Taking the Shots out of Orthopedic Surgery

As anyone who’s had knee or hip replacement surgery knows, post-op recovery can be long and painful. There’s the learning to walk again, the physical therapy and the dreaded daily injections in the belly.

While great strides have been made in surgery for degenerative joint disease, preventing post-op complications such as deep vein thrombosis (DVT) and pulmonary embolism (PE) remains problematic. Conventional antithrombotic agents (heparin and low-molecular-weight heparin) have to be given by injection into fatty subcutaneous tissue, usually into the leg or abdomen, for days or weeks after surgery and discharge from the hospital. Not surprisingly, acceptance of, and compliance with, thromboembolic prophylaxis is limited by the need for injections, the bruising and associated risks for bleeding.

Now it seems the days are numbered for injection therapy.  A recent meta-analysis of 22 randomized trials comparing oral factor Xa inhibitors with low-molecular-weight heparin injections in adults who underwent total hip or knee replacement has just been published in the Annals of Internal Medicine.

The results showed that new generation oral antithrombotic agents, including apixaban, edoxaban, and rivaroxaban, that do not require monitoring, actually led to fewer symptomatic deep venous thrombosis.

Furthermore, there was no difference between the groups in terms of mortality, non-fatal PE, major bleeding, or bleeding leading to reoperation. The study authors therefore predict that these oral agents will likely replace low-molecular-weight heparins.

As a likely candidate for future joint replacement, thanks to a family history of osteoarthritis, and joints wrecked by years of gymnastics and running, I for one am very grateful.

Diabetes Drug may Repair Injured Brains

Here’s a good brain teaser for a Wednesday.  What do an old diabetes drug, brain injury and Alzheimer’s Disease have in common?

Here’s some clues to help you solve the riddle.

(i)           Metformin is a widely used treatment for type II diabetes

(ii)          An increasing proportion of people with Alzheimer’s Disease also have diabetes

(iii)         Hyperinsulinemia (excess levels of insulin in the blood) may enhance the onset and progression of neurodegeneration

Have you solved it?  If so, congratulations!

If not, the answer, according to data just published in the journal Cell Stem Cell is that the former may hold the clue to treating the latter.

In other words, the study suggests that metformin, an anti-diabetes drug first discovered in the 1920’s, is able to help activate the mechanism that signals stem cells to generate brain cells.

Principal investigator, Freda Miller, a Professor from the Department of Molecular Genetics at the University of Toronto
says “If you could take stem cells that normally reside in our brains and somehow use drugs to recruit them into becoming appropriate neural cell types, then you may be able to promote repair and recovery in at least some of the many brain disorders and injuries for which we currently have no treatment.”

The research involved laboratory experiments using both mouse and human brain stem cells, as well as learning and memory tests performed on live mice given the drug.

Miller and her colleagues started by adding metformin to stem cells from the brains of mice, then repeated the experiment with human brain stem cells generated in the lab. In both cases, the stem cells gave rise to new brain cells.

They then tested the drug in lab mice and found that those given daily doses of metformin for two or three weeks had increased brain cell growth and outperformed rodents not given the drug in learning and memory tasks.

In the key experiment, mice were forced to learn the position of a platform hidden under the surface of a water-filled maze and then asked rapidly to learn a new position.

Mice were injected with either metformin or saline for 38 days. On days 22 through 38, they learned the initial position of the platform, which provided an escape from the water-filled maze.  Then the platform was moved to the opposite side of the maze, and the animals were asked again to learn its position. In both tasks, the mice learned the platform positions with equivalent speed.

But when they were put back in the maze – this time with the platform removed – control mice spent more time searching for it in the original position, while the metformin-treated animals preferentially looked in the new region.

The implication  is that metformin helped the mice form their new memories of the second platform position. Further analysis showed that their enhanced ability was paralleled by an increase in the number of  neurons.

In a separate study researchers have shown that metformin can increase lifespan and delay the onset of cognitive impairment in a mouse model of Huntington’s disease.

Taken together, these findings raise the possibility that metformin’s ability to enhance neurogenesis might have a positive impact in some nervous system disorders.

Miller’s team is already planning a pilot study to test metformin in young patients with acquired brain damage, either as result of treating a childhood brain tumor or from a traumatic head injury.

We will report back to you with results, as they are published.

The Tangled Webs We Weave

Growing fresh blood vessels is a much fantasized goal of biomedical engineers. It’s probably also a fantasy of dialysis patients, hemophiliacs and others with medical conditions that necessitate regular venipuncture and whose veins are a mess from being breached several times a week.

To date, most approaches for growing blood vessels have involved coaxing human cells, either from donors or the patient themselves to manufacture connective tissue. One of the biggest challenges however has been to make the tissues develop into vein shaped vessels.  Some researchers have started with flat sheets of this tissue which they then roll into tubes. Others have used tubular molds. Typically, however, the scaffolding is eventually destroyed by the body’s immune system.

Now one company –  Cytograft Tissue Engineering, is trying a technique that made us look twice. They’re weaving the vessels from human thread that’s been created by spinning thin strips of cultured connective tissue.

The hope is that these woven structures could be easier to mass-produce than the tubes made with other techniques.

