Scientists in Leeds have devised a new way to create the next generation of man-made molecules in a breakthrough that could revolutionise drug development.

Creating new drugs to combat disease and illness requires the completion of a complex 3D jigsaw. The shape of the drug must be right to allow it to bind to a specific disease-related protein and to work effectively, and this shape is determined by the core framework of the molecule.

Now a team from the Astbury Centre for Structural Molecular Biology at the University of Leeds has developed a new approach which allows the creation of molecules with an extraordinarily wide range of molecular frameworks and, hence, shapes. The new molecules are likely to have a wide range of biological functions, which means they could be valuable starting points for the discovery of new drugs.

Says lead researcher Professor Adam Nelson of the University’s School of Chemistry: “Nature has created hundreds of thousands of molecules that have different frameworks and biological purposes, but in the global pursuit of new drugs, chemists from around the world are racing to create new molecules with functions not seen in nature.”

The newly created molecules are being shared with colleagues in the Faculties of Biological Sciences and Medicine and Health to see if specific new molecular frameworks match the requirements of their own research.

Of the 30 million or so synthetic molecules made throughout the history of organic chemistry, many are based on an extremely small number of core frameworks, with the main differences being the groups attached at the periphery. “Making collections of similar molecules is great for optimising a biological property,” says Professor Nelson, “but to put it simply, if researchers need a cube-shaped molecule to target a particular protein, they may well find that they can only choose from libraries stocked with millions of sphere-shaped ones.”

Co-researcher Dr Stuart Warriner added: “Making molecules is a bit like making something using lego bricks. Up until now we’ve only really become good at making, say, the equivalent of a lego car or train. There might be 30 million synthetic molecules registered, but there’s probably several million of these that are the equivalent of lego cars they may have different wheels and wing mirrors, but their fundamental shape is essentially the same. We’ve not really scratched the surface of the possible structures that could be made. This lack of variety in the core shape of molecules may well limit the range of proteins that medicinal chemists can target.”

The Leeds approach makes use of ‘metathesis’, a reaction that won the 2005 Nobel Prize in Chemistry.

Explains Professor Nelson: “We take simple building blocks, a bit like the amino acids that make up peptides, and we assemble them in different sequences using three simple reactions to link them together in a chain. The key difference is that we then add the catalyst which initiates a ’scaffold reprogramming reaction’, which ripples down the chemical chain and restitches the molecule together in a completely different way each time.

“It’s a bit like a molecular square dance, where atoms in the molecule swap partners - and the exciting thing is that we can change the building blocks again and again in different combinations as a really powerful way to vary the core frameworks that result. The potential of this process is enormous,” he says.

The team from Leeds have used their approach to prepare molecules with 84 distinct molecular frameworks and about two-thirds of the frameworks are unprecedented in the history of organic chemistry. The work is a huge leap forward from landmark research reported in 2003, which resulted in the creation of six frameworks in a single process. It is also a significant improvement on more recent research in which around 30 frameworks were created using a complex combination of different reactions.

The team has deliberately chosen to prepare molecules with structural features that are similar to those found in natural products: “For example we know that putting oxygen atoms on every other carbon atom is something that frequently occurs in nature and has evolved for a useful purpose” says Professor Nelson. “We’re not aiming to improve on existing natural products or drugs - we want to create molecules with functions that nature’s not got round to making yet, or something that would only evolve naturally with new selection pressures that would make it beneficial for the organism.”

Work has already begun across campus to screen the molecules, which are already yielding “promising” results. The team are considering patenting molecules with novel biological functions.

Chemistry researchers at The University of Warwick and the John Innes Centre, have found a novel signalling molecule that could be a key that will open up hundreds of new antibiotics unlocking them from the DNA of the Streptomyces family of bacteria.

