What is Deferiprone and why is this drug of interest for Parkinson's?

Deferiprone is a drug already used to remove excess iron in the body in people who have certain blood disorders. Deferiprone is in a class of medications called iron chelators. The drug works by attaching itself to iron molecules in the body so excess iron can then be excreted. It is believed that excess iron in the part of the brain affected by Parkinson’s (the substantia nigra) may cause neuronal death (Forni et al., 2008). Deferiprone easily crosses the human brain's protective layer (the blood-brain barrier) crossing from the bloodstream into the brain, and in so doing it removes the excess iron which may be harmful to brain neurons.

Why do researchers think this drug is a potential treatment to slow, stop or reverse Parkinson’s?

It is believed that high levels of iron in the substantia nigra of people with Parkinson’s (PD) causes oxidative stress in neurons resulting in their demise. Oxidative stress can cause cell damage or death and is essentially an imbalance between the production of highly chemically reactive substances in cells and the ability of the body to counteract or detoxify their harmful effects. For many years, oxidative stress and mitochondrial dysfunction have been considered as one of the main mechanisms involved in cell death in PD and oxidative stress is exacerbated by free iron. Chelation (removal) of this free iron has powerful antioxidant effects known to dramatically increase cell survival, and it is hoped that decreasing the levels of iron in the brain will improve symptoms and decrease the rate of disease progression.

What will this trial investigate?

It is hoped that this trial will demonstrate for the first time in a large phase lll, multicentre, parallel-group, placebo-controlled, randomly selected trial that iron chelation with the drug Deferiprone will slow down the progression of the disease in PD patients. A nine month treatment period will be followed by a one month post-treatment monitoring period in order to assess the disease-modifying effect in the absence of deferiprone versus placebo. The Movement Disorders Society - Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) will be used which encompasses measurement of movement, cognition behaviour and activities of daily living.

What we envisage will happen after the trial?

We expect this trial to observe a significantly lower MDS-UPDRS score relative to the placebo controlled group. This will enable a demonstration of the efficiency of iron chelation as a treatment to slow the progression of the disease. It is hoped the trial will also show a positive impact on the quality of life. We hope that the findings of this new therapeutic concept will be widely disseminated in order to promote and support the clinical development of deferiprone and other selected iron chelators for the treatment of Parkinson’s.

At present, no neuroprotective drugs are available. If this trial demonstrates a disease-modifying effect, this new therapeutic strategy could be offered to people with Parkinson's.

Further Reading:

Details of the trial: https://clinicaltrials.gov/ct2/show/NCT02728843

To read more about the modes of action of deferiprone in Parkinson's: 'Drug Repurposing in Parkinson's Disease' ~ Dr Dilan Athauda and Professor Tom Foltynie