Lorenzo’s Oil Could Not Cure Lorenzo, But Newborn Screening Is Expected To Save Others From His Fate
By: Rita Rubin
Lorenzo’s Oil, a 1992 film starring Nick Nolte and Susan Sarandon, depicted Augusto and Michaela Odone’s quest for a treatment that could save their son Lorenzo from dying of a rare genetic disorder.
Since the film’s release, Lorenzo Odone, his parents and Dr. Hugo Moser, the physician-scientist whose help the Odones sought, have all died. But a new piece of their legacy promises to help improve the lives of boys who inherited the same genetic disease that struck down Lorenzo.
Health and Human Services Secretary Sylvia Burwell last month recommended that every state begin screening newborns for the disorder. Newborn screening means that other boys who inherited the condition will be identified and treated before they develop symptoms–at which point it is too late to stop their killer.
Lorenzo was an exceptionally bright 6-year-old when his behavior changed, his movements became awkward and his parents noticed something was wrong with his hearing. Doctors diagnosed him with X-linked adrenoleukodystrophy, or ALD, passed from mother to son on the X chromosome (women carriers usually don’t get sick because they also have a normal copy of the gene on their other X chromosome, although some develop neurological symptoms in middle age). ALD affects an estimated 1 in 20,000 males.
ALD results in the buildup of very long chain fatty acids in the nervous system, adrenal gland and testicles. The accumulation of fatty acids strips nerves of myelin, their protective sheath. In boys whose symptoms appear in childhood, ALD eventually leads to severe disability, coma and death.
Although neither of the Odones had trained as a scientist–he was a World Bank economist, she a linguist–they created the first treatment for their son’s condition: an oil that combined two fats extracted from olive and rapeseed oils. The point of the oil is to flood the bodies of boys who inherited the ALD gene with relatively harmless fats to stop them from making the very long chain fatty acids.
Unfortunately, the treatment came too late to save the young man for whom it was named. Lorenzo died in 2008, a day after his 30th birthday.Researchers found that Lorenzo’s oil can stave off symptoms only in boys who, although they inherited the ALD gene, still appear to be normal. (Even so, Augusto Odone, who died at age 80 in 2013, and Michaela Odone, who died of lung cancer at age 61 in 2000, believed that the oil had stabilized their son, enabling him to live years longer than doctors had predicted, albeit in a vegetative state.)
The problem is that most parents of boys with asymptomatic ALD are, as the Odones were, blissfully ignorant of the devastating disease lying in wait for their sons. In every state except one, boys who appear to be normal don’t undergo genetic testing for ALD unless they have a brother or cousin who’s developed symptoms and been diagnosed with the disease. Boys who have no such relatives, or those whose relatives won the genetic coin toss and didn’t inherit ALD, aren’t diagnosed until symptoms appear.
That is about to change. With Burwell’s blessing, ALD is the latest of five conditions that have been added to the Recommended Uniform Screening Panel, or RUSP, since the original panel was approved in 2008. The RUSP is designed to guide states’ newborn screening programs, and most at least screen for the recommended conditions.
The HHS Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children meets regularly to consider adding conditions nominated by parent advocates, organizations and experts.
“Disorders on the RUSP are chosen based on evidence that supports the potential net benefit of screening, the ability of states to screen for the disorder, and the availability of effective treatments,” according to the advisory committee’s website. Data presented to the committee suggested that if funding is available, states should be able to begin screening for ALD in one to three years.
Even before ALD was added to the RUSP, New York state decided it was worthwhile to screen newborns for the disorder. Since state began screening for ALD in December 2013, 17 confirmed or probable cases have been identified in boys, while 19 girls have been confirmed as being carriers, according to the New York Department of Health.
In addition, California, New Jersey and Connecticut have already passed laws supporting the launch of newborn screening for ALD once the HHS secretary recommended it.
Burwell’s endorsement of newborn screening is somewhat bittersweet for Ann Moser, the widow of Dr. Hugo Moser, who developed the first blood test to diagnose ALD. Until his death in 2007 at age 82, Hugo Moser directed the Neurogenetics Research Center at Baltimore’s Kennedy Krieger Institute, an internationally recognized center for the treatment and study of developmental disabilities and disorders of the brain, spinal cord and musculoskeletal system in children and young adults. In 2013, Kennedy Krieger opened the Moser Center for Leukodystrophies in his honor.
“It was my late husband who saw the need for ALD newborn screening,” Moser, a research associate in neurology at Kennedy Krieger, told me in a recent interview. “It was nearly 10 years ago that he started talking about it and advocating for it and putting it on the list of disorders that should be screened in the newborn period.”
Hugo Moser served as the basis for the character of Dr. Gus Nikolais, played by Peter Ustinov, in Lorenzo’s Oil. At one point in the film, Nikolais tells the Odones, “I will have nothing to do with this oil.” In an interview years ago, Augusto Odone told me that “the movie was a little bit unfair to him…Dr. Moser always kept his mind open.” Indeed, in a 1993 review of Lorenzo’s Oil in The Lancet, a British medical journal, Moser criticized the film for inventing conflicts between the Odones and the medical establishment (although he did note that Ustinov, “except that he wears a bow tie, has copied my appearance and speech with remarkable accuracy”).
Ann Moser has spent much of the time since her husband’s death working on an inexpensive screening test for ALD that could use dried blood from the heel stick all newborns receive. A pilot study in which nearly 5,000 Maryland newborns were screened for ALD proved that it was feasible.
“It was his dream that it be included in the newborn screening panel nationally,” Moser said of her husband. “He would have been very, very pleased, because so many boys will be saved.”
Untreated, roughly a third of all boys who inherited ALD will develop the severe childhood form of the disease and, on average, they die about three years after the symptoms first appear, said Dr. Ali Fatemi, who directs the Moser Center for Leukodystrophies at Kennedy Krieger. (The majority of the rest of the sons who inherit the ALD gene don’t develop symptoms until they are young adults, and they generally progress more slowly.)
But if boys with the ALD gene are identified before symptoms appear, they can begin taking Lorenzo’s oil and receiving MRI scans twice a year to watch for changes in their brain. If pre-symptomatic changes are seen on MRI scans, a bone marrow transplant can arrest the progression of the disease.
Lorenzo’s oil is still an experimental treatment, and 50 to 60 people are currently taking it, said Dr. Gerald Raymond, who, after Moser’s death, directed the Neurogenetics Research Center at Kennedy Krieger for three years before moving to the University of Minnesota. Raymond oversees the “expanded access program“ for Lorenzo’s oil, through which boys 18 months to 18 years of age can get the treatment.
“I think our demand is only going to increase with newborn screening,”said Raymond, adding that he was “ecstatic” that ALD had cleared the RUSP hurdle.