A Feasibility and Safety Study of Afamelanotide in Acute Stroke Patients – An Open Label, Proof of Concept, Phase Iia Clinical Trial

Abstract

BACKGROUND Neuroprotective agents have the potential to improve the outcomes of revascularisation therapies in acute ischemic stroke patients (AIS) and in those unable to receive revascularisation. Afamelanotide, a synthetic α-melanocyte stimulating hormone analogue, is a potential novel neuroprotective agent. We set out to assess the feasibility and safety of afamelanotide for the first time in AIS patients. METHODS AIS patients within 24 hours of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled. Afamelanotide 16 mg implants were administered subcutaneously on Day 0 (D0, day of recruitment), D1 and repeated on D7 and D8, if not well recovered. Treatment emergent adverse events (TEAEs) and neurological assessments were recorded regularly up to D42. Magnetic resonance imaging (MRI) with FLAIR sequences were also performed on D3 and D9. RESULTS Six patients (5 women, median age 81, median NIHSS 6) were recruited. Two patients received 4 doses and four patients received 2. One patient (who received 2 doses), suffered a fatal recurrent stroke on D9 due to a known complete acute internal carotid artery occlusion, assessed as unrelated to the study drug. There were no other local or major systemic TEAEs recorded. In all surviving patients, the median NIHSS improved from 6 to 2 on D7. The median Tmax volume on D0 was 23 mL which was reduced to a FLAIR volume of 10 mL on D3 and 4 mL on D9. CONCLUSIONS Afamelanotide was well tolerated and safe in our small sample of AIS patients. It also appears to be associated with good recovery and radiological improvement of salvageable tissue which needs to be tested in randomized studies. ClinicalTrials.gov Identifier: NCT04962503

New insights underlying the early events of dopaminergic dysfunction in Parkinson’s Disease

“…Our results strongly suggest a central role for 𝝰-MSH at the onset of dopaminergic dysfunction in PD. Since 𝝰-MSH is implicated in more than one symptom of prodromal PD such as constipation [107,108], restless leg syndrome [109,110], sleep disorders [111][112][113] and excess sebum production "oily skin" [114,115], 𝝰-MSH levels may serve as an early biomarker for disease onset and progression. Providing answers to this and other questions raised by our findings will help to produce a clearer understanding of PD pathophysiology.…”