Ugly traffic islands prompt call for action

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Sept. 30, 2014, 9:10 p.m.

A BALLARAT resident is calling for two asphalted traffic islands in the heart of the city to be grassed.

Unsympathetic to heritage: Ballarat resident Brian Pola at the unsightly traffic islands. PICTURE: ADAM TRAFFORD

A BALLARAT resident is calling for two asphalted traffic islands in the heart of the city to be grassed.

Ballarat resident Brian Pola dubbed the asphalted traffic islands, situated in front of a heritage-listed 1860s cottage in Armstrong Street South, as unsightly.

The council recently cut four holes into the asphalted islands to plant trees, but Mr Pola said it would have been easier and less expensive to completely remove the asphalt and grass the area entirely.

He brought the matter to the council chambers at last Wednesdays council meeting and urged councillors to take immediate action to enhance the south end of the iconic street.

His presentation to councillors was met with applause from other residents in the chamber.

There is no reason why this area couldnt have been grassed, Mr Pola said. It is uninviting and doesnt add to the appeal of the residential heritage precinct and fails to meet the greenery and beautification aspirations of the city.

Mr Pola said the Melbourne City Council was already leading the way in beautifying Melbournes CBD through methods including grassing traffic islands.

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Ugly traffic islands prompt call for action

Bay of Islands SmartBay buoy to help boaters of all sorts

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The SmartBay buoy being launched in the outer Bay of Islands in early September.

Those who head out on the waters of the outer Bay of Islands can do so in a little smarter fashion these days.

Earlier this month, following consultations ACAP Humber Arm held with local user groups in 2011, the Marine Institute expanded its SmartBay project to the Bay of Islands.

The SmartBay project involves setting up specialized buoys in strategic locations to help improve the safety and knowledge of local users. The SmartBay buoys provide a wide range of data concerning conditions at the site, such as air and water temperatures, barometric pressure, wind speed and direction, wave height and other sea state information.

The buoys are also equipped with Aids to Navigation Information Systems, allowing direct transmittal of the buoys data to nearby vessels via the Internet.

The Bay of Islands buoy began providing data after it was launched just west of Woods Island in the outer Bay of Islands Sept. 10. Since the first SmartBay buoy launched inPlacentia Bay in 2006, similar buoys have been set up near the mouth of Channel-Port aux Basques, as well as in the Bay of Exploits near New World Island and near Cape Spear just outside of St. Johns Harbour in the past year. The buoys will be taken up for the winter when ice conditions warrant it.

Brian Brewer of Corner Brook is an avid sailor. He has yet to have a chance to put the navigational help offered by the buoy in the Bay of Islands to practical use, but will be checking it out next summer. Thats when he plans to sail his late father Gordon Brewers sailboat from Baddeck, N.S. across the Gulf of St. Lawrence to the marina in the Humber Arm.

Sailing anything, just knowing that buoy is there would be a benefit to anybody planning any sort of recreational boating in the outer bay, said Brewer. Its nice to know what conditions are there and how to plan for a trip.

The sea conditions inside the sheltered bay, noted Brewer, is often drastically different from what its like in the outer Bay of Islands.

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Bay of Islands SmartBay buoy to help boaters of all sorts

Smart buoys to improve safety, knowledge in Bay of Islands

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Those who head out on the waters of the outer Bay of Islands can do so in a little smarter fashion these days.

The SmartBay buoy being launched in the outer Bay of Islands in early September. Submitted photo

Earlier this month, following consultations ACAP Humber Arm held with local user groups in 2011, the Marine Institute expanded its SmartBay project to the Bay of Islands.

The SmartBay project involves setting up specialized buoys in strategic locations to help improve the safety and knowledge of local users. The SmartBay buoys provide a wide range of data concerning conditions at the site, such as air and water temperatures, barometric pressure, wind speed and direction, wave height and other sea state information.

The buoys are also equipped with Aids to Navigation Information Systems, allowing direct transmittal of the buoys data to nearby vessels via the Internet.