With bacterial resistance growing researchers are keen to uncover as many new antibiotics as possible. Some of the Streptomyces bacteria are already used industrially to produce current antibiotics and researchers have developed approaches to find and exploit new pathways for antibiotic production in the genome of the Streptomyces family. For many years it was thought that the relatively unstable butyrolactone compounds represented by “A-factor” were the only real signal for stimulating such pathways of possible antibiotic production but the Warwick and John Innes teams have now found a much more stable group of compounds that may have the potential to produce at least one new antibiotic compound from up to 50% of the 1000 or so known Streptomyces family of bacteria.

Colonies of bacteria such as Streptomyces naturally make antibiotics as a defence mechanism when those colonies are under stress and thus more susceptible to attack from other bacteria. The colonies need to produce a compound to spread a signal across the colony to start producing their natural antibiotic weapons.

The amounts of such signalling material produced are incredibly small. Only micrograms of these compounds can be isolated by Chemists and usually the available instrumentation needs at least milligrams of material to make a useful analysis. However the Warwick team was able to make use of the University of Warwick’s 700 MHz NMR machine to get a close look at just micrograms of 5 new possible signalling compounds identified as 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids (or AHFCAs).

The researchers, led by Dr Christophe Corre, and Professor Greg Challis from the University of Warwick’s Department of Chemistry were able to combine their new insight into these compounds with the relatively new full genetic sequences now available of some Streptomyces bacteria. They became convinced that the AHFCA group of compounds could play a role in stimulating the production of known and novel antibiotics. When they added AHFCAs to Streptomyces coelicolor W81 they were proved correct as it stimulated the production of methylenomycin antibiotics.

While the methylenomycins were already known as antibiotics, the researchers think it likely that novel pathways for antibiotic production are also under the control of AHFCAs. The AHFCAs should be relatively easy to make in significant quantity in a lab and could be used as a new tool for discovery of antibiotics. The researchers are now seeking funding to explore the AHFCAs and develop a novel approach for drug discovery. Introducing a variety of AHFCAs to various Streptomyces bacteria could activate hundreds of pathways for antibiotic production.

The lead researcher on the paper Dr Christophe Corre, from the University of Warwick’s Department of Chemistry said:

“Early results also suggest that this approach could switch on novel antibiotic production pathways in up to 50% of Streptomyces bacteria. With thousands of known members of the Streptomyces family that could mean that AHFCAs could unlock hundreds of new antibiotics to replenish our dwindling arsenal of effective antibiotic drugs.”

Tomatoes genetically modified to be rich in antioxidants called anthocyanins appeared to extend the life spans of cancer-prone mice, a European study finds.

The modified tomatoes were created by adding two genes (Delila and Rosea1) from the snapdragon flower. The anthocyanins, which belong to the flavonoid class of antioxidants, gave the tomatoes a peculiar purple color.

“The two genes we have isolated are responsible for flower pigmentation and, when introduced in other plants, turned out to be the perfect combination to produce anthocyanins, the same phytochemical found in blueberries,” study author Eugenio Butelli, of the FLORA project, said in a news release.

Chemical tests revealed that the “purple tomato has a very high antioxidant activity, almost tripled in comparison to the natural fruit,” making it very useful to study the effect of anthocyanins, Butelli said.

The researchers fed a powder obtained from the purple tomatoes to mice that lacked the p53 gene, which helps protect against cancer. These mice had an average life span of 182 days compared to 142 days for p53-deficient mice fed a standard diet.

The findings were published in the Oct. 26 issue of  Nature Biotechnology.

The study authors emphasized this is a preliminary study, and much more research needs to be done before there’s any possibility of human trials.

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Rocky Mountain Down Syndrome Educational Fund supports University of Denver study

Researchers at the University of Denver (DU) Morgridge College of Education are conducting a groundbreaking study that will compare two early literacy intervention approaches to educating young children with Down syndrome. The Rocky Mountain Down Syndrome Educational Fund is funding the study, which hopes to improve teaching methods for children with the condition.

