What is PAL, or PEG-PAL or Pegvaliase or Palynziq?

If you have been looking into PKU treatments, you might have heard one of the names above at some point and wondered ‘what exactly is that?’ PAL, PegPal, Pegvaliase and Palynziq all refer to different aspects of a single method of treatment for PKU. This is an enzyme replacement therapy which is usually injected.

As a brief reminder, enzymes break down the amino acids in protein. People with PKU cannot produce enough of the enzyme Phenylalanine Hydroxylase (PAH) to break down all the amino acid called phenylalanine (phe). Phenylalanine is common in many foods, which is why we have to eat a restricted diet.

PAL: the enzyme

PAL stands for Phenylalanine Ammonia Lyase, which is a common enzyme in many plant species. The name is similar to PAH because both of them break down phe. Basically, PAL does in plants what PAH does in humans. But PAL breaks the amino acid down differently. Fortunately, the process results in two end products which are easily processed by humans. This is why it has been developed as a treatment for people who can’t produce enough PAL — those of us with PKU.

PEG-PAL: the stealth enzyme

The addition of PEG in front of PAL in this term indicates that the enzyme PAL has been mixed with Polyethylene glycol, or PEG. This is a compound which is safe for humans to consume and is commonly used in medicine. In this case, the PEG is used to disguise the PAL enzyme from the immune system.

Remember that PAL is an enzyme found in plants, so it is foreign to the human body. If it were injected without PEG then the immune system would see the enzyme as a threat and destroy it. So PEG-PAL is basically the enzyme in stealth mode, able to hide from the immune system and get to work.

Pegvaliase and Palynziq: brand names

BioMarin has developed PEG-PAL into an injectable treatment for PKU. Initially, this was called ‘Pegvaliase’ but it is now called ‘Palynziq’. Essentially, they are brand names for the treatment PEG-PAL; in the same way that Panadol is a brand name for paracetamol. It is worth noting that BioMarin is the same company which developed Kuvan — the pills which can improve phe absorption in some people with PKU.

Does it work?

Palynziq is now used widely in the US. While it works in theory and in many patients, life is complicated. As noted above, PAL is a plant enzyme which is foreign to the human body. Even with the stealth coating offered by PEG, it still causes problems during treatment. It has side effects similar to those experienced when the human immune system fights a foreign chemical.

BioMarin notes some of these concerns as joint pain, headache, skin reactions that spread and last at least 14 days (such as itching, rash, or redness), itching, nausea, stomach pain, mouth and throat pain, vomiting, cough, diarrhoea.

What next? The UK is excluded

In May 2019, the European Commission gave permission to BioMarin to market Palynziq in Europe for PKU patients who are aged 16 and older, and who have blood phe levels greater than 600 micro mol/L despite being on diet.

The UK is no longer in the EU, so a separate licence is needed to offer Palynziq here. BioMarin have stated that they will not be pursuing a licence to provide Palynziq in the UK. (Another Brexit benefit?)