The Bay of Islands buoy began providing data after it was launched just west of Woods Island in the outer Bay of Islands Sept. 10. Since the first SmartBay buoy launched in Placentia Bay in 2006, similar buoys have been set up near the mouth of Channel-Port aux Basques, as we all as in the Bay of Exploits near New World Island and near Cape Spear just outside of St. Johns Harbour in the past year.

Brian Brewer of Corner Brook is an avid sailor. He has yet to have a chance to put the navigational help offered by the buoy in the Bay of Islands to practical use, but will be checking it out next summer. Thats when he plans to sail his late father Gordon Brewers sailboat from Baddeck, N.S., across the Gulf of St. Lawrence to the marina in the Humber Arm.

Sailing anything, just knowing that buoy is there would be a benefit to anybody planning any sort of recreational boating in the outer bay, said Brewer. Its nice to know what conditions are there and how to plan for a trip.

The sea conditions inside the sheltered bay, noted Brewer, is often drastically different from what its like in the outer Bay of Islands.

It is likely, said Brewer, that boaters will need a signal booster to access the Internet and the buoy information while on the water, where the signal is relatively weak.

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Smart buoys to improve safety, knowledge in Bay of Islands

Synthetic sperm protein raises the chance for successful in vitro fertilization

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30-Sep-2014

Contact: Cody Mooneyhan cmooneyhan@faseb.org 301-634-7104 Federation of American Societies for Experimental Biology @fasebopa

Having trouble getting pregnanteven with IVF? Here's some hope: A new research report published in October 2014 issue of The FASEB Journal, explains how scientists developed a synthetic version of a sperm-originated protein known as PAWP, which induced embryo development in human and mouse eggs similar to the natural triggering of embryo development by the sperm cell during fertilization.

"We believe that the results of this study represent a major paradigm shift in our understanding of human fertilization by providing a precise answer to a fundamental unresolved scientific question in developmental biology," said Mahmoud Aarabi, M.D., Ph.D., a researcher involved in the work from the Department of Human Genetics at Montreal Children's Hospital Research Institute in Montreal, Canada. "Based on our findings, we envision that physicians will be able to improve their diagnosis and treatment of infertility, a problem that affects 10-15 percent of couples worldwide, and scientists will be able to finally resolve the signalling pathway leading to initiation of embryonic development in mammals."

To make their advance, Aarabi and colleagues injected transcripts coding for PAWP protein into human eggs, and the immediate fertilization events, including release of calcium inside the eggs, were investigated carefully. (The human eggs used in this study were donated by infertile women and consisted of immature eggs that were further matured in the laboratory and thus were not suitable for IVF.) The injected eggs were fixed before cell division. A similar protocol was used in mice where the PAWP protein was injected into the eggs. The scientists found that when PAWP inhibitors were injected with the sperm cell into the eggs, a procedure known as ICSI in human infertility therapy, they blocked the sperm-induced fertilization. This is the first time that any sperm protein is shown to be susceptible to such an important inhibition effect.

"Reducing the number of IVF cycles for couple would save them money and disappointment," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Equally important, this research helps us better understand the events that occur when an egg is first fertilized as well as what we can do to influence those events."

###

Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is the world's most cited biology journal according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.

FASEB is composed of 27 societies with more than 120,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

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Medical College of Wisconsin awarded $2.5 million grant

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The Medical College of Wisconsin center that read a young boy's genetic script and diagnosed his mysterious disease, ushering in a new era of medicine, has won a $2.5 million grant to analyze the genes of patients with undiagnosed diseases.

Under the four-year grant from the National Institutes of Health, the college's Human and Molecular Genetics Center will collaborate with Illumina Inc. to sequence the genomes of 1,650 patients and their families a project that could answer a crucial question hanging over genetic medicine.

The award, the Medical College's first major sequencing grant after several unsuccessful attempts, will examine whether it makes more sense to search for diagnoses by scanning a major part of the genome, called the exome, or to expand the search to the full genome.

"That's a question that's on a lot of people's minds right now," said Anastasia Wise, program director overseeing the NIH grant the Medical College was awarded.