Researchers are seeking children in the Denver area, ages 2 1/2 to 5, to participate in the study, which will involve a two-day training session to be held at DU followed by an at-home intervention program in which parents will implement the program with their child for approximately 15 minutes per day for approximately 10 months. There is no cost to participate. Contact Staci Jordan at (303) 871-3465 for information on how children can be enrolled.

“There has been little to no research on how our children with Down syndrome learn, especially regarding reading and language,” says Michelle Sie Whitten, executive director of the Anna and John J. Sie Foundation and Advisory Committee Chair of The Rocky Mountain Down Syndrome Educational Fund. “There have been significant breakthroughs in terms of how children with other developmental disabilities learn, and I strongly believe that our kids deserve the same attention.”

The result of this pilot study, Whitten said, could have a profound effect on the academic achievement of children with Down syndrome. An international team of experts has contributed to the study, including Sue Buckley, a chartered psychologist in England with more than 30 years of experience in the field of developmental disabilities.

“What is so exciting and unique about this particular study is that scientifically based research on early learning intervention has been translated into applied research in areas such as autism, but never before in Down syndrome research,” says Karen Riley, assistant professor of Child, Family and School Psychology at DU, and the key investigator driving the pilot study. “In addition, we are attracting researchers for this study who have expertise in other developmental disabilities, and we are applying their knowledge to Down syndrome.”

This study was initiated by The Rocky Mountain Down Syndrome Educational Fund. It is underwritten by a $130,000 gift from The Rocky Mountain Down Syndrome Educational Fund, $10,000 from the McDonnell Foundation and $10,000 from the University of Denver. The researchers working on this study have been trained by Buckley, who is one of the world’s leading researchers in the education and development of children with Down syndrome.

Researchers have reported positive results from a safety and efficacy study pertaining to tribendimidine, a broad-based treatment for intestinal worm infections. The group’s results demonstrate the success of the new drug from China versus that of the standard albendazole for the treatment of hookworm, large roundworm, whipworm, and, for the first time, threadworm and tapeworm. The study was jointly implemented by researchers from the Swiss Tropical Institute in Basel, the National Institute of Parasitic Diseases (IPD) in Shanghai, the Yunnan Institute of Parasitic Diseases in Simao, China, and the Jiangsu Institute of Parasitic Diseases in Wuxi, China. Details are published October 15th in the open-access journal PLoS Neglected Tropical Diseases.

Globally, more than one billion people are infected with intestinal worms. These chronic infections negatively impact on child and maternal health, nutritional status, physical performance, and cognitive development. The current control strategy relies on drugs to reduce morbidity, ideally complemented by the provision of safe water and sanitation to curb transmission. Only four drugs are currently recommended by the World Health Organization for treating soil-transmitted helminth infections, making the potential development of drug resistance a concern. Tribendimidine belongs to a different chemical class than current worm treatments. The drug had been developed at IPD and Shandong Xinhua Pharmaceutical in Zibo, China, and was approved by the China State Food and Drug Administration in 2004.

The community-based study involved 123 individuals who were screened for intestinal helminth infections, and randomly allocated to tribendimidine or the widely used albendazole treatment (both at 200 mg for children aged 5-14 years and 400 mg for individuals aged 15 years and above). The researchers’ administration of a single oral dose of tribendimidine cured up to 92% of the common soil-transmitted helminth infections in humans in a highly endemic setting in China. Encouraging results were also found against threadworm and tapeworm infections. After treatment, these two parasites were absent in 55% and 67% of those initially infected, respectively. The infection intensity of large roundworms and hookworms was significantly reduced by both drugs, and no adverse treatment-related events were noted among the final study cohort.

The obtained results need to be validated in larger patient cohorts and different epidemiological settings, and repeated dosing should be tested to further improve treatment outcomes.

THE PUBLISHED ARTICLE CAN BE FOUND AT: http://dx.plos.org/10.1371/journal.pntd.0000322

Tests of medication used to treat high blood pressure suggest positive role in potential plaque regression

Research presented at the 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation (CRF), suggests that olmesartan, a drug commonly used to treat high blood pressure, may play a role in reducing coronary plaque.

