6 min

Hopes for new treatment of congenital brain disorders

About one in a thousand children is born with an impaired metabolism. This often results in brain damage. Anna Wedell has made a hi-tech genetic survey that has revealed the molecular basis for several of these disorders. In one case this new knowledge resulted in a marked improvement in the health of a small child.

Anna Wedell

Senior Physician and Professor of Medical Genetics, Karolinska Institutet

Wallenberg Clinical Scholar 2015

Principal research field:
The molecular basis for congenital, hereditary metabolic diseases in children.

“Congenital metabolic disorders result in many hundreds of unusual conditions. These disorders are often due to hereditary impairment of the body’s chemical reactions. The brain is particularly sensitive, although most organs can be affected,” explains Professor Wedell, who is a senior physician and Professor of Medical Genetics at Karolinska Institutet.

“Common symptoms are late development, epilepsy or acute conditions that may cause premature death. Many congenital metabolic disorders are treatable if caught early, before irreparable damage occurs.”

A PKU test is a blood test that can reveal 24 different congenital disorders, all of which are treatable. All new-born babies are tested for PKU. But there are several hundred known forms of metabolic impairment, for many of which there is still no effective treatment. Also, there are many diseases where proper statistical information is still lacking. As a Wallenberg Clinical Scholar, Professor Wedell will be continuing her detective work as she delves deeper into the causes of these diseases.

Technical revolution

“Diagnosis of hereditary disorders is being revolutionized now thanks to new methods of analyzing DNA. My research team has developed a method for swift and reliable diagnosis of all known monogenic diseases, a revolution for those families affected, who can now receive the right diagnosis and treatment at an early stage of the disease.”

Monogenic disease is the name given to a disease caused by a single defective gene. One such disease is phenylketonuria, which was the disease for which the first PKU tests were created.

Professor Wedell and her team want to transform diagnostics for congenital metabolic disorders, which represent 10–15 per cent of monogenic diseases.

“Quite simply, we want to discover new diseases, identify disease mechanisms and develop new treatments for sufferers.”

Professor Wedell believes they have good prospects of success.

“We have been saving unique patient material for many years. We have also created a strong interdisciplinary environment in which we combine technical, genetic, biochemical and clinical expertise. I think we have a unique opportunity to translate our basic scientific discoveries into immediate benefit for our patients.”

Ground-breaking treatment

The research team has already presented new findings.

“We have discovered a number of completely new diseases. The children with these disorders had all undergone prolonged investigations over many years without result. The new findings have had a number of positive effects. The families have been told what has caused their children to suffered serious brain damage. And we have learnt a great deal about how the damage is caused at molecular level, which has in turn improved our knowledge about the way the brain works.”

There was great elation when Professor Wedell’s team’s research resulted in a treatment that improved the brain function of a young girl with serious brain damage.

“Based on the disease mechanism we had identified, we devised a specific dietary treatment for the patient. The result was a dramatic improvement in the little girl’s condition,” Professor Wedell says.

She explains that the dietary treatment was able to compensate for the metabolic defect. As a result, the brain resumed production of myelin – the “white matter” of the brain.

“No treatment had previously been found to improve myelination, and the breakthrough is therefore of great importance,” Professor Wedell points out.

She believes that several diseases and disorders are rooted in metabolic defects.

“Diseases of the mitochondrial respiratory chain are of particular interest, since impairment of the chain’s function is involved in several common degenerative diseases of the nervous system, such as Parkinson’s and Alzheimer’s. By identifying the mechanisms behind uncommon hereditary diseases, and by studying models of those diseases, we will also be able to understand the metabolic components behind more common diseases. This will ultimately lead to new treatment principles.”

Text Carina Dahlberg
Translation Maxwell Arding
Photo Magnus Bergström

 

24 CONGENITAL DISORDERS DISCOVERED

Since the mid-1960’s the PKU test has been performed on all new-born children in Sweden as soon as possible after 48 hours from birth. The aim is to find a number of uncommon diseases whose early treatment is vital. Originally, the test results revealed five disorders, but since 2010 a further 19 can be identified. Approximately 50 out of the 100,000 or so children born in Sweden each year have one of these disorders.