Research News

Welcome to the National Information and Advice Centre for Metabolic Diseases Research News Sheet - Vol 1 No 10.

The contents of this news sheet has been gathered from around the globe during our research to update our information on metabolic diseases. The contents are general and not specific to our cause.

Climb Book Launched – Inherited Metabolic Diseases – A Guide to 100 Conditions

Climb has launched it’s first book of information on 100 conditions. The book is titled Inherited Metabolic Diseases – A Guide to 100 Conditions and contains family-friendly information on a range of disorders from each of our ten groups. The book is available to buy from Amazon.com and will also be available to buy from Climb HQ shortly. Please contact Climb if you wish to order a copy.

Synopsis
Inherited Metabolic Diseases are common enough for health, social service and education professionals to encounter them periodically, but rare enough for them to be poorly understood. They severely affect up to 1 in 10,000 people, and lead to a wide range of special needs in care and education. This guide provides specialist information on metabolic diseases for the non-specialist. In a concise, accessible and family-friendly format, each entry lists the names by which a condition is known, and explains the genetic causes of the disease, the physical effects, the patient's symptoms, and available treatments. Key diseases from all ten major groups of metabolic disorders are described, and all entries have been reviewed by Specialist Advisers. The work has been coordinated by the charity Climb, Children Living with Inherited Metabolic Diseases. This uniquely comprehensive source of information is a vital reference for hospital doctors including paediatricians, general practitioners, nurses and other health professionals, social service and education staff and managers, and the families and carers of children with the conditions.

All babies in England are to be screened for an inherited metabolic disease called Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD), within two weeks of birth, announced Health Minister, Ivan Lewis.

The check will be carried out as part of the standard "heel-prick" test for babies that screens for other diseases such as sickle cell disorders and congenital hypothyroidism.

MCADD is a rare inherited metabolic disease that reduces the ability to maintain a normal blood sugar during episodes of metabolic stress.

MCADD affects between one in 10,000 and one in 20,000 babies born in the UK and screening should identify around 28 cases a year in England.

If the disease is not identified at an early stage, around a quarter of affected children will die from the condition, with one third of survivors sustaining significant neurological damage.

Once babies are identified and given simple treatment, the risk of acute, life-threatening episodes needing emergency and intensive care and of death is substantially reduced.

"I am delighted that all newborn babies will be screened for MCADD. Not only will the introduction of this screening programme save lives it will improve the quality of life for those children affected by this condition"

"This is a very important screening programme and I fully support its implementation. Evidence shows that screening newborn babies for this condition will not only save lives but it can significantly improve their quality of life. Simple treatment through dietary management will substantially reduce the risk of death and the risk of acute, serious illness."

Ministers asked the UK National Screening Committee (NSC) to set up a pilot study to provide essential evidence in an NHS setting of the clinical and cost effectiveness of screening for this condition and the feasibility of implementation. The final report will be available in 2008 but sufficient evidence and analysis was available for the NSC to make its recommendation that newborn screening of all babies would be clinically and cost effective in the UK.

There will be a planned roll out of the screening programme over the next two years.

Public enquiries to 020 7210 4850.

Treatment Hope for Rett Syndrome

The symptoms of a severe autism spectrum disorder affecting at least 10,000 children in the UK could be reversed following findings from the University of Edinburgh.

Rett Syndrome, which can leave children wheelchair bound, unable to speak and suffering from breathing difficulties, has until now been considered an untreatable neurological disorder.

But experts at the University of Edinburgh have now been able to make symptoms disappear in mice by activating a specific gene.

Research focused on the behaviour of the MECP2 gene that causes the syndrome to develop. They found that when this gene was activated in mice, which had previously been born with it switched off, symptoms such as breathing and mobility difficulties ceased. Over a four week period, the mice often became undistinguishable from healthy counterparts.

The findings give impetus to ways of treating Rett Syndrome, which mainly affects girls. Further research may also show that the results could apply to other autism spectrum disorders.

