New drug may ease genetic disease Kuvan broadens some PKU diets

BANGOR – For a small group of Mainers and other people with a rare genetic disorder, life just got a little more appetizing. The Food and Drug Administration’s recent approval of the new drug Kuvan promises to open new dietary horizons for children and adults afflicted with phenylketonuria, or PKU.

People born with PKU lack an enzyme that rids the body of excess levels of the amino acid phenylalanine, a protein component contained in many common foods. Unless the condition is diagnosed shortly after birth and managed aggressively throughout life, phenylalinine, or Phe, builds up quickly in the blood and irrevocably destroys brain cells.

The most common and devastating symptom of PKU is profound mental retardation, which develops in the great majority of those who go untreated. Other neurologic symptoms include seizures, hyperactivity and psychosis. These consequences can be avoided only by keeping Phe levels consistently low across the life span.

For most people, a diagnosis of PKU means a lifetime diet of a narrow group of approved fruits and vegetables and a pricey synthetic formula that looks like drywall primer and tastes like the inside of a fruit-flavored vitamin pill. Dairy products, nuts, fish, dry beans, many breads and cereals, and a surprisingly comprehensive list of common produce items are all off limits.

Above all, individuals must avoid foods that are rich in proteins.

“The aim is to have kids think that this diet is normal,” Bangor geneticist and pediatrician Dr. Stephen Amato said Friday. “We want them to think that meat is disgusting. Dead flesh. Carrion.”

Even the most motivated patients who manage to adhere to the unappealing diet often have trouble keeping their Phe levels within the therapeutic range, he said. For children and teens, especially, he said, it can be extremely difficult to ensure compliance – too often, with life-altering consequences.

So Amato is optimistic that Kuvan, which he has been using for several months in a clinical trial with just four of his patients, will be “liberalizing” for at least some individuals.

Among them is 37-year-old Heather Gerquest of Bangor. Gerquest has “atypical PKU” – her body produces a small amount of the enzyme needed to break down and excrete phenylalanine.

“My diet’s not as strict as some people’s,” she said. She can eat a somewhat wider variety of foods, though almost 70 percent of her daily nutrients still come from the dreaded PKU formula.

“It’s really nasty,” she said, grimacing.

Especially since her husband is a professional chef, Gerquest said, she often feels “deprived” of interesting foods.

“Kuvan allows me to eat more protein. It increases my selection a lot,” she said. “People don’t realize that even things like bananas and broccoli, a slice of bread, lots of green vegetables, even lettuce – they all have protein in them.”

Kuvan works by stimulating the enzyme that breaks down phenylalanine. Since Gerquest’s body naturally produces a little bit of that enzyme, the medication is effective at keeping her Phe levels in check, Amato said, even when she pushes the envelope of her diet restrictions. Continued weekly monitoring of her Phe levels will be essential, he stressed.

For three other patients with “classical” PKU – no enzyme production at all – Kuvan failed to maintain acceptable Phe levels when diets were liberalized, Amato said, although they all reported feeling less “fuzzy” mentally.

Biomarin, the company that manufactures Kuvan, cautions that not all patients with PKU will respond, and that Kuvan does not eliminate the need for careful dietary management and regular monitoring of Phe levels. The drug may cause a number of adverse side effects, some of them serious. And it remains to be seen how willing insurance companies will be to cover the medication.

But for an intractable disease that until now has had no effective treatment other than a lifetime of dietary deprivation, Amato said, Kuvan offers the first real improvement.

More information about Kuvan is available at www.kuvan.com.

More information about PKU can be found at the Web site of the Mayo Clinic, www.mayoclinic.com.

Meg Haskell may be reached at mhaskell@bangordailynews.net or 990-8291.