The trial, “Impact of OLmesartan on progression of coronary atherosclerosis; evaluation by IVUS [OLIVUS], was performed on 247 angina patients with native coronary artery lesions. Patients were randomly assigned to receive 20-40mg/day of olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, diuretics, nitrates, glycemic control agents and/or statins per physician’s guidance.

Serial Intravenous Ultrasound (IVUS) examinations were performed to assess the amount of coronary plaque before and 14 months after the start of treatment.

At the start of the trial, patient characteristics and all IVUS measurements were identical between the two groups. However, after 14 months of treatment, IVUS showed significant decreases in measurements of plaque volume in the olmesartan group, despite similar blood pressure readings.

In addition, multivariate analysis identified olmesartan administration as one of the factors that caused the decrease in plaque volume.

“Management of plaque is a key front in the war on sudden heart attack,” said Atsushi Hirohata, M.D, Ph.D, Cardiovascular Medicine, the Sakakibara Heart Institute of Okayama, Okayama, Japan and lead author of the study. “These results suggest a positive role in potential plaque regression through the administration of olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.”

In a groundbreaking study led by an eminent molecular biologist at Florida State University, researchers have discovered that as embryonic stem cells turn into different cell types, there are dramatic corresponding changes to the order in which DNA is replicated and reorganized.
The findings bridge a critical knowledge gap for stem cell biologists, enabling them to better understand the enormously complex process by which DNA is repackaged during differentiation — when embryonic stem cells, jacks of all cellular trades, lose their anything-goes attitude and become masters of specialized functions.

As a result, scientists now are one significant step closer to the central goal of stem cell therapy, which is to successfully convert adult tissue back to an embryo-like state so that it can be used to regenerate or replace damaged tissue. Such therapies hold out hope of treatments or cures for cancer, Parkinson’s disease, multiple sclerosis, spinal cord injuries and a host of other devastating disorders.

In mammalian nuclei, replication takes place at punctate sites or foci. Early-replicating foci localize to the interior of the nucleus (green), while the periphery of the nucleus and nucleoli harbor… Click here for more information.

Using mouse and human embryonic stem cells, FSU researchers employed advanced imaging techniques and state-of-the-art genomics technology to demonstrate, with unprecedented resolution along long stretches of chromosomes, which sequences are replicated first, and which occur later in the process of differentiation.

“Understanding how replication works during embryonic stem cell differentiation gives us a molecular handle on how information is packaged in different types of cells in manners characteristic to each cell type,” said David M. Gilbert, the study’s principal investigator. “That handle will help us reverse the process in order to engineer different types of cells for use in disease therapies.” Internationally renowned for his body of cutting-edge research on chromosomal structure and reproduction that he began as a doctoral student at Stanford University in the 1980’s, Gilbert joined the FSU faculty and was appointed as the first J. Herbert Taylor Distinguished Professor of Molecular Biology in 2006.

Results from the FSU study, which includes contributions from researchers at three other institutions, are described in a paper published in the October 7, 2008, edition of PLoS Biology, a peer-reviewed journal that showcases biological science research of exceptional significance. So prodigious were the findings that the current paper — “Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation” — is focused solely on results observed in the mouse embryonic stems cells; data on the human cells will be detailed in a future report.

“We know that all the information (DNA) required to take on the identity of any tissue type is present in every cell, because we already can, albeit very inefficiently, create whole animals from adult

tissue through cloning,” Gilbert said. “We also can make a kind of artificial embryonic stem cells, called induced pluripotent stem cells, out of many adult cell types, but there are two major hurdles remaining. First, the methods currently used rely on the unnatural retroviral insertion of genes into patients’ cells, and these genes are capable of forming tumors. Second, this method is very inefficient as well because only one in 1,000 cells into which the genes are inserted becomes pluripotent. We must learn how cells lose pluripotency in the first place so we can do a better job of reversing the process without risks to patients.

