Zach-Attack.org

Zach Pickard, not quite 3 years old, leans over a Dora the Explorer toy, a little over 3 inches tall.

"Say cheese," he orders the little plastic girl, an early Christmas present, taking a fake picture with the light of a toy miner's hat.

This is the first Christmas season in which Zach can discuss the holidays: He can flip the switches to all manner of noise-making gadgets, such as musical snow globes and a train that circles the Christmas tree in his family's house in South Lexington. He chatters about cartoon characters: SpongeBob SquarePants and his conical friend Patrick. Dora and Diego.

A full recounting of the subtleties of the Nativity, with Mary, Joseph and the wise men, might have to wait until next year.

Zach has progeria, a premature aging disease. When he was born, he looked like a healthy, chubby infant  6 pounds, 14 ounces. But his family quickly noticed bumps that made him different from other babies. A pediatric dermatologist in Cincinnati suggested testing for progeria. Zach was diagnosed with the disease in December 2007; he was less than a year old.

His father had seen a show about progeria on TV. His mother had never heard of it.

Progeria, at its most basic, is a disease about cell deterioration. The disease robs cells of their biological scaffolding, so they deteriorate more quickly.

Progeria children generally start displaying symptoms when they're 18 to 24 months old. Zach is 35 months old. In January, he'll celebrate his third birthday with a pizza party at Chuck E. Cheese.

Worldwide, the disease affects one in 4 million children. There are now only 54 children worldwide with progeria.

Zach and 14 other children in the United States have progeria, although Audrey Gordon, director of the Massachusetts-based Progeria Research Foundation, thinks there are probably as many as 100 to 150 children worldwide who have progeria but have gone undiagnosed.

Zach is one of 45 children from 30 countries who are participants in a three-drug trial for progeria patients, a trial that Zach's mother, Tina Pickard, hopes will help Zach live a long, healthy life. Results from an earlier drug study will be released this spring, but it might be years before results from the newer, three-drug study are released. The study ends in 2012.

"We're equally if not more excited about the triple-drug trial," says Gordon. "Because (the drugs) all deal with different parts along the pathway, so instead of attacking one area, it's attacking three."

The Progeria Research Foundation (www.progeriaresearch.org) is putting its hopes in the drug research trial. The drug, part of a class of experimental anti-cancer drugs, farnesyltransferase, or FTI, blocks attachment of the progerin protein.

For now, being part of a drug trial is part of a game for Zach. When you're 2, most everything is part of a game.

"He thinks that we're joking play partners all the time," says Zach's dad, Brandon Pickard.

Being nearly 3 years old and chatty is beneficial to Zach in that he can now conduct the rudiments of his own interviews.

Where do you fly for the drug trial, Zach? "Boston!" What does the plane sound like? "Zoom!"

He is tiny but, like many kids his age, clearly in charge of the household. When he's happy, the routine hums along. When he's hurt or mad or doesn't understand why an audiotape cassette can't go into a VCR, things are less placid: Toy cars litter the kitchen floor, and yogurt branded with the image of SpongeBob, along with macaroni and cheese, served in a special bowl with a special spoon, is on the menu.

"He is like a typical 2-year-old," says Tina Pickard. "Everything used to be a struggle and fight, but he's getting much better."

Zach is about 21 pounds and just under 22 inches tall. His blonde hair is largely gone now. Progeria kids lack insulating fat to cushion them from temperature extremes and falls, so routine toddler actions  falling on a floor, crashing into a shelf  sting Zach more than they might other children.

Still, Zach has progressed on many fronts: He has learned to negotiate the stairs on his tiny legs, and on a level floor he is a whirlwind of toddler mischief.

Recently Zach was glimpsed on a special on The Learning Channel  6 Going on 60, a one-hour documentary about two girls with progeria: Kaylee Halko, 6, of Ohio and Lindsay Ratcliffe, 5, of Michigan. One of the distinguishing marks of progeria is that children who have it look like siblings. They are all smaller than other children, and progeria kids lose their hair, often have abnormalities in their teeth and have stiff joints. Their expected life span is short. Whether the drugs now being studied will change that permanently is not known.

So: Christmas. This is the first Christmas that Zach can actively express what he wants: toys. To throw, with an uncannily accurate arm, jingle bell ornaments across the room  "Daddy, watch it!"  and laugh a trilling laugh that is somewhere between a purr and a holler. Zach also likes to "fly on a boat," which is the name he made up for a game in which he is balanced on the outstretched legs of his sister Brittany Banahan, 16, a junior at Lafayette High School.

Zach's mother knows that not every Christmas might be this hopeful. Still, she and Brandon don't give up on their boy, ever. "It's not a medication that's going to make him grow," Tina says of the drug trial. "It's not a medication that's going to make his hair grow."

But the medical trial might buy time, and health, and many more Christmases.

And that, in the glow of the Christmas tree, seems enough to ask.