Deferred Hope for Dementia Sufferers

The day I had been dreading came in the spring of 2000, about three years after my mother’s diagnosis with Alzheimer’s disease. She sat in my house and tearfully announced that she did not know who I was or where she was. When I introduced myself, she apologized, saying she must have been a terrible mother. It took me a moment to follow her line of thought: Because she had no memory of me, she assumed that we were estranged and that she was seeing me for the first time in decades. But she was still Mom -- sweet-faced, gentle under stress, articulate even in her confusion.

That was her last visit to California. By the time I flew east several months later, my mother was barely recognizable. Her face fixed in a scowl, she shuffled aimlessly around the house she had lived in for 52 years, occasionally muttering in a harsh monotone. Only by giving her a potent anti-psychotic drug was my father, her husband of 60 years, able to keep her from walking out the door to “go home.”

Clearly, the drug Aricept, which she had taken to slow the disease’s progression -- and the alternative treatments and top doctors my sister, Lynn, had tirelessly unearthed -- hadn’t kept Mom from reaching this phase within four years of diagnosis. Two months later, the Alzheimer’s specialist would tell my sister and father that he had nothing left to throw at the illness. Except ...

He had been participating in the U.S. trials of a drug used in Europe. Studies had found real results. The Food and Drug Administration hadn’t yet approved the drug for sale here, but it was possible to buy it legally through certain channels with a prescription. He couldn’t write one, though. It would be unethical for a doctor involved in the research.

To Lynn, words like that are a mild obstacle to be scaled -- or smashed through, if necessary. She found another doctor to write the prescription and located an overseas pharmacy to fill it. In April 2001 my mother took her first doses of memantine.

By that time, she was incontinent and couldn’t feed herself. She seldom walked but would sit and stare for hours, except for increasingly angry outbursts. At my father’s birthday party two weeks earlier, she had sat, slumped and silent, until my brother, sitting next to her, made some innocuous comment she didn’t like. Then she stabbed his hand, hard, with her fork.

Within two days of the first memantine dose, the family noticed that Mom was far more alert and was able to accomplish everyday tasks such as brushing her teeth. Three weeks later, she dressed herself in evening clothes and attended a big black-tie bash to celebrate Lynn’s 50th birthday. Mom sat at the table and ate dinner, by herself, with utensils. She danced much of the night away with Dad, one of their favorite activities dating back to their teenage years. She smiled and socialized.

“I don’t think anyone realized there was anything wrong with her,” Lynn said. “That was the most amazing miracle -- and the best birthday present I could have gotten.”

I’m glad Lynn got her miracle, but memantine is no miracle drug. It has not brought my mother back to her intelligent, thoughtful self, but it has helped, and for this we are grateful.

Memantine does not cure Alzheimer’s disease, return patients to normal or put them in remission, and it doesn’t work for everyone.

But for many patients, the drug has a measurable and sometimes profound effect, restoring for a time mental functions that had seemed lost forever and easing the exhausting workload for caregivers. It can give people a long step back from the disease’s otherwise inexorable march toward disability and death.

The drug works by blocking the brain chemical glutamate, which in excess amounts allows too much calcium to enter cells, causing cell disruption and cell death. Memantine has been used in Germany for 15 years, first to treat Parkinson’s disease and later glaucoma, AIDS- related neuropathy and Alzheimer’s. The European Union approved its use to treat Alzheimer’s in May 2002.

Memantine slows the progression of moderate to severe Alzheimer’s, according to a study published in the New England Journal of Medicine this year. Another study, not yet peer reviewed, found that patients who took it as part of a combination therapy with Aricept regained abilities they had lost. None of the studies has found serious side effects.

So why is the drug’s availability so limited in the U.S.?

Forest Laboratories gained the U.S. rights to market memantine in 2000. Since then, the company has been going through the exacting process of filling out forms, following procedures and conducting experimental trials the FDA requires. Delayed by one problem or another, Forest filed its full application in December. The FDA is expected to respond -- with approval, rejection or a request for more information -- by the end of the year. The earliest Forest expects the drug to be on the market is the first half of 2004.

The FDA has the option of “fast-tracking” a drug application, meaning officials can work with the drug company to help bring a medication to market quickly if it is for a serious illness and there is no similar treatment available. This year, the FDA fast-tracked a potential weight-loss treatment. Meanwhile, memantine, which the Alzheimer’s Assn. calls the only drug to show promise for the treatment of advanced Alzheimer’s, is still slogging its way through the standard approval process. Forest says it made clear to the FDA that it thought memantine was a candidate for fast track, but that the agency chose not to accelerate the process. The FDA will not comment on pending drug applications.