“The challenge is, adult cells are highly specialized and over the course of their family history over many generations they’ve made decisions to be certain cell types rather than others,” he said. “In doing so, they have tucked away the information they no longer need on how to become other cell types. Hence, all cells contain the same genetic information in their DNA, but during differentiation they package it with proteins into ‘chromatin’ in characteristic ways that define each cell type. The rules that determine how cells package DNA are complicated and have been difficult for scientists to decipher.”

But, Gilbert noted, one time that the cell “shows its cards” is during DNA replication.

“During this process, which was the focus of our FSU research, it’s not just the DNA that replicates,” he said. “All the packaging must be replicated as well in each cell division cycle.”

He explained that embryonic stem cells have many more, smaller “domains” of organization than differentiated cells, and it is during differentiation that they consolidate information.

“In fact, ‘domain consolidation’ is what we call the novel concept we discovered,” he said.

Gilbert likened the concept of domain consolidation to the undeclared or “undifferentiated” college student who then consolidates her literature resources during the course of declaring a major and specialization. “From a student with books on all subjects on all of her bookshelves comes a student who has placed all texts pertaining to her major on the eye-level shelf and moved the distantly-related, potentially distracting texts to the hard-to-reach bottom or top shelves,” he said.

“Now, our challenge as scientists,” said Gilbert, “is to build on what we’ve learned about domain consolidation so that we can efficiently and safely create patient-specific induced pluripotent stem cells or even coax the body’s cells to change their specialization in response to medications.”

In the advance online edition of Nature Medicine, scientists from Sainte-Justine Hospital Research Center, the Université de Montréal and the Institut national de la santé et de la recherche médicale (INSERM) in France report how the GPR91 receptor contributes to activate unchecked vascular growth that causes vision loss in common blinding diseases. These findings could also have wide-ranging and positive implications for brain tissue regeneration.

While investigating the molecular mechanisms that lead to vision loss, the research team uncovered that the GPR91 receptor can mediate irregular vascular growth that is responsible for some of the main causes of blindness in the industrial world: retinopathy of prematurity in infants, diabetic retinopathy in adults (vision loss or blindness that affects up to 90 percent of diabetics) or age-related macular degeneration in seniors (central vision loss).

“We found that GPR91 is a master regulator of blood vessel growth, which upon enhanced activation leads to the unchecked and anarchic proliferation of vascular networks, which is the hallmark of retinopathies. This uncontrolled overgrowth can ultimately cause the retina to detach and a person to lose their sight,” says Dr. Mike Przemyslaw Sapieha, the study’s lead author and a scientist at the Sainte-Justine Hospital Reserch Center and the Université de Montréal.

“With the identification of GPR91 as a key player in this disease process, we can move forward in designing treatments that block the receptor and consequently stop vision loss,” adds Dr. Sapieha. “Inhibition of GPR91 has a great therapeutic potential to halt these blinding diseases.”

GPR91 to preserve neurons

The team’s study also provides promise that the GPR91 receptor could preserve neurons. “Neurons are key sensors in retina oxygenation and serve as key players in the repair process of the retina,” explains Dr. Sylvain Chemtob, director of the study and a neonatal researcher at the Sainte-Justine Hospital Research Center and professor at the Université de Montréal’s Department of Pediatrics, Ophthalmology, Pharmacology and the School of Optometry.

“Given the similarities between the retina and the brain, we can envisage applying our findings in retina to the brain,” says Dr. Chemtob. “Activation of the GPR91 receptor could be beneficial in helping salvage neurons in damaged brain tissue in stroke or head injury victims.”

