Conservative Iron Chelation as a Disease-modifying Strategy in Amyotrophic Lateral Sclerosis
Status:
Recruiting
Trial end date:
2023-11-01
Target enrollment:
Participant gender:
Summary
The alteration of iron metabolism is reported in animal models of amyotrophic lateral
sclerosis (ALS) as well as in sporadic and genetic forms (SOD1 and C9orf72) of ALS. The high
iron concentration of the brain, due to its high energy demand (high oxygen consumption),
makes motor neurons particularly vulnerable to energy deficit and oxidative stress.
Post-mortem examinations and MRI scans in patients with ALS have found signs of iron
accumulation in the central motor tract; and a high level of serum ferritin, which is a
marker of iron levels, is associated with a lower prognosis. In ALS mouse models, the use of
iron chelators has demonstrated neuroprotection and increased life expectancy, suggesting
that elimination of excess iron from the brain can prevent neuronal loss and, consequently, a
slow progression of the disease. Conservative chelation of iron refers to a modality whereby
much of the iron that binds to the chelator is redistributed in the body rather than
exhausted. Using a chelator, deferiprone, with this feature, in a safety pilot study, a very
good safety profile was observed. Deferiprone eliminated excess iron from brain regions,
reduced oxidative damage and cell death associated with regional iron deposits with no
apparent negative impact on the iron levels needed. Now, the efficacy of this new therapeutic
modality of neuroprotection is being evaluated in a randomized, double-blind,
placebo-controlled, multicenter study.