Daily doses of lithium, a drug used to treat bipolar disorder, have been found to delay progression of amyotrophic lateral sclerosis (ALS) in an Italian study of 44 people with the disease.
No other treatment to date has shown such a dramatic effect on this paralyzing and fatal disease of adults, which affects some 30,000 Americans.
Francesco Fornai at the University of Pisa (Italy), with colleagues at the University of Novara (Italy) and the Santa Lucia Foundation in Rome, announced their results online today in Proceedings of the National Academy of Sciences.
At the end of a 15-month trial that began in October 2005, about 30 percent of the patients that took riluzole, a drug known to have modest benefit in ALS, had died, while all those receiving riluzole plus lithium had survived. The disease progressed markedly in the riluzole-only group but progressed very slowly in the riluzole-plus-lithium group.
“Although the number of study participants is small, the results are very intriguing,” said Dr. Valerie Cwik, MDA medical director and vice president of Research. “MDA has already had conversations with researchers in the United States to follow up on these results with a larger, confirmatory study.”
Sixteen trial participants were randomly selected to receive 50 milligrams a day of riluzole plus two daily doses of 150 milligrams of lithium carbonate. (If necessary, doses were adjusted up to 450 milligrams a day during the study to maintain targeted blood levels.)
The remaining 28 participants were randomly assigned to receive riluzole only.
The two groups were carefully matched with respect to the number of patients with bulbar ALS, the most rapidly progressive form, and pulmonary function.
A parallel study in mice with a genetic form of ALS suggested that lithium works by increasing autophagy, a process in which worn-out or abnormal cellular components are destroyed, and boosting the number of mitochondria, the energy-producing units of cells.
Lithium must be taken under a doctor’s supervision and with frequent monitoring of blood levels. Early signs of lithium toxicity include diarrhea, vomiting, drowsiness, weakness and lack of coordination. Later signs include giddiness, blurred vision, ringing in the ears and a large output of dilute urine.