GPR91 to stop cancer growth

This study is the first to examine the wide-ranging implications of GPR91 and to investigate how the receptor, which is present in neurons, responds to stresses and adjust when in its oxygenation state is compromised. “This is a new concept in vascular biology,” says Dr. Sapieha, noting it is conceivable that interfering with the GPR91 receptor could be used to stop cancer growth. “If you stop GPR91 from allowing blood vessels to expand and supply a tumour with nutrients and oxygen, one can significantly hamper growth of the cancer.”

While these promising investigations on GPR91 were conducted in animals, the receptor is also found in humans, and Dr. Chemtob surmises that extension of the research to human clinical investigations could be in three to fours years. “We expect these findings to have an enormous impact,” he says.

This study was funded through grants from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Quebec, the Fonds de la recherche en santé du Québec, the Heart and Stroke Foundation of Canada, the March of Dimes Birth Defects Foundation, the Robert A. Welch Foundation and the Foundation Fighting Blindness.

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To understand where fat comes from, you have to start with a skinny mouse. By using such a creature, and observing the growth of fat after injections of different kinds of immature cells, scientists at the Howard Hughes Medical Institute and Rockefeller University have discovered an important fat precursor cell that may in time explain how changes in the numbers of fat cells might increase and lead to obesity. The finding, published online in this week’s issue of the journal Cell, could also have implications for understanding how fat cells affect conditions such as diabetes and cardiovascular disease.

“The identification of white adipocyte progenitor cells provides a means for identifying factors that regulate the proliferation and differentiation of fat cells,” says senior author Jeffrey Friedman, who is the Marilyn M. Simpson Professor at Rockefeller and a Howard Hughes Medical Institute investigator.

Obesity, a major public health problem in the United States and increasingly in much of the Western world, results, in part, from an increase in the mass and number of white fat cells. Because white fat cells are post-mitotic, meaning that they cannot divide, scientists have hypothesized that a population of fat precursor cells must exist in the fat depot in order to produce new fat cells. But identifying these fat precursor cells has been difficult.

With the assistance of researchers in Rockefeller’s Flow Cytometry Resource Center, first author Matt Rodeheffer, a postdoctoral associate in Friedman’s Laboratory of Molecular Genetics, used a cell sorting technique called fluorescence-activated cell sorting, or FACS, to search for cell populations that could produce fat in cell cultures and identified two such populations.

To determine if these cells could develop into fat cells in living animals, Rodeheffer injected these cell populations into the fat depots of a genetically engineered mouse, developed at NIH, called fatless, which lacks white fat and mimics a condition in humans called lipodystrophy that also results in diabetes.

Rodeheffer found that only one of the isolated cell populations, which express the CD24 cell-surface marker protein, produced fat tissue in the fatless mouse. This population normally represents only .08 percent of the non-adipocyte population in adipose tissue.

An imaging assay recently developed by co-author Kivanç Birsoy, a graduate student in Friedman’s laboratory, enabled Rodeheffer to observe the CD24-expressing cells form fat in a living animal. Birsoy’s technique uses another animal strain called the leptin-luciferase mouse, in which the visibly detectable marker luciferase is expressed under the control of the promoter of the gene that produces the hormone leptin. In this mouse strain the luciferase marker gene only switches on in mature fat cells, and provides a non-invasive way of watching immature fat cell precursors develop into mature fat cells in a living animal over time.

“I injected the CD24+ cells - which represent a very small population of cells in normal adipose tissue - into a site where the fat would normally develop in the fatless mouse, and I found that a normal sized fat depot forms at the site of injection,” says Rodeheffer.

Rodeheffer also found that the injection of the fat-producing cells corrects the fatless mouse’s diabetes, and the fat cells secrete adipocyte-specific signaling proteins called cytokines. Both of these results confirm that the cells produced in the fatless mouse are functional fat cells.

“This finding gives us a better understanding of the basic biology of adipose tissue and opens the door for us and for other researchers to be able to study these cells in living animals and determine the molecular factors that regulate formation of adipose tissue,” says Rodeheffer. “We then can potentially study how the growth and differentiation of these cells are regulated in obesity and determine whether or not the molecular events that are involved in the regulation of adipose tissue are contributing factors to other pathologies, such as diabetes and cardiovascular disease, that are associated with obesity and metabolic syndrome.”