Prof Adrian Bird, Director of the Wellcome Trust Centre for Cell Biology at the University of Edinburgh, led the research and first discovered the MECP2 gene in 1990. He said:

“The results we came across were entirely unexpected. Until now it had been thought that Rett Syndrome is irrevocable, but our findings show that the damage to nerve cell function is, in fact, reversible. This gives a major boost to the search for treatments or a potential cure.”

The research, which is published online by the journal Science, was funded by the Wellcome Trust, Rett Syndrome Association UK (with support from Jeans-for-Genes) and the US-based Rett Syndrome Research Foundation.

Although Rett Syndrome is present at birth, it becomes more evident during the second year. It is believed to be the second most common cause of severe and profound learning disability in girls.

Potential treatment, following on from the research, could range from overriding the mutated version of MECP2 with the activation of a healthy version of the gene. Alternatively, therapy could focus on drug treatment to inhibit the action of proteins expressed as a result of a MECP2 mutation.

“The Rett Syndrome Association UK is extremely delighted to hear about the results of Professor Bird's research.

“This is a very significant step on the road for future therapeutic approaches to Rett syndrome and, whilst the work in this area is still at an early stage, it will give hope to those families affected by Rett syndrome.

“It is particularly pleasing for us that we have been able to help fund this research that could have such a positive benefit for people with Rett Syndrome, their families and carers.”

Orphan Europe and Rare Disease Therapeutics partner to provide Cystadane® to Homocystinuria patients in USA and Canada

Orphan Europe has signed a licensing agreement with Rare Disease Therapeutics who will market Cystadane, indicated for homocystinuria, in USA and Canada.

Homocystinuria is a rare disease of genetic origin, affecting the methionine metabolism. This severe disease results in elevated homocysteine levels (toxic at these concentrations) throughout the body.

Homocystinuria causes a variety of sometimes severe symptoms involving mainly ocular, nervous and vascular systems, as well as the bones. These symptoms can include mental retardation, seizures, psychiatric disturbances, osteoporosis, scoliosis, marfanoid features and thromboembolic complications. The latter may lead to stroke, seizures, permanent neurologic sequellae and even death. If left untreated, 25% of homocystinuria patients die before the age of 30.

Cystadane® lowers the toxic homocysteine levels by activating an alternative metabolic pathway for the metabolization of homocysteine. Patients receiving a treatment effectively lowering homocysteine levels have a significantly reduced risk of potentially life threatening thromboembolic events.* Cystadane® has marketing approval in the US, Canada, Europe, Australia and Israel and is marketed directly by Orphan Europe in the rest of the world.

Rare Disease Therapeutics, Inc. (RDT) is a well established company founded in 1991 and located in Nashville, Tennessee, USA. RDT has a solid track record with multiple licensing agreements, a comprehensive global patient advocacy network, and significant success in drug development and approval. RDT works closely with the FDA Office of Orphan Product Development, National Organization for Rare Disorders, the National Institutes of Health, large international pharmaceutical companies, and patient advocacy groups to identify the unmet needs of patients with rare diseases and potential products to meet these needs.

“We are very pleased to be able to make Cystadane® available for homocystinuria patients in US and Canada” said Mr. Milton H. Ellis, President of RDT. “This acquisition reinforces our product portfolio of efficient treatment for rare disease patients.”

“In RDT we found our perfect partner for the important North-American market”, says Mr. William Gunnarsson, CEO of Orphan Europe.” They have the knowledge and commitment necessary to provide care for rare disease patients”.

* Yap S, Boers GH, Wilcken B, Wilcken DE, Brenton DP, Lee PJ,Walter JH, Howard PM, Naughten ER, Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study, Arterioscler Thromb Vasc Biol. (2001 Dec) 21(12):2080-5.

Stem cell study, including the first successful use of human embryonic stem cells in degenerative disease, lays ground work for clinical bridge.

