Research News

Welcome to the National Information and Advice Centre for Metabolic Diseases Research News Sheet.

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.

World’s first microchip being developed to screen embryos

Researchers from the Monash Institute of Reproduction and Development and the Monash IVF in Victoria, Australia are in the process of developing a world first microchip that can be used to screen embryos for all genetic disorders. The chip will be able to test embryos simultaneously for all known genetic conditions.

The technology may also be used in conjunction with pre-natal practices such as amniocentesis to screen for diseases in foetal cells collected from pregnant women.

The microchip will store genetic data, which can be compared with the gene sequences in an embryo cell sample to identify any defects.

The charity Cerebra for brain injured children and young people have just awarded a £104,000 grant to Professor Chris Harris and his team at the University of Plymouth to develop the measurement of eye movements in infants and young children with neurometabolic diseases.

Metabolic medicine is entering a new era of realistic drug therapies for the first time. The introduction of enzyme replacement therapy (ERT) ten years ago has been a dramatic success for most children with Gaucher disease. Although these are astonishing positive developments, it cannot be taken for granted that new therapies will also stop or reverse brain damage. This means that new drugs will also need to be tested for their effects on halting brain damage. It also means that new therapies will need to be started as early as possible before irreversible neurological deterioration become severe. The problem is how to measure brain function in the very young child or infant.

The goal of the 2-year research project is to develop new methods for quantifying eye movement abnormalities in young neurologically impaired children. Eye movement abnormalities are important because they can be an early sign of brain involvement. They can also affect how well a child uses his/her vision, and can affect education. In older children and adults eye movements can be measured accurately, but in young children and infants it is not so easy. There are limitations on the type of equipment that can be used, and infants and young children, particularly when they are ill, do not follow instructions. Fortunately, infants are born with certain eye movement reflexes. The project will focus on measuring these types of movements as they can be elicited easily from any child or infant without the need to follow instructions.

Chris and his team are looking for young volunteers with neurometabolic diseases for this project. If your child has one of the many metabolic diseases which affect the brain, and you would like have your child’s eye movements assessed please contact Chris. He has many years experience in recording eye movements from young children, and the procedures are quite safe and non-invasive (some of you will have met the team because of the OGT918 (Zavesca) trials, or will have met him when he worked at Great Ormond Street Hospital). Expenses will be paid for families to travel to Plymouth including overnight hotel stay and meals.

Expandable Rib approved in US and European Union as aid for young people with chest or spine deformities

Since 1992, clinical trials have been undertaken by Dr Robert Campbell of the University of Texas to study the effectiveness of a titanium artificial rib for children with rare deformations of the chest and spine. The titanium rib is made so that it can be expanded as the child grows. Children with these deformities do not have a lot of room in their chest and often die because the lungs cannot expand and the child is unable to breathe properly. The titanium rib is known as the Vertical Expandable Prosthetic Titanium Rib (VEPTR). It is able to accomplish a more normal growth pattern, decreased chest, spine and rib deformity, expanded lung volume, increased life span, decreased dependence on a supplemental air supply and increased physical activity.

The results of the study were positive and Dr Campbell won government grants and studies were completed on 147 children aged six months to 15 years old. These studies proved that the titanium rib was safe and effective. In 2004, the US Food and Drug Association (FDA) approved the rib under a “Humanitarian Device Exemption” (HDE) this is a category of FDA approval for rare disorders that affect fewer than 4000 people a year in the US. A medical device manufacturer known as Synthes Spine Company in Pennsylvania now produces the VEPTR.

Genzyme Corp. announced today that the European Medicines Agency (EMEA) has accepted its marketing authorization application for Myozyme® (alglucosidase alfa), an investigational enzyme replacement therapy for Pompe disease.

If approved, Myozyme would become the first treatment available to patients with Pompe disease, a debilitating and often fatal muscle disorder resulting from an inherited enzyme deficiency.

The EMEA's Committee for Human Medicinal Products is expected to issue an opinion on the Myozyme application within one year, and a decision by the European Commission is anticipated early in 2006.