When Nic Volker, then 4 years old, had his genes sequenced in 2009, the Medical College and Children's Hospital of Wisconsin focused on a little more than 1% of the genome, the exome, which contains the recipes for making proteins. Since many diseases are caused by the failure to make proteins correctly, scientists thought exome sequencing was the most efficient way to diagnose patients.

However, since the breakthrough that pinned down the cause of Volker's intestinal illness and saved his life, the cost of sequencing the full genome, all 3.2 billion chemical bases, has dropped considerably. The chemical bases, adenine, guanine, thymine and cytosine, each one reduced to a letter (A, G, T and C), stretch out like 3.2 billion rungs on a ladder to form our genetic makeup everything from the color of our eyes and hair to our risks of different diseases.

Before Volker's sequence was read, scientists at the Medical College estimated that reading the genome could cost up to $2 million; as it turned out targeting only the exome reduced the cost to about $75,000.

Today, sequencing centers read a genome for about $2,000 to $3,000 and an exome for $500 to $1,000, Wise said.

At the Medical College, three of the nine patients diagnosed using genome sequencing could not have been diagnosed with the exome method, according Howard Jacob, director of the human and molecular genetics center.

The new grant "will directly test if whole genome sequencing makes more diagnoses than exome sequencing," Jacob said. "We're hypothesizing a 25% greater diagnostic rate with genome than with exome sequencing."

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Medical College of Wisconsin awarded $2.5 million grant

Larry Brown PhD interview with John McDonough, DrPH, MPA, – Video

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Larry Brown PhD interview with John McDonough, DrPH, MPA,
Reform Landscape of Health Care Delivery Conference, part of launch of MS Program in Health Care Delivery Leadership at Icahn School of Medicine at Mount Sinai Professor Larry Brown, PhD interviews...

By: Icahn School of Medicine

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Larry Brown PhD interview with John McDonough, DrPH, MPA, - Video

Standard & Poor’s U.S. Consumer, Retail, And Health Care Weekly Review (Sept. 29) – Video

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Standard Poor #39;s U.S. Consumer, Retail, And Health Care Weekly Review (Sept. 29)
In this segment of Standard Poor #39;s U.S. Consumer, Retail, and Health Care Weekly Review, Standard Poor #39;s Director Rick Joy highlights sector trends and the actions we recently took on Auxilium...

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Standard & Poor's U.S. Consumer, Retail, And Health Care Weekly Review (Sept. 29) - Video

Nova Scotia presses on with health-care bill as unions rally in protest

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Union protesters blocked traffic outside the Nova Scotia legislature Tuesday morning as the government pushes through legislation that changes the bargaining structure in the health-care system.

At one point a car carrying Premier Stephen McNeil was caught up in the protest.

A man who was part of the demonstration was handcuffed by police and put in the back of a police van.

The bill introduced by the provinces Liberal government would merge bargaining units. The government wants to cut the number of units to four from 50 by April 1.

Public-sector unions say the bill violates labour rights, but McNeil argues the legislation would protect patients and workers while ensuring health care is sustainable.

The government has put the bill on a fast-track. By using its majority in the house, the government can get the legislation approved and into committee by Wednesday.

In Question Period, Progressive Conservative Leader Jamie Baillie asked why the government combined the labour provisions of the bill with those that would cut the number of health authorities to two from 10. The Tories would prefer two bills to avoid disruption in the health-care system, he said.

About 500 union members protested outside the legislature on Monday when the bill was introduced, but the demonstration on Tuesday was much smaller.

On Monday, protester Lisa Gentile said the bill is an attack on unions.

As I see it they are trying to break the unions and they are going to start with health care and work their way through, said Gentile, a daycare worker from Glace Bay.

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Nova Scotia presses on with health-care bill as unions rally in protest

Health Authorities Act concerns union representing health care workers

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Published on September 29, 2014

The new Health Authorities Act was met with hostility even before its introduction in the Nova Scotia Legislature Monday evening.