Human embryonic stem cells (hESCs) hold great promise for benefiting degenerative diseases, and do so by invoking multiple mechanisms. Such cells can be grown in a manner compatible with clinical use (i.e., without animal feeder layers) and even without the need for immunosuppression. These were a few of a number of conclusions arrived at by an international collaboration led by Evan Y. Snyder, M.D., Ph.D., and spearheaded by a member of his lab, Jean-Pyo Lee, Ph.D., of the Burnham Institute for Medical Research (“Burnham”). The study, to be published in Nature Medicine, will be made available by advanced publication at the journal’s website on March 11, 2007.

To determine whether stem cell biology might play a role in benefiting degenerative diseases, the investigators first chose to approach, as proof-of-concept, a mouse model of a representative lethal neurodegenerative disease. Next, they used mouse neural stem cells (NSCs), a type of “adult” stem cell, to establish the parameters of what might or might not be achievable in this disease. Then, having demonstrated success with mouse cells, they extended those insights to stem cells of human origin, both human neural stem cells and human embryonic stem cells, and, in fact, had the opportunity, for the first time, to compare those two types of controversial stem cells head-to-head in the same model. The results, described in more detail below, in fact prove to be the first successful use of human embryonic stem cells in treating a degenerative disease, significantly preserving function and extending life.

The mouse model chosen falls in a class of genetic diseases that afflicts 1 in 5000 patients, typically children (called lysosomal storage diseases, described in more detail below), but which is often used to model an array of adult neurodegenerative diseases such as Parkinson’s, ALS, Alzheimer’s – particularly those with a genetic component. The mouse used here has mutation in a gene that makes the housekeeping enzyme hexosaminidase (“hex”) deficient and, therefore, has Sandhoff Disease, a lethal genetic disease related to Tay-Sachs Disease. When stem cells were implanted – at simply one time point – into brains of newborn Sandhoff mice, the onset of symptoms was delayed, well-being and motor function was preserved, and lifespan was extended by >70%.

The researchers discovered that their implanted neural stem cells, which migrated and integrated extensively throughout the brain, did much more than replace brain tissue destroyed by the disease. Some of the transplanted cells replaced damaged nerve cells and transmitted nerve impulses, offering the first evidence that stem cell-derived nerve cells may integrate electrically and functionally into a diseased brain. The transplanted cells also boosted the brain’s supply of the enzyme Hex, which reduced the lipid accumulations in the treated animals. The experimental treatment also dampened the inflammation that typically occurs in the brains of most degenerative diseases, including Sandhoff, and likely contributes to disease progression.

“Our studies suggest that functional neuronal replacement can be complemented and, under some conditions, eclipsed by a range of other stem cell actions that nevertheless exert a number of critical stabilizing forces,” said Dr. Snyder, director of Stem Cells and Regeneration at Burnham. “In fact, our study offers the first evidence that stem cells employ multiple mechanisms – not just cell replacement — which collaborate to benefit disease. These findings also raise the possibility – somewhat counter-intuitively – that stem cells may inherently exert an anti-inflammatory influence in degenerative diseases,” said Snyder.

To demonstrate that a better understanding of the fundamental mechanisms of stem cell action may permit the development of rational combined synergistic therapies, the investigators then gave the mice a simple oral drug that permitted the amount of enzyme provided by the engrafted stem cells to work even more efficiently by presenting them with a smaller burden of material to metabolize. The lifespan of the mice doubled. (Neither treatment could work as effectively on its own. In fact, the effect was more than simply additive). This was a demonstration that stem cell efficacy could be enhanced even without the need for genetic engineering. (The drug, a glycosphingolipid biosynthesis inhibitor, is in a class of compounds called “substrate reduction therapy” drugs.) This part of the study not only represented the first “multidisciplinary” use of stem cells against a degenerative disease, but also highlighted the fact that, in the future, the most successful therapies – including those employing stem cells – will likely invoke the use of multiple strategies in concert. Indeed, the stem cell may be the “glue” that ultimately holds these therapies together in an effective manner by virtue of its fundamental biology.

