July 05, 2002
Steve Mitchell, UPI Medical Correspondent
United Press International
In the 10 years since the release of the film "Lorenzo's Oil," scientists have made significant strides in understanding, treating perhaps curing the rare, deadly illness known as adrenoleukodystrophy that is the focus of the film -- progress that may help others suffering from illnesses with similar causes.
The film depicts the true story of a boy, Lorenzo Odone, stricken with adrenoleukodystrophy or ALD, who appears to improve after receiving an experimental compound discovered by his parents. The compound came to be known as Lorenzo's Oil.
Despite the positive results in the movie, however, Lorenzo's oil -- made up of two fats from olive oil and rapeseed oil-- subsequently proved ineffective in treating ALD in scientific studies.
But the oil may prove effective for preventing the disease. Scientists recently finished a new study examining just that possibility. Other research is underway involving the transplantation of cells into the brains of patients, an approach that may eventually offer a cure.
ALD is an inherited disorder that leads to the loss of the myelin sheath, the fatty covering on nerve fibers in the brain. This leads to the gradual loss of all mental and physical function and usually death in several years. The problem is caused by a defect in the aptly named ALD gene, which makes a protein that is involved in breaking down specific fats called very long chain fatty acids. These fatty acids build up in the brain, destroying the myelin sheath.
ALD primarily affects males and can begin during adulthood or childhood between the ages of four and ten. The childhood onset form of the disease is typically more severe and boys afflicted with it usually die at a very young age.
"I think a great deal of progress has been made" in treating ALD, said Hugo Moser, who heads one of the few laboratories conducting research on the disease at Johns Hopkins University.
An effective treatment developed since the release of the film is bone marrow transplant, Moser told United Press International. But this is only effective in early stages of the disease and a suitable bone marrow donor is not always available. In advanced stages of the disease, there is very little that can be done.
It is critically important to diagnose the condition before symptoms develop because that is the best time to treat it, Moser said. "The capacity to diagnose the condition before symptoms appear is probably the greatest advance, but it isn't applied as widely as it should be," he said.
That is why Moser is attempting to make doctors aware of the need for families to get screened for the disease so treatment can be initiated before symptoms appear. The screening involves a simple blood test and can be done as early as the first few days of life, but unfortunately it is not a component of routine newborn tests and so the condition can often go undetected until it is too late.
Moser notes that because the disease has a genetic or hereditary component, extensive screening should be applied to any family member with a genetic relationship to somebody with the disease. This applies to cousins and other distant relatives and can sometimes require screening 100 family members or more.
"Since the illness runs in families, if we did these extended family screenings we could pick up 95 percent of patients," Moser said.
His team has screened several families and identified 500 people with the condition before they developed symptoms. More than 200 of them have undergone bone marrow transplants, he said. There are about 15,000 patients with the disease in the United States and 200,000 worldwide.
Some of these patients could be candidates for bone marrow transplants. But there are few options for others, and so researchers continue the search for treatments for the disease.
The movie touted Lorenzo's oil as a treatment that helped significantly improve Lorenzo and other patients afflicted with ALD. But the compound never panned out in clinical trials.
"The general conclusion is that the trials showed that it wasn't effective in patients who already had symptoms," Moser said. However, Moser's group recently completed a study looking at whether Lorenzo's oil could prevent the disease.
He is unable to discuss the results because they have not yet been published, but he said, "Depending on results of the study, Lorenzo's oil may have a place" as a preventative.
Lorenzo's father, Augusto Odone, who in a desperate attempt to save his son combed through medical books and journals and eventually stumbled on the promise of Lorenzo's oil despite the position of the medical establishment at the time that there was nothing that could halt the illness, holds out hope that the compound could work in adults and he still gives it to his son.
He concedes that Lorenzo's oil does not work in children under the age of 6 -- the population of boys used in clinical trials of the compound- but adds, "It is unknown if it would work in adults."
Lorenzo recently turned 24 and although severely disabled and unable to do much more than blink his eyes and wiggle his fingers, he has exceeded doctor's projections for his lifespan by 14 years so far. "The oil might have done something," Odone told UPI. "In fact, I think it has done something. But that's my personal view. It's not proven."
Other potential treatments for ALD have been examined over the years, including thalidomide and beta-interferon, which are used as treatments for multiple sclerosis, but these too proved ineffective, said Gerald Raymond, a neurologist and geneticist who works in Moser's lab.
"Since Lorenzo's oil, things have been both moving in good directions as well as disappointments," Raymond told UPI.
One agent that is giving researchers a lot of hope is phenylbutyrate. "This shows a lot of promise in the mouse," Raymond said.
Moser noted that he is "anxious to test (phenylbutyrate) in patients" and has applied for funding for the National Institutes of Health to conduct a trial to see if the compound is effective. He will know "in the next few weeks" if that trial will get approved.
"It's a little uncertain why it may work in ALD, but it may help stabilize a protein or it may turn on a gene related to ALD," Raymond said.
The Holy Grail would be a gene therapy that corrects the defective ALD gene, Raymond said.
This may come sooner than expected. "Gene therapy is being tested in animals and when it has gone through additional safety issues it will be tested in humans," Moser said.
In 1989, Odone founded the Washington, DC-based Myelin Project, which focuses on funding research to develop treatments for disorders caused by the loss of myelin in the brain, which includes multiple sclerosis along with ALD and other disorders.
The most promising treatment to come out of The Myelin Project is the transplantation of specialized cells called Schwann cells, which produce myelin in the brain. In experiments led by Timothy Vollmer at Yale, Schwann cells taken from a nerve in the ankle of three multiple sclerosis patients were transplanted into their brain in the hope that the cells will restore the myelin sheath and correct the damage done by the disease.
The small study was done only to determine if the procedure is safe so it will not offer an indication of whether the therapy is effective for treating the condition.
But scientists are very excited about the curative potential of the therapy because studies in animals showed that "these cells could not only restore myelin, they could also restore function," Lakshmi Bangalore, a spokesperson for Vollmer's research, told UPI.
If the therapy is effective for restoring myelin, it could treat any demyelinating disorder, including ALD.
In addition to the three MS patients who received the transplantation last summer researchers intend to treat two more patients with the therapy, Bangalore said.
Odone said early results should be ready in two to three months.
The MS patients will be followed for a year before there is any decision about moving forward with additional studies, and it could be another few years after that before the therapy is even considered for approval by the Food and Drug Administration for use in ALD patients, Bangalore said.
Although the therapy may hold the potential for curing ALD, it will be some time before it is ready for widespread use.
Odone noted that if the therapy is effective, he would use it on Lorenzo.
"It's a slim hope but it's better a long shot than no shot at all," he
© Copyright, 2002, United Press International