A long time ago we decided we were going to make strong tissues without any scaffolding,” says Nicolas L’Heureux, Cytograft’s cofounder and chief scientific officer. “Once you get it in the body, your body doesn’t see it as foreign.”

The company developed the “human textile” idea from earlier work using sheets of biological material to reconstruct blood vessels. Researchers grow the human skin cells in a flask under conditions that encourage the cells to lay down a sheet of extracellular matrix – a structural material that makes up connective tissue. They then harvest the sheets from the culture flasks and then slice the sheets into thin ribbons that can be spooled into threads which can be used by automated weaving and braiding machines to create three-dimensional structures that do not require fusing.

Weaving 48 strands of human connective tissue into a tube

Creating textiles is an ancient and powerful technique, and combining it with biomaterials is exciting because it has so much more versatility than the sheet method,” says Christopher Breuer, a surgeon, scientist, and tissue engineer at the Yale School of Medicine. “The notion of making blood vessels or more complex shapes like heart valves, or patches for the heart, is much easier to do with fibers. There is no limit to the size or shapes that you can make.”

In other words, the biological strands could be used to weave blood vessels, patches and grafts that a patient’s body would readily accept for almost any kind of wound repair or reconstruction.

Cytograft has not yet tested its woven blood vessels in humans, but preclinical dog work has shown that the grafts are resistant to puncture damage and that very little blood leaks from the weave.

Furthermore, the implants remain intact after months. That’s partly because Cytograft’s implants contain no cells. Though the company’s earlier implants were made of extracellular matrix produced from a patient’s own cells, they now harvest the material from cells unrelated to the person receiving the graft and remove the “donor” cells completely. Without any foreign cells to trigger an  immune response blood vessels can be produced ahead of time for use in any patient.

The company is also working on a technique in which the cell-produced sheets are processed into particles instead of threads. Molding the particles together could eventually produce a liver, pancreas, or kidney.

Health or horror? Let us know what you think.

Spinal Cord Injury therapy – one small step closer

Back in August 2010, Word on Health brought you news that the FDA had given the green light for a stem cell therapy trial.

Given the enormous ethical and regulatory hurdles surrounding this controversial topic, we take our hats off to Geron Corporation who, on Monday, announced the enrolment of the first patient.

The primary objective of the Phase I study is to assess the safety and tolerability of the stem-cell therapy GRNOPC1 in patients with recent thoracic spinal cord injuries. The therapy is injected directly into the injured area and is hoped to restore spinal-cord function by triggering the production of myelin-producing cells, potentially allowing for new movement.

Spinal Cord Injury is caused by trauma to the spinal cord that results in loss of functions such as movement, sensation and bowel or bladder control. Every year approximately 12,000 people in the U.S. sustain spinal cord injuries. The most common causes are automobile accidents, falls, gunshot wounds and sports injuries.

The initiation of this Phase I study is thought to represent the first publicly known use of embryonic stem cells in humans.

According to Geron’s President and CEO, Thomas B. Okarma, Ph.D., M.D. “Initiating the GRNOPC1 clinical trial is a milestone for the field of human embryonic stem cell-based therapies. When we started working on this in 1999, many predicted that it would be a number of decades before a cell therapy would be approved for human clinical trials.”

In order to participate in the study, patients must be newly injured and receive the therapy within 14 days of the injury. The company has said it plans to enroll between eight and 10 patients in the US.

The trial is expected to take about two years to complete. Word on Health will be watching closely and will bring you further news as it breaks.  In the meantime we’d love to hear from you about your thoughts on this.

21st Century Medicine promises new cures

More than 400 leaders in the field of regenerative medicine from across the world gathered last week in North Carolina at the 1st annual Translational Regenerative Medicine Forum.

Regenerative Medicine focuses on:

·         Medical devices and artificial organs

·        Tissue engineering and biomaterials

·         Cellular Therapies

·         Clinical Translation

The meeting covered best practices and business models to bring new therapies to patients Speakers also discussed the challenges of this emerging medical field, including obtaining funding. Robert N. Klein, of the California Institute for Regenerative Medicine, talked about that state’s successful referendum to fund stem cell research with state-issued bonds. He compared state investment in scientific research to investment in roads and other infrastructure. “We are used to funding physical capital. We have to realize that in the 21st century it is appropriate to fund intellectual capital.”

Andrew von Eschenbach, M.D., of the Center for Health Transformation, said that the promise of regenerative medicine demands a paradigm shift from treating disease to restoring health.

Although this may sound like a distant dream a lot of research is being undertaken.

“Regeneration is one of our top priorities,” said Alan Lewis, Ph.D., President and CEO of the Juvenile Diabetes Research Foundation International, “the organization has invested $60 million in the past few years on research to regenerate islet cells, the cells in the pancreas that produce insulin”.

Col. Janet R. Harris, Ph.D., M.S.N., from the U.S. Army Medical Research and Materiel Command, talked about a $85 million federally funded project to apply the science of regenerative medicine to battlefield injuries. “We’ve been very pleased with the progress we’re seeing,” she said. “Only two years into the grant, 13 clinical trials are being funded.”

Word on Health wonders which will come first, the Six Billion Dollar Man or the Bionic Woman?!?

We invite you to have your say.