The researchers then sought to extend their insights to the use of human stem cells – either stem cells turned into neural progenitors from human embryonic stem cells – or isolated directly from the nervous system (called “adult” stem cells to distinguish them from embryonic stem cells even though they are taken from developing brain tissue). Both types of human stem cells were actually somewhat more effective than the mouse neural stem cells. And, they were equally as good as each other – in the first head-to-head comparison ever done between embryonic and “adult” stem cells, although the embryonic stem cells were somewhat easier to “scale up” into large quantities. Both types of human stem cells invoked the same range of multiple, collaborative mechanisms. Neither type of human stem cell created tumors, deformation, a worsening of symptoms, or gave rise to inappropriate cells types. Neither cell type was rejected by the immune system. In fact, no immunosuppression was needed at all. Finally, the human embryonic stem cells were grown without mouse feeder layers and in a “defined” culture medium that is compatible with clinical use and demonstrating for the first time that such preparations are consistent with a therapeutic impact.

Sandhoff results from a genetic mutation that reduces the body’s supply of an enzyme, called hexosaminidase (“hex”), used by brain cells to metabolize excess fatty material called lipids. Onset is typically at six months in human infants. The accumulation of lipids in brain tissue destroys the brain cells instrumental in controlling and coordinating body movement and results in inexorable deterioration of the brain and spinal cord. Children suffering with Sandhoff rarely see their sixth birthday. Sandhoff mice are similarly affected. Tay-Sachs is predominant to Ashkenazi Jewish populations, while Sandhoff, a severe form of Tay-Sachs, is not limited to any ethnic group. Both diseases are marked with deficient Hex enzyme functioning and are among a known group of about 50 diseases rooted in the inability to metabolize lipids or other materials. While Sandhoff and Tay-Sachs are relatively rare, one person in 5,000 is affected by a disease that falls into a category of lysosomal storage diseases.

Currently there is no treatment for Sandhoff or Tay-Sachs. Given that the human stem cells used in this study – both human neural and embryonic stem cells – were safe and effective in so many mice, the researchers believe that their study may serve as a springboard for development into a clinical trial.

These diseases are part of a much more common group of diseases called “neurogenetic diseases”. These findings contribute fundamental basic knowledge about stem cell biology that will help inform medical scientists in their quest for understanding diseases such as Parkinson’s, Alzheimer’s, ALS, and a host of other neurological diseases.

“Dr. Snyder’s team has extended the promise of stem cell therapies to children with special-needs, including those with Sandhoff disease.” said Fia Richmond, founder of Children's Neurobiological Solutions Foundation and mother of a brain-injured child. “The CNS Foundation is proud to have contributed major funding for this research along with A-T Children's Project on behalf of the 14 million special-needs children in this country alone.”

This study is the culmination of a long-standing collaboration between Drs. Frances Platt and Mylvaganam Jeyakumar of the University of Oxford in Oxford, UK and the Drs. Evan Snyder and Jean-Pyo Lee of The Burnham Institute in LaJolla, California.

Amicus Therapeutics Presents Positive Results from Phase 1 Clinical Studies of Plicera™ for Gaucher Disease

Cranbury, NJ, March 21, 2007 – Amicus Therapeutics, a biopharmaceutical company developing small molecule, orally-administered pharmacological chaperones for the treatment of a range of human genetic diseases, announced today that it will present positive results from its recently completed Phase 1 clinical studies of Plicera™ (isofagomine tartrate, AT2101) for Gaucher disease at the American College of Medical Genetics (ACMG) Annual Meeting on March 21-25 in Nashville, TN. The Phase 1 results show that Plicera was well-tolerated and that oral administration resulted in a significant elevation of target enzyme levels in healthy volunteers. Based on these results, Amicus announced today the initiation of two Phase 2 clinical trials of Plicera for Gaucher disease.

Plicera is designed to selectively bind to and stabilize GCase, the enzyme deficient in Gaucher disease. This deficiency leads to lysosomal accumulation of glucocerebroside inside certain cells, which is believed to cause the various symptoms of Gaucher disease. Plicera facilitates proper trafficking of the enzyme to the lysosomes, the compartments in the cell where it is needed to break down glucocerebroside.

