in the study mimic the natural proteins that are
needed to induce the desired biological responses. However, proteins
have extremely short half-lives and are expensive to produce,” said
Zaida Álvarez, the study’s first author and former research assistant
professor in Stupp’s laboratory. “Our synthetic signals are short,
modified peptides that — when bonded together by the thousands — will
survive for weeks to deliver bioactivity. The end result is a therapy
that is less expensive to produce and lasts much longer.”
Universal application
While the new therapy could be used to prevent paralysis after major
trauma (automobile accidents, falls, sports accidents and gunshot
wounds) as well as from diseases, Stupp believes the underlying
discovery — that “supramolecular motion” is a key factor in bioactivity —
can be applied to other therapies and targets.
“The central nervous system tissues we have successfully regenerated
in the injured spinal cord are similar to those in the brain affected by
stroke and neurodegenerative diseases, such as ALS, Parkinson’s disease
and Alzheimer’s disease,” Stupp said. “Beyond that, our fundamental
discovery about controlling the motion of molecular assemblies to
enhance cell signaling could be applied universally across biomedical
targets.”
Other Northwestern study authors include
Evangelos Kiskinis,
assistant professor of neurology and neuroscience in Feinberg; research
technician Feng Chen; postdoctoral researchers Ivan Sasselli, Alberto
Ortega and Zois Syrgiannis; and graduate students Alexandra
Kolberg-Edelbrock, Ruomeng Qiu and Stacey Chin. Peter Mirau of the Air
Force Research Laboratories and Steven Weigand of Argonne National
Laboratory also are co-authors.