A representative from the National Union of Public and General Employees, of which the Nova Scotia Government and General Employees Union is a component and is one of four unions representing health-care workers in the province, is calling the bill the most offensive piece of legislation relating to health care restructuring and unions that they have seen.

Larry Brown, an elected officer of the national union, was in Halifax for a briefing from the government about the legislation.

The legislation is deliberately presenting a falsehood to the people of Nova Scotia. It talks about a process of mediation as if somehow that was a real process. But in the legislation, its a charade. There is no possible way that mediation as described in the bill can work, he said.

In a media release, the government states that the act simplifies the labour landscape in health care, and promises mobility for health-care workers as well as a reduction of the number of rounds of bargaining from 50 to four.

All existing health-care unions will be kept, the release says, but mandates that workers who do the same types of jobs would be represented by the same union.

The provincial health authority and the IWK would bargain with unions under the act, and a mediator would work with unions and employers to determine which union will represent each of the four bargaining units, and other issues such as respecting seniority, the release says.

The act is not expected to impact wages, pensions, and health care benefits.

Right now, the health-care system spends between 1,000 and 2,000 hours each year on labour negotiations. We need our system to spend that time focusing on patients," said Glavine. "We need a labour structure that supports our provincial approach. Mediation will ensure that unions, and their members, continue to have a voice in what that structure looks like."

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11 NM colleges share in $15M health care grant

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A consortium of 11 two-year colleges led by Santa Fe Community College has been awarded $15 million in federal grants to offer new and additional training statewide for health care fields.

As the leader of the group, SFCC is getting about $5.6 million, some of which will be used for coordinating the effort among the various schools, said Randy Grissom, the colleges president.

The grants will go toward training and improving health care career pathways for college students, Grissom said. Those pathways will have multiple entry and exit possibilities, so that students will be able to move from one jurisdiction to another and remain in an educational program. The grants were announced Sunday by Vice President Joe Biden, Secretary of Labor Thomas Perez and Education Secretary Arne Duncan. Perez said his department has invested nearly $23 million in New Mexico over the last four years, part of a long-term commitment to ensure that workers have access to training for the specific skills employers need to stay competitive in the global economy.

The other schools in the consortium and the amounts of the individual grants are Central New Mexico Community College ($1,983,778), San Juan College ($1,366,921), Eastern New Mexico University Roswell ($1,145,444), Eastern New Mexico University Ruidoso ($576,767), New Mexico State University Alamogordo ($807,012), the University of New Mexico -Taos ($688,983), UNM -Valencia County ($788,029), UNM Los Alamos ($579,961), UNM Gallup ($866,967) and Mesalands Community College ($553,623).

SFCC took the lead in applying for the Labor Department grants, but all of the schools as well as other agencies were involved, Grissom said. He mentioned private sector groups and the Department of Workforce Solutions. An aide, Janet Wise, said the congressional delegation was also extremely helpful.

By 2030, New Mexico is expected to have the fourth-highest rate of residents 65 and older, Grissom said. The need for nurses, community health care workers, dental workers, home health aides and paramedics will be enormous, with a focus on creating access to health care in underserved and rural areas, workers who will interface with and advocate for the patient.

But the key to the story, he said, is how the 11 colleges got together and worked hard to come up with ways to serve New Mexico.

The New Mexico grants are part of $450 million in 71 grants awarded in all 50 states, Puerto Rico and the District of Columbia.

By 2020, six of every 10 jobs will require a credential beyond a high school degree, Biden said.

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11 NM colleges share in $15M health care grant

Health-care tech firm CoverMyMeds offered tax credits

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The Bottom Line Other Business Features Local Stories from ThisWeek More Articles By Mark Williams The Columbus Dispatch Tuesday September 30, 2014 3:13 AM

A Columbus health-care technology company has been offered state incentives to support growth plans that include adding 116 jobs in coming years.

CoverMyMeds plans to move from the Arena District to larger quarters in Downtowns Scioto Mile development and invest $1.2 million in the new space and equipment.

The Ohio Tax Credit Authority approved incentives worth an estimated $482,288 yesterday at its monthly meeting.