Phase 1 Plicera data being presented at ACMG

Two double-blind, placebo-controlled, dose escalation Phase 1 studies in healthy volunteers were completed. These studies were designed to evaluate the safety, tolerability and pharmacokinetics of Plicera. In the first study, 36 subjects received a single dose of one of five dose levels of Plicera. The second study was a multiple-dose study in which 18 subjects received one of three dose levels of Plicera once daily for 7 consecutive days. In both studies, Plicera was safe and well tolerated at all doses. There were no serious adverse events and no subjects withdrew or discontinued due to an adverse event. In the multiple-dose study, a dose-dependent increase in GCase levels was observed in white blood cells from healthy volunteers receiving Plicera.

Based on the Phase 1 results, Amicus has initiated two Phase 2 clinical trials of Plicera for Gaucher disease. One is a 4-week study designed to evaluate the safety and pharmacodynamic effects of Plicera in Type I Gaucher patients who will discontinue enzyme replacement therapy for the duration of the study. The second is a 6-month study designed to evaluate the safety of Plicera and its effect on parameters that are commonly abnormal in Gaucher disease. This study will be conducted in Type I Gaucher patients who have never received enzyme replacement therapy.

Gaucher disease, the most commonly diagnosed lysosomal storage disorder, is caused by inherited genetic mutations in the GBA gene, which result in deficient activity of the enzyme acid β-glucosidase, also known as glucocerebrosidase (GCase). Deficient GCase activity leads to lysosomal accumulation of glucocerebroside inside certain cells, which is believed to cause the various symptoms of Gaucher disease, including an enlarged liver and spleen, abnormally low levels of red blood cells and platelets and skeletal complications. In some cases there is significant impairment of the central nervous system. Gaucher disease affects an estimated 8,000 to 10,000 people worldwide. The U.S. Food and Drug Administration’s Office of Orphan Products Development has granted orphan drug designation for the active ingredient in Plicera in the United States.

About Amicus Therapeutics

Amicus Therapeutics is a biopharmaceutical company developing novel, oral therapeutics known as pharmacological chaperones for the treatment of a range of human genetic diseases. Pharmacological chaperone technology involves the use of small molecules that selectively bind to and stabilize proteins in cells, leading to improved protein folding and trafficking, and increased activity. Amicus is initially targeting lysosomal storage disorders, which are severe, chronic genetic diseases with unmet medical needs. Amicus is currently conducting Phase 2 clinical trials for its two lead compounds, Amigal™ for Fabry disease, and Plicera™ for Gaucher disease. The company is currently conducting Phase 1 trials with AT2220 for the treatment of Pompe disease.

NOVATO, Calif., May 2 /PRNewswire-FirstCall/ -- BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN) today announced that the first patient has initiated treatment in the Phase 2a clinical study of 6R-BH4 (sapropterin dihydrochloride) for the treatment of sickle cell disease (SCD). The company expects to announce data from this study in the first half of 2008.

"The sickle cell disease indication fits well strategically with our focus on rare, undertreated genetic diseases. SCD is an orphan disease with 70,000 to 100,000 patients in the United States, according to the CDC. It is well- diagnosed at birth, but there is only one approved drug treatment option currently available which is used by a minority of patients due to toxicity problems," said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin. "6R-BH4 is an essential enzyme cofactor that is involved in the production of nitric oxide, a molecule that has been shown to play a role in the regulation of endothelial function. Studies of SCD patients suggest that endothelial dysfunction may play a role in sickle cell disease, and studies in an animal model of SCD suggest the potential utility of 6R-BH4 in the treatment of the vascular problems found in this disease."