That leaves the families of patients seeking the drug with few options. Some savvy people, like my sister, work within the FDA’s “personal use importation” policy, which allows individuals to purchase a foreign drug to treat serious illnesses if that drug is approved in another country and if no comparable medication is available in the U.S. But because the drug cannot be sold commercially in this country, finding a vendor can be difficult. One major Internet supplier, overwhelmed by demand, is taking no new customers for memantine.

In addition, the FDA’s personal-use policy, which AIDS patients and their advocates lobbied for, requires patients to get a prescription from a doctor. But since most doctors remain unfamiliar with memantine and will not write prescriptions until it passes muster with the FDA, patients who might benefit from the drug cannot obtain it. Though no one knows how many Alzheimer’s patients in the United States take the drug, the number is believed to be less than one-half of 1% of the estimated 4.5 million Americans with the disease. On the Internet, Alzheimer’s chat rooms hum with the names of online pharmacies where people can buy the drug illegally, without showing a prescription. But many elderly people quail at the thought of circumventing authority. (“I’m younger; I can handle whatever the FDA does to me,” said a defiant Hermosa Beach woman who illicitly bought memantine for her mother and noticed marked improvements in her abilities.)

The agonizing wait makes no sense for this drug and this disease. An Alzheimer’s diagnosis sentences people to years of diminishing mental and physical abilities, until one day their ravaged brains no longer signal their bodies to eat or breathe. It’s hard to imagine what people like my mother, who was shuffling unhappily through the unfamiliar rooms of her life toward bedridden deterioration, have to lose from a drug that Europeans can readily obtain.

The news about memantine came to Gwen Roberts in the form of a newspaper clipping sent by a friend. The 70-year-old Eureka resident takes care of her husband, Bruce, who was diagnosed three years ago. By April, he hadn’t put pen to paper in two years. Like many Alzheimer’s patients, he hated getting near water. Phone conversations consisted of his grunting once or twice into the receiver.

Roberts hopped on the Internet and read everything she could find about memantine. She asked her husband’s neurologist about getting him into one of the trials, but they were closed. The neurologist was rare among American doctors. He would write a prescription.

Bruce Roberts received his first doses in early May and experienced dramatic changes within days. The man who would put up a “bloody fight” to avoid water now cheerfully showers by himself. Previously incontinent, he takes care of his own toileting. He’s written a few things. He had a complete, though simple, phone conversation with his grown daughter, at one point telling her, “I love you.”

“Things have come back that we never expected to see again,” Gwen Roberts said.

Dr. William Shankle makes similar observations. The Irvine Alzheimer’s specialist has been prescribing memantine for two years, to about 200 patients so far. The drug has few and mostly mild side effects, he said, and does not have bad interactions with most other medications.

Then there are the “extraordinary improvements” Shankle has seen in many patients. Some, once confined to wheelchairs by Alzheimer’s disease, walk unaided. Others wore adult diapers that they don’t need now. Or they had stopped talking, but now communicate again.

Fred Krumm of Toledo, Ohio, heard about memantine three years ago on an Internet business broadcast. Though his wife is the one with Alzheimer’s, the 85-year-old man talks about the disease as a shared event.

“When we were diagnosed 13 years ago,” he said, “we came home and cried and cried, and then decided we were going to do everything we could do to fight it.”

The family’s physician refused to prescribe memantine, so Krumm sent letters to dozens of doctors within a 60-mile radius. Two responded. He filled the prescription at a nonprofit drug-buying club in New York that formed 10 years ago to help AIDS patients. He saw no improvement in his wife’s abilities but thinks memantine might have slowed her deterioration.

Dorothy Krumm still can walk and converse. But she entered a nursing home last month because of a blood clot and increasing frailty.

The FDA has been rightly criticized for approving some dangerous drugs too quickly. It needs a better sense of priorities -- when to be cautious, when to move aggressively. My mother also is diabetic, but we never considered using experimental drugs for her diabetes. There were other treatments available, and my mother could live many happy years with diabetes.

It doesn’t take a medical brain to see that the FDA’s rules of conduct look downright silly in the face of diseases like Alzheimer’s. Once past the early stages of the disease, Alzheimer’s patients and their families have nothing to hope for except an occasional better-than-average day.

And as risk-averse as the FDA might be, patients and families are deciding that, whatever the medical establishment might say, there are worse options than taking a chance.

My mother did well on memantine until a massive, unrelated infection threw off her blood sugar and brought her close to diabetic coma. This physical assault put her into a tailspin that landed her permanently in a nursing home. Many of the gains she had made were lost. She walked only occasionally and had to be fed again. She often would speak gibberish.

But her condition has not deteriorated in the year and a half since. Now, at 82, she is generally happy and loving, socially appropriate with people and occasionally able to fling out a wicked line of humor. The nursing home will not give her an unapproved drug, but because she has a prescription, it allows family members to administer memantine. That’s OK. My father visits her every day, anyway.