The company has 57 workers who together earn $2.3 million a year. The additional jobs would mean $7.4 million more in annual payroll.

Doctors, pharmacists and their staffs use CoverMyMeds software to work with health-insurance companies to obtain drug approval for patients.

Our software network that streamlines a vital process for physicians, pharmacies and health plans has led to rapid growth at CoverMyMeds, prompting the need for more space for specialized professionals, Alan Scantland, the companys CEO, said in a statement.

The company also plans to invest $2 million on a training program for software engineers.

Also receiving approval for state tax incentives was Columbus Steel Castings for its previously announced expansion on the South Side.

The company plans to add 550 jobs based on anticipated growth in demand for steel parts needed to make rail cars and because of growing sales of repair parts. The expansion will roughly double the companys workforce.

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Health-care tech firm CoverMyMeds offered tax credits

Pitt Researchers Search for Genetic Roots of Cleft Lip, Palate with Help from NIH Grant

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Pittsburgh, Pennsylvania (PRWEB) September 30, 2014

Researchers at the University of Pittsburgh School of Dental Medicine have been awarded a $11.8 million, five-year grant from the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health, to continue their exploration of the genetic roots of cleft lip and cleft palate and to expand the effort to include populations in Colombia, Nigeria, the Philippines and Pennsylvania.

Orofacial clefts (OFCs), which are small gaps in the lip or palate that can form when a babys mouth doesnt develop properly during pregnancy, occurs in 1 out of 700 live births worldwide, said Mary L. Marazita, Ph.D., professor and vice chair, Department of Oral Biology, and director of the Center for Craniofacial and Dental Genetics (CCDG).

Orofacial clefts present a significant public health challenge as these patients typically require surgical, nutritional, dental, speech and behavioral treatments for years, Dr. Marazita said. We hope to build on the progress weve made in our previous studies by identifying genetic susceptibility not only for the overt defects, but also for more subtle features such as changes in facial structure that we have found in relatives of participants with OFCs.

Dr. Marazita and Seth M. Weinberg, Ph.D., assistant professor of oral biology, and director of the CCDG Imaging and Morphometrics Lab, lead the coordinating center for the project, which includes researchers from the University of Iowa, the Newborn Screening Foundation in the Philippines, the Lancaster Cleft Palate Clinic, Nigerias University of Lagos, Colombias Foundation Clinica Noel, and KU Leuven University in Belgium.

For the works next phase, the team will recruit for genetic studies about 6,100 individuals from more than 1,500 families with a history of cleft lip with or without cleft palate, or cleft palate alone, from a low-risk population in Nigeria; high-risk populations in the Philippines and Colombia; and mid-risk populations in Pittsburgh and Lancaster, Pa., as well as 2,000 unrelated individuals with no history of OFC.

Recent studies indicate different genes seem to be involved in different ethnic groups, so we must broaden our perspective to understand the factors that lead to clefts, Dr. Weinberg said. We have limited information about the development of cleft palate alone, for example. This research effort will greatly add to our knowledge.

The team also will assess participants for subclinical manifestations of genetic predisposition for OFCs with high-resolution ultrasound scanning of mouth muscles, lip print patterns, 3-D imaging of facial surfaces and more. Their previously published studies have shown that relatives of OFC patients are more likely to have subtle defects in the orbicularis oris muscle around the mouth, and facial differences such as mid-face retrusion and wider faces. OFC patients also report a family history of cancer more often than unaffected individuals, noted Dr. Marazita.

Minor dental abnormalities, facial shape differences, altered speech patterns and other less obvious changes in the mouth could all be part of a spectrum of defects that have the same genetic causes as cleft lip and palate, she said. If we can unravel those relationships and identify the biological pathways that cause them, we will gain insights that may lead to better treatments and better long-term outcomes for affected individuals.