At the end of December, BioMarin Pharmaceutical Inc announced that it had taken the first step in its Phase 2 clinical trial of Phenoptin™ (sapropterin hydrochloride also known as 6R-BH4). Phenoptin ™ is an investigational oral, small molecule therapeutic primarily being tested for the treatment of moderate to mild forms of phenylketonuria (PKU).

Up to 400 patients diagnosed with PKU will be screened for a positive response to Phenoptin™ as defined by a 30% or greater reduction in blood Phenylalanine levels. PKU patients over the age of 8 will receive 10mg/kg of Phenoptin ™ daily for eight days. Responsive patients will be eligible to enrol in the Phase 3 clinical trial expected to begin in 2005.

A rare, previously undiscovered genetic disorder has been identified by researchers. The disorder was named after Dr Katherine W Timothy who identified a child with the then nameless disorder in 1989. Timothy Syndrome, also known as Long QT Syndrome with Syndactyly, is often fatal by the second year of life but may be treatable with calcium channel-blocking drugs.

Findings of the disorder were reported in the October 1^st Issue of Cell. The disorder is characterized by heart problems, webbed hands and feet and a weakened immune system. Timothy Syndrome may also cause a form of autism in individuals.

It is unknown how many children are affected by the disorder, researchers have so far identified 17 children with the disorder, however more are expected to be diagnosed as medical professionals learn about the disorder.

In November, BioMarin Pharmaceutical Inc submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) and in December announced that they had also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency for an investigational therapy known as Aryplase ™.

Aryplase ™ (galsulfase) is an enzyme replacement therapy under investigation for the treatment of MPS VI (Maroteaux-Lamy Disease). It is designed to address the underlying deficiency of MPS VI and provide N- acetylgalactosamine 4-sulfatase (arylsulfatase B), the enzyme that people with the disorder are lacking.

Aryplase ™ has received fast track status and orphan drug designation in the US and European Union. Orphan drug designation is conferred upon investigational products for diseases that affect fewer than 200,000 people in the United States or 10,000 in the EU. Products with orphan drug status that are the first to be approved for a specific indication have seven years of market exclusivity within the United States and 10 years within the EU.

In the past nine years, Dr Paola Leone of the Robert Woods Medical School in New Jersey has conducted two experimental trials using brain gene transfer of the Aspartoacyclase (ASPA) gene, the defective gene in Canavan Disease.

Dr Leone followed the disease progression in the 10 affected children who had taken part in the trial and other children who had not. The trial was proven to be successful and tests showed significant improvement in all the children. Improvements in cognitive and motor function were observed, some were even able to coordinate with both hands, which was regarded as a great success. As expected, the outcome was comparatively better in younger children. Dr Leone said she had acquired an enormous amount of knowledge about the disease and a phase II clinical trial is being planned to test the efficacy of the treatment in a larger group of children.

Dr Leone has also been working for many years with professors at the at the New York University in the effort to identify novel Canavan disease defects in the non-Jewish population.

Molecular Patches restores production of essential protein in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by errors in a gene that affects the production of an important muscle protein known as dystrophin. Studies have shown that the injection of 'molecular patches' (antisense oligonucleotides) can modify the faulty genetic code.

The new technique aims to insert a ‘molecular patch’ over the gene defect that causes Duchenne muscular dystrophy, to restore the production of the muscle protein. This will be achieved by injecting the ‘molecular patch’ directly into the muscles. The process is predicted to reduce muscle disease significantly to levels similar to Becker muscular dystrophy (BMD), a related genetic condition that is considerably milder and allows far greater quality of life.

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Current research is ongoing to develop a better understanding of what happens once the defect in the fibrillin gene that causes Marfan Syndrome occurs. Scientists are searching for reasons why it changes the way connective tissue develops and functions in the body and why some people with Marfan syndrome are affected differently to others.

This will be achieved by investigating the defective genes and by studying families who are affected by the disorder. Mouse models have been developed that carry the defects in the fibrillin gene. These mice may help scientists gain a better understanding of Marfan Syndrome. Preliminary investigations into gene therapy are also under way.

Scientists are also currently studying ways to treat some of the complications that arise in people affected by Marfan syndrome. Researchers are working to develop new surgical procedures to help improve the cardiac health of those affected by Marfan syndrome and studies are ongoing to evaluate the usefulness of certain medications in preventing or reducing problems with the aorta.

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