Surgeons at Cedars-Sinai Medical Center’s Institute for Spinal Disorders have combined three innovative minimally invasive spine surgery procedures to treat spinal curvature in adults, a common consequence of aging. An article in the October issue of the Journal of Spinal Disorders and Techniques is believed to be the first to document the use of these procedures in combination to correct this condition, known as adult lumbar degenerative scoliosis.

“Many patients suffering from degenerative scoliosis are elderly and have coexisting medical problems that make them poor candidates for traditional surgery and a long recovery process. But as a result of three new technologies and minimally invasive approaches, we are able to offer patients who otherwise might not be candidates for surgery, a solution that is safe and provides very good results,” said orthopaedic surgeon Neel Anand, M.D., Mch. Orth, director of Orthopaedic Spine Surgery at Cedars-Sinai.

Anand said lumbar degeneration and curvature can be caused simply by the wear and tear of aging. Discs – the cushions and spacers between vertebrae – wear down and collapse, allowing the spine to shift out of alignment. In other cases, minor scoliosis that may have existed since childhood becomes more pronounced with age. In either situation, pain is the primary complaint.

The article reviews 12 cases of Anand’s. These cases were examined as part of a retrospective chart review for patients who underwent these techniques as part of standard care. Patients were 50 to 85 years old, with an average age of about 73. Each had undergone extensive conservative treatment, such as medical management and physical therapy, without long-term success. Curvature resulted from the degeneration of multiple discs, ranging from two to eight segments of the spine.

The first stage of the two- to three-step correction procedure was performed through small incisions in the patient’s side, working through a tube to access the front of the spine. Using either of two systems – the XLIF® (Extreme Lateral Interbody Fusion) or the DLIF® (Direct Lateral Interbody Fusion) – Anand cleared out damaged disc material and replaced it with spacers filled with bone and a protein that promotes fusion.

“We used to access the front of the spine through the abdomen. The biggest advantage of going in from the side is that we no longer have to work around the organs and large blood vessels of the abdomen. We work through a very safe corridor to get to the discs in question. We go in and correct each disc that has collapsed, like building a skyscraper. As we put in spacers from the bottom up, we get considerable correction, just from doing the lateral approach, the first stage,” Anand said.

The second step was needed only for patients whose scoliosis affected the area between the lower end of the lumbar spine and the top of the sacral spine (the lumbar 5 and sacral 1 vertebrae), which cannot be accessed from the side because of the location of the pelvic bone. In these cases, the area was accessed from below, using the AxiaLIF® procedure, which allows the L5-S1 disc to be secured with a solid, sturdy screw.

The final stage, performed two or three days after the first, was the placement of rods on either side of the spine. This was accomplished with the use of the CD Horizon Longitude system and special high-tech screws.

“The third technology making this correction possible for these patients is the percutaneous screw that can be placed through small nicks in the skin. Using fluoroscopic guidance, we’re able to place the screws into the vertebral bodies and pass the rods through the skin into position. We then connect the rods to the screws and get further correction of the curve,” Anand said.

Anand, first author of the journal article, is a paid consultant with the three companies that market the instrumentation and techniques. Because he was involved in the development of the percutaneous screws, he receives royalties from the manufacturer when the devices are used elsewhere, but he receives no royalties on any cases performed at Cedars-Sinai.

“With traditional surgical procedures and large incisions, patients would have to spend time after surgery in the intensive care unit for monitoring and blood transfusions, and there would be months of recuperation,” said Anand. “With the new technologies and minimally invasive techniques, we lose very little blood and patients are back on a regular surgical nursing unit in about an hour. And instead of going through six months or more of painful, restricted recuperation, recovery time is much shorter and more comfortable. We’re achieving the same correction but through different, smaller, safer portals of entry.”