The Phase 2a multi-center, open-label study is designed to assess the safety and biologic activity of escalating doses of 6R-BH4 in patients with SCD. The study will be conducted at approximately six U.S. sites and will enroll approximately 40 subjects. Among other eligibility criteria, to participate in the study, SCD patients must be at least 15 years of age and not receiving hydroxyurea therapy. Study patients will initially receive a low, once daily oral administration of 6R-BH4 (2.5 mg/kg) and will gradually escalate every four weeks to a final dose of 20 mg/kg/day during a 16-week dose-escalation phase. Patients will be monitored for physiological and biochemical markers of endothelial function. After 16 weeks, patients who show improvement in physiological or biochemical markers of endothelial function and/or derive clinical benefit from 6R-BH4 will have the option to continue drug treatment for up to two years. During this long-term treatment period, patients will also be monitored for sickle cell crises and other vasoocclusive events which are the key problems facing SCD patients.

The primary objective of this study is to evaluate the safety of oral 6R- BH4 administered in escalating doses in patients with sickle cell disease. The secondary objective is to evaluate changes in physiological and biochemical markers of endothelial function which underlie some key aspects of SCD.

6R-BH4, commonly known as BH4 or tetrahydrobiopterin, is a naturally occurring enzyme cofactor that is required for numerous biochemical and physiologic processes, including the synthesis of nitric oxide (NO). NO has been shown to play a key protective role throughout the cardiovascular system and produces multiple positive effects, such as relaxing smooth muscle, reducing blood pressure, controlling inflammation and reducing platelet aggregation. Researchers have demonstrated that a deficiency of BH4 can disrupt NO synthesis, resulting in a loss of normal endothelial NO production. This loss of endothelial NO production, commonly referred to as endothelial dysfunction, has been associated with many cardiovascular diseases, including diabetic vascular disease, peripheral arterial disease, coronary arterial disease and pulmonary hypertension, and has been shown to be a strong predictor of cardiovascular adverse events in a number of clinical studies.

6R-BH4 is the same enzyme cofactor currently being evaluated in BioMarin's Kuvan(TM) (sapropterin dihydrochloride) for phenylketonuria (PKU). In March 2006, BioMarin and Merck Serono (a division of Merck KGaA, Darmstadt, Germany), BioMarin's corporate partner for the Kuvan and 6R-BH4 programs, announced positive results from the Phase 3 clinical study of Kuvan for PKU. All primary and secondary endpoints of the study were met. The type and incidence of adverse events was similar in the Kuvan and placebo groups. Kuvan was well tolerated and investigators reported that no serious adverse event occurred.

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio is comprised of two approved products and multiple clinical and preclinical product candidates. Approved products include Naglazyme(R) (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin, and Aldurazyme(R) (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation. Investigational product candidates include Kuvan(TM) (sapropterin dihydrochloride), a Phase 3 product candidate for the treatment of phenylketonuria (PKU), and 6R-BH4 for cardiovascular indications, which is currently in Phase 2 clinical development for the treatment of peripheral arterial disease. For additional information, please visit www.BMRN.com. Information on BioMarin's website is not incorporated by reference into this press release.

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including, without limitation, statements about: the timing of BioMarin's clinical trials of 6R-BH4 for sickle cell disease; the continued clinical development of 6R-BH4; expectation regarding regulatory filings for Kuvan; and actions by regulatory authorities, including actions related to 6R-BH4. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of 6R-BH4 for sickle cell disease; actions related to Kuvan; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities concerning each of the described product candidates; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's 2006 Annual Report on Form 10-K, as amended, and the factors contained in BioMarin's reports on Form 8-K. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.

CONTACT: Investors, Eugenia Shen, +1-415-506-6570, or
Media, Susan Berg, +1-415-506-6594, both of BioMarin Pharmaceutical Inc.

Web site: http://www.bmrn.com

VYVANSE™ (lisdexamfetamine dimesylate) Receives Final DEA Schedule Classification, Clearing Way for Launch of First Prodrug Stimulant for Treatment of ADHD

Basingstoke, U.K., Philadelphia, PA – May 3, 2007 – Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announced today that the U.S. Drug Enforcement Administration (DEA) has classified VYVANSE (lisdexamfetamine dimesylate, formerly known as NRP104), as a Schedule II controlled substance, following the earlier recommendation of the U.S. Food and Drug Administration (FDA).