# # # About the University of Pittsburgh School of Dental Medicine

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Pitt Researchers Search for Genetic Roots of Cleft Lip, Palate with Help from NIH Grant

Genetic test would help 'cut bowel cancer spread'

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PUBLIC RELEASE DATE:

30-Sep-2014

Contact: Chris Jones jonesc83@cardiff.ac.uk Cardiff University @cardiffuni

Screening families of patients with bowel cancer for a genetic condition would cut their risk of developing bowel, womb, and ovarian cancers, new research has found.

In a major study, Dr Ian Frayling from Cardiff University's School of Medicine and researchers from the University of Exeter's Medical School assessed the effectiveness of introducing a UK-wide screening programme for a genetic condition known as Lynch Syndrome.

Lynch syndrome is a caused by changes in genes which check the spelling in DNA. The condition increases the risk of people developing cancer, particularly bowel cancer and cancers of the womb and ovaries later in life. Without testing cancers, it is not obvious that they are caused by Lynch syndrome, and so it is often not diagnosed.

It is responsible for around one in 12 cases of people aged under 50 and around a third of people with the disease develop bowel cancer by the time they are 70, if no action is taken.

"If Lynch Syndrome is identified as the cause of bowel cancer, patients can be offered risk-reducing measures such as more intensive post-operative colonoscopy surveillance to spot recurrences and new cancers early," according to Cardiff University's Dr Ian Frayling, the clinical adviser to the study.

"As close relatives have a 50 per cent chance of sharing the gene, screening would provide a valuable opportunity to detect the condition in children, siblings, parents and more distant relatives.

"It would mean measures could be taken to reduce the risk of cancers developing," he added.

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Genetic test would help 'cut bowel cancer spread'

Liver gene therapy corrects heart symptoms in model of rare enzyme disorder

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PUBLIC RELEASE DATE:

29-Sep-2014

Contact: Karen Kreeger karen.kreeger@uphs.upenn.edu 215-349-5658 University of Pennsylvania School of Medicine @PennMedNews

PHILADELPHIA In the second of two papers outlining new gene-therapy approaches to treat a rare disease called MPS I, researchers from Perelman School of Medicine at the University of Pennsylvania examined systemic delivery of a vector to replace the enzyme IDUA, which is deficient in patients with this disorder. The second paper, which is published online in the Proceedings of the National Academy of Sciences this week, describes how an injection of a vector expressing the IDUA enzyme to the liver can prevent most of the systemic manifestations of the disease, including those found in the heart.

The first paper, published in Molecular Therapy, describes the use of an adeno-associated viral (AAV) vector to introduce normal IDUA to glial and neuronal cells in the brain and spinal cord in a feline model. The aim of that study was to directly treat the central nervous system manifestations of MPS while the more recent study aims to treat all other manifestations of the disease outside of the nervous system.

This family of diseases comprises about 50 rare inherited disorders marked by defects in the lysosomes, compartments within cells filled with enzymes to digest large molecules. If one of these enzymes is mutated, molecules that would normally be degraded by the lysosome accumulate within the cell and their fragments are not recycled. Many of the MPS disorders can share symptoms, such as speech and hearing problems, hernias, and heart problems. Patient groups estimate that in the United States 1 in 25,000 births will result in some form of MPS. Life expectancy varies significantly for people with MPS I.

The two main treatments for MPS I are bone marrow transplantation and intravenous enzyme replacement therapy (ERT), but these are only marginally effective or clinically impractical, and have significant drawbacks for patient safety and quality of life and do not effectively address some of the most critical clinical symptoms, such as life-threatening cardiac valve impairments.

"Both of these papers are the first proof-of-principle demonstrations for the efficacy and practicality for gene therapies to be translated into the clinic for lysosomal storage diseases," says lead author James M. Wilson, MD, PhD, professor of Pathology and Laboratory Medicine and director of the Penn Gene Therapy Program. "This approach may likely turn out to be better than ERT and compete with or replace ERT. We are especially excited about the use of this approach in treating the many MPS I patients who do not have access to ERT due to cost or inadequate health delivery systems to support repeated protein infusions, such as in China, Eastern Europe, India, and parts of South America."

