Recently, University College London Hospitals (UCLH) received a “Specials License” to allow the treatment of six patients suffering from Creutzfeldt–Jakob Disease (CJD), by way of a novel antibody known as PRN100. The results of this treatment have now been published in The Lancet.
There is currently no cure for CJD, yet over 100 people per year develop it either spontaneously or through external means including (but not limited to) growth hormones, cataract surgery or infected neurosurgical implements [1]. “There is no UK legislation which implements a compassionate use programme as set out in Article 83 of the relevant EU regulation. But the UK has implemented an exemption process known as the “Specials” in light of the requirement to be able to deal with special needs.” [2]
As there is no known cure, the request for use of PRN100 was put before the court as in Law “Some treatment decisions are so serious that the court has to make them.”
Permission was granted for PRN100 to be offered to six patients. One of the ways in which treatment via a specials license differs from that in a clinical trial, is that any procedures performed on the patient must exclusively be for their clinical needs. This means any blood samples or brain scans were be routine and required whether the therapy was happening or not. Because of this, the safety and efficacy of PRN100 can only be determined through examination of these routine tests.
CJD is caused by the (often post-translational) misfolding of the PrPC protein from its default α-helix rich form into a β-sheet pathological variant. Once the β-sheet structure in place, this works as a scaffold to sequester other normal prions and misfold them into the pathological variant. As an antibody, PRN100 works by selectively and specifically binding to the normal prion protein. This binding then prevents or interferes with refolding into the pathological form.
“Although disease progression was not halted or reversed in any patient, MRC Prion Disease Rating Scale scores did appear to stabilise in three patients for periods when cerebro-spinal flud drug concentrations reached the target concentration, but the small number of patients precluded meaningful statistical analysis.”[3] That being said however, PRN100 was able to successfully cross the blood-brain barrier and reach target concentrations. Whilst there, no clinically significant reactions (side-effects) to the treatment were seen. CJD is an extremely rapid disease, often with a duration of only six months. As there were no significant reactions, this leaves hope that PRN100 might be a potential treatment should it be applied earlier in the disease. The paper discusses “Based on these safety data and demonstration of brain accessibility to PRN100 following intravenous administration, a larger study, ideally at the earliest possible intervention, is now warranted.”
[1] https://www.thelancet.com/article/S1474-4422(22)00082-5/fulltext
[2] https://www.bailii.org/ew/cases/EWCOP/2018/29.html
[3] https://www.thelancet.com/article/S1474-4422(22)00082-5/fulltext