The DEA schedule classification of VYVANSE represents the final step in the Federal

government’s administrative approval process before Shire begins commercialization of this novel ADHD treatment. The DEA has published this decision in the Federal Register today with an effective date of June 4, as required by law. The FDA approved the New Drug Application (NDA) for VYVANSE for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) on February 23, 2007. The product launch of VYVANSE remains on track for Q2 2007.

“The decision by the DEA was anticipated. All ADHD stimulant medications have historically been classified as Schedule II controlled substances,” said Matthew Emmens, Shire Chief Executive Officer. “VYVANSE is the first ADHD stimulant to have the results of abuse liability studies reflected in its product label. Shire plans to continue to build the body of evidence in support of a lower abuse potential profile.

VYVANSE is a prodrug stimulant that is therapeutically inactive until metabolized in the body.1 In clinical studies designed to measure duration of effect, VYVANSE provided consistent ADHD symptom control compared to placebo throughout the day, even at 6:00 pm.1

When VYVANSE was administered orally and intravenously in two human studies that evaluated abuse potential, VYVANSE produced subjective responses on a scale of “Drug Liking Effects” (DLE) that were less than d-amphetamine at equivalent doses.1 DLE is used in clinical studies to assess the abuse potential of a drug among known substance abusers.

“VYVANSE will provide physicians with a novel treatment option,” said Robert Findling, MD, study investigator and Director, Division of Adolescent and Child Psychiatry, University Hospitals Case Medical Center. “Clinical studies have shown that VYVANSE offers significant efficacy for up to 12 hours and significantly less abuse-related liking effects at equivalent oral doses of the active ingredient, d-amphetamine.”

On April 20, 2007, Shire announced that it completed its acquisition of New River

Pharmaceuticals Inc. (“New River”) pursuant to a short-form merger. The completion of the acquisition will allow Shire to drive the launch and future development of VYVANSE and

Additional information about VYVANSE and Full Prescribing Information are available at www.Vyvanse.com.

VYVANSE should not be taken by patients who have advanced arteriosclerosis; symptomatic cardiovascular disease; moderate to severe hypertension; hyperthyroidism; known hypersensitivity or idiosyncrasy to sympathomimetic amines; agitated states; glaucoma; a history of drug abuse; or during or within 14 days after treatment with monoamine oxidase inhibitors (MAOIs). Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems.

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses in ADHD. Physicians should take a careful patient history, including family history, and physical exam, to assess the presence of cardiac disease. Patients who report symptoms of cardiac disease such as exertional chest pain and unexplained syncope should be promptly evaluated. Use with caution in patients whose underlying medical condition might be affected by increases in blood pressure or heart rate. New psychosis, mania, aggression, growth suppression, and visual disturbances have been associated with the use of stimulants. Use with caution in patients with a history of psychosis, seizures or EEG abnormalities, bipolar disorder, or depression. Growth monitoring is advised

Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic uses or distribution to others and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. The most common adverse events reported in clinical studies of VYVANSE were loss of appetite, insomnia, abdominal pain, and irritability.

"Safe Harbour” Statement under the Private Securities Litigation Reform Act of 1995

Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization; the impact of competitive products, including, but not limited to the impact of those on Shire’s Attention Deficit and Hyperactivity Disorder (“ADHD”) franchise; patents, including but not limited to, legal challenges relating to Shire’s ADHD franchise; government regulation and approval, including but not limited to the expected product approval dates of SPD503 (guanfacine extended release) (ADHD) and SPD465 (extended release triple-bead mixed amphetamine salts) (ADHD); Shire’s ability to secure new products for commercialization and/or development; Shire’s ability to benefit from its acquisition of New River Pharmaceuticals Inc.; and other risks and uncertainties detailed from time to time in Shire plc’s filings with the Securities and Exchange Commission, particularly Shire plc’s Annual Report on Form 10-K for the year ended December 31, 2006.