Patients with mucopolysaccharidosis type I (MPS I), accumulate compounds called glycosaminoglycans in tissues, with resulting diverse clinical symptoms, including neurological, eye, skeletal, and cardiac disease.

Using a naturally occurring feline model of MPS I, the team tested liver-directed gene therapy via a single intravenous infusion as a means of establishing long-term systemic IDUA presence throughout the body.

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Liver gene therapy corrects heart symptoms in model of rare enzyme disorder

Gene Therapy Targeting Liver Corrects Cardiovascular Symptoms in Animal Model of Rare Enzyme Deficiency Disease

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PHILADELPHIA In the second of two papers outlining new gene-therapy approaches to treat a rare disease called MPS I, researchers from Perelman School of Medicine at the University of Pennsylvania examined systemic delivery of a vector to replace the enzyme IDUA, which is deficient in patients with this disorder. The second paper, which is published online in the Proceedings of the National Academy of Sciences this week, describes how an injection of a vector expressing the IDUA enzyme to the liver can prevent most of the systemic manifestations of the disease, including those found in the heart.

The first paper, published in Molecular Therapy, describes the use of an adeno-associated viral (AAV) vector to introduce normal IDUA to glial and neuronal cells in the brain and spinal cord in a feline model. The aim of that study was to directly treat the central nervous system manifestations of MPS while the more recent study aims to treat all other manifestations of the disease outside of the nervous system.

This family of diseases comprises about 50 rare inherited disorders marked by defects in the lysosomes, compartments within cells filled with enzymes to digest large molecules. If one of these enzymes is mutated, molecules that would normally be degraded by the lysosome accumulate within the cell and their fragments are not recycled. Many of the MPS disorders can share symptoms, such as speech and hearing problems, hernias, and heart problems. Patient groups estimate that in the United States 1 in 25,000 births will result in some form of MPS. Life expectancy varies significantly for people with MPS I.

The two main treatments for MPS I are bone marrow transplantation and intravenous enzyme replacement therapy (ERT), but these are only marginally effective or clinically impractical, and have significant drawbacks for patient safety and quality of life and do not effectively address some of the most critical clinical symptoms, such as life-threatening cardiac valve impairments.

Both of these papers are the first proof-of-principle demonstrations for the efficacy and practicality for gene therapies to be translated into the clinic for lysosomal storage diseases, says lead author James M. Wilson, MD, PhD, professor of Pathology and Laboratory Medicine and director of the Penn Gene Therapy Program. This approach may likely turn out to be better than ERT and compete with or replace ERT. We are especially excited about the use of this approach in treating the many MPS I patients who do not have access to ERT due to cost or inadequate health delivery systems to support repeated protein infusions, such as in China, Eastern Europe, India, and parts of South America.

Patients with mucopolysaccharidosis type I (MPS I), accumulate compounds called glycosaminoglycans in tissues, with resulting diverse clinical symptoms, including neurological, eye, skeletal, and cardiac disease.

Using a naturally occurring feline model of MPS I, the team tested liver-directed gene therapy via a single intravenous infusion as a means of establishing long-term systemic IDUA presence throughout the body.

The team treated four MPS I cats at three to five months of age with an AAV serotype 8 vector expressing feline IDUA. We observed sustained serum enzyme activity for six months at approximately 30 percent of normal levels in one animal and in excess of normal levels in the other three animals, says Wilson.

Remarkably, treated animals not only demonstrated reductions in glycosaminoglycans storage in most tissues, but most also exhibited complete resolution of aortic valve lesions, an effect which has not been previously observed in this animal model or in MPS I patients treated with current therapies.

Critical to the evaluation of these novel therapies is the feline model of MPS I, which was provided through coauthor Mark E. Haskins, School of Veterinary Medicine at Penn. Haskins and his colleagues maintain a variety of canine and feline models of human genetic diseases that have been instrumental in establishing proof of concept for a number of novel therapeutics, including the current enzyme replacement therapy.

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Gene Therapy Targeting Liver Corrects Cardiovascular Symptoms in Animal Model of Rare Enzyme Deficiency Disease