PRION DISEASES AND PRN100
CJD is a degenerative brain disorder caused by misfolded prion proteins, which destroy brain cells. The disease is rapidly progressive and leads to death usually within 1 year of onset of illness and often much sooner. Currently, CJD is responsible for 1 in 5000 deaths in the UK.
The Difficulty in Developing a Treatment
The MRC Prion Unit at UCL has conducted long-term research to investigate potential antibody treatments for prion disease and to see if such treatments might work and what side effects or other safety issues might be anticipated. The immune system recognises foreign proteins and other parts of germs as being alien to the body and this leads to the body producing specific antibodies tailored to fight that infection. However, since prions are formed from one of the body’s own proteins they are not recognised in the same way by the immune system and lifesaving antibodies are not produced. This is one of the reasons why prions are so lethal.
The team at the MRC Prion Unit at UCL have developed a pioneering treatment, PRN100.
How PRN100 Might Work
PRN100 is an antibody specifically designed to bind tightly to the normal prion protein with the aim of preventing it from combining with the prions and in this way stop a chain reaction and formation of new prions.
PRN100 and related antibodies have potent activity in binding to prion protein and preventing prion disease in laboratory models.
The Challenges Ahead
Laboratory tests have provided a “proof of principle” that PRN100 works by preventing the chain reaction and the formation of new prions, but there are still many challenges for patient treatment.
Despite these unknowns, given the lack of any alternative treatment for a disease that is rapidly and invariably fatal, the research team at the MRC Prion Unit at UCL, patients, relatives and colleagues at University College London Hospitals (UCLH) agree that PRN100 should be offered to patients with rapidly progressing CJD at this time.
The UCLH Trust has given approval to do this and a small number of patients are being treated.
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Patient Treatment Challenges
There are a number of uncertainties in the use of PRN100 treatment.
For example, will sufficient PRN100 get from the blood into the brain where it needs to work, by crossing the blood-brain-barrier (a natural mechanism protecting the brain) when given intravenously (into a vein in the arm)?
Will it need to be given directly into the fluid (cerebrospinal fluid) around the brain? Will there be immediate or long-term side effects of a severity that limits an effective dose being given?