Moorfields hospital carries out world's first gene therapy operation to cure blindness

BBC News has learned that a team at Moorfields Eye Hospital in London has carried out the world's first gene therapy operation in an attempt to cure blindness in children and young adults.

BBC Science Correspondent, Pallab Ghosh, has had exclusive access to the patient and the doctors involved in this pioneering operation.

The procedure was carried out on Robert Johnson, a man who was born with a sight disorder which becomes worse with age. At the moment he can see outlines during the day – but very little when it's dark. As he gets older his vision will become progressively worse.

Robert told the BBC that he hoped that that might change. He is the first person in the world to take part in an attempt to treat blindness using gene therapy. Doctors at Moorfields Eye Hospital have inserted genes into one of Robert's eyes in the hope that his sight might recover.

On the day of the operation Robert revealed that he had mixed feelings: "It's very difficult to say how I'm feeling, I keep ranging from extreme nervousness to a bit of excitement."

Robert wasn't the only one who was nervous. His feelings were shared by the lead researcher, Professor Robin Ali, who has spent 15 years working with colleagues developing the technique.

As Robert was being prepped for his operation, Professor Ali was anxiously waiting in his office at the Institute of Ophthalmology: "I can't help feeling somewhat apprehensive, there's so much riding on it and we've all been waiting for a very long time."

Robert's disorder is an inherited disorder, caused by a faulty gene called RPE65. This defect stops the layer of cells at the back of the eye from working.

The operation involves injecting working copies of the genes into the back of Robert's eye, underneath the retina which contains the cells that normally detect light. But in Robert's case it's these cells that are damaged and stop him from seeing properly.

It is hoped that the replacement genes will enable the retina to detect light – and eventually improve Robert's sight.

The technique has worked in the lab and it has worked on animals. Asked if he thought it would work on Robert, the surgeon carrying out the operation, James Bainbridge, said: "We intend to find out during this experimental procedure. We don't know for sure how someone like Robert's retina is likely to behave in this situation."

During the operation, James Bainbridge injected normal copies of the gene into the back of Robert's eye. It required incredible precision on the surgeon's part. One slip and Robert's retina would have been torn. The operation would have failed

Asked how it went, assisting surgeon, Robert Maclaren said: "Extremely well," whilst beaming through his surgical mask.

"We couldn't have asked for a better result. In fact if I sat and drew what the perfect result would have been on a piece of paper – the retina would have looked pretty much as it would look now."

It will be several months before we know if the operation has worked on Robert. He's the first of 12 young people trying out the new technique. If it is successful, the researchers believe that it could be used to treat a wide range of sight disorders.

Daily Steroid Helps Boys With Duchenne's to Walk

WEDNESDAY, May 9 (HealthDay News) -- Long-term daily steroid treatments helped boys with Duchenne muscular dystrophy walk on their own for a longer period of time and reduced their risk of scoliosis, an Ohio State University study found.

Symptoms of this condition, which affects about one in 3,500 boys, begin in early childhood and rapidly progress. Most patients lose the ability to walk by between ages 9 to 11. There is no cure.

Researchers reviewed the medical records of 143 boys with Duchenne muscular dystrophy treated at the university's Muscular Dystrophy Clinic in Columbus. Of those boys, 75 had received daily treatment with corticosteroids for an average of eight years, while the remainder had received only a brief dose of steroids or none at all.

The boys who received the long-term daily steroid treatment walked by themselves 3.3 years longer and had a lower rate of scoliosis (31 percent vs. 91 percent) than untreated boys, the study found.

But the researchers also found that boys who received daily steroid treatment were more likely to suffer vertebral fractures than (32 percent vs. 0 percent), and were 2.6 times more likely to suffer a leg fracture than untreated boys.

This may be due to increased body weight and the fact the treated boys walked longer than untreated boys, the researchers said.

"The benefits of steroids come at a cost of the side effects, and patients and parents need to weigh the benefits and risk of steroid treatments in order to make an informed decision," study author Wendy King, of the neurology department at Ohio State University Medical Center, said in a prepared statement.

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