New drug holds out promise of normal diet for sufferers of devastating PKU genetic disease
Severe protein restrictions normally the only way to avoid brain damage and retardation
Imagine being forced to say no to a child crying for more food at supper. Sadly, Margie Fischer doesn鈥檛 have to imagine it; that was normal life at her family鈥檚 dinner table for years. Her daughter Maggie, now 20, suffers from phenylketonuria (PKU), a genetic disease that means her body can鈥檛 tolerate anything more than a low-protein diet.
PKU is described by scientists as an autosomal recessive genetic disease that is characterized by a deficiency in an enzyme called phenylalanine hydroxylase (PAH).
Without PAH, the body cannot metabolize the amino acid phenylalanine. It then builds up in the blood, crosses the blood鈥揵rain barrier and causes severe brain damage. Fortunately, PKU can be detected at birth in blood tests, and was one of the first treatable genetic diseases. From infancy, PKU sufferers are restricted to a low-protein diet to avoid the worst complications of the condition. This diet is essential during childhood to prevent damage to the brain while it is still growing; however, it is now also recommended for life to optimize school performance, concentration and the ability to think clearly.
"When Maggie was a little child, we would give her vegetables and we could give her, say, two little sprigs of broccoli," Fischer said. "She would be crying at the dinner table that she wanted more broccoli," Fischer said. "Saying no to a kid who wants more broccoli brought tears to my eyes. It was so sad."
However, help may now be on the way. A new pharmaceutical being developed by researchers at 捆绑SM社区 and the 捆绑SM社区 University Health Centre (MUHC) 鈥� along with colleagues at the Scripps Research Institute and BioMarin Pharmaceutical Inc. 鈥� is offering PKU sufferers the hope of being able to eat a normal, protein-rich diet. Their preclinical evaluation study was published in December in the Proceedings of the National Academy of Sciences.
"The problem is that the PKU dietary modification is extreme," said study first-author Dr. Christineh Sarkissian, a research associate at 捆绑SM社区鈥檚 Departments of Biology and Human Genetics and the MUHC/Montreal Children鈥檚 Hospital Research Institute. "It鈥檚 not a lifestyle choice, it鈥檚 an obligation, and it鈥檚 very difficult."
"Maggie needs to eat a special diet which consists largely of drinking an amino acid formula that鈥檚 very nasty and gritty," Fischer explained. "She can鈥檛 eat meat, nuts, fish, dairy or grains. And when I say grains, that means no pasta, no bread, no crackers, nothing. So for example, when a typical teen goes out and has a cheeseburger, Maggie can鈥檛 have the cheese, the meat or the bun. She can have the lettuce and the pickle."
Even individuals who have lived on the restricted PKU diet for years may still suffer health effects into adulthood, Sarkissian explained, especially if they increase their protein intake as they get older.
"The majority of adult PKU patients, depending on how sensitive they are at the blood-brain barrier, will end up suffering from agoraphobia and other reversible conditions that can result from insult to the brain," she said. "The majority of kids who go on to university need to remain on the diet, otherwise they just can鈥檛 function clearly."
Sarkissian is hopeful that the new injectable treatment she developed with her former supervisor and now colleague, the corresponding author Dr. Charles Scriver - Emeritus Professor of Pediatrics and their academic and industrial collaborators - will make it possible for PKU patients to eat a more normal diet.
"As we go into clinical trials, we鈥檒l see how it works in humans," she said. "Certainly in the animal models we showed that the phenylalanine levels came down to normal. The treatment itself is enzyme therapy, so patients will receive an injection once or twice a week instead of, we hope, needing to be on the diet."
"I鈥檝e got high hopes about this research," said Fischer. "I couldn鈥檛 be more excited. It would change Maggie鈥檚 life in two ways: From her point of view, I鈥檓 sure the most important thing would be the less restricted diet. She鈥檚 hungry a lot of the time, she never gets enough food to fill her. She would be excited to eat all the cauliflower she wants, or a whole banana. She鈥檚 never eaten a whole banana!"
"Aside from just the diet portion," Fischer added, "PKU affects mood and the ability to concentrate, and diet therapy does not work perfectly for everyone. What means the most to me is that the new treatment would allow Maggie to reach her full potential."
ABOUT McGILL UNIVERSITY
捆绑SM社区 , founded in Montreal , Que., in 1821, is Canada 鈥檚 leading post-secondary institution. It has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 33,000 students. 捆绑SM社区 attracts students from more than 160 countries around the world. Almost half of 捆绑SM社区 students claim a first language other than English - including 6,000 francophones - with more than 6,200 international students making up almost 20 per cent of the student body .
ABOUT THE RI MUHC
The Research Institute of the 捆绑SM社区 Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal , Quebec , the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at 捆绑SM社区. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge.
The Research Institute of the MUHC is supported in part by the Fonds de la recherche en sant茅 du Qu茅bec.
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