BRP - a new GLP1-like peptide
We dive into BRP, a possible new future for GLP1-like formulation that could be even more beneficial without the downsides.
GLP1 Receptor Agoinists are still the most well-researched type 2 diabetes and weight loss solutions that has been seen by modern science, but we like to keep an eye on what could be next.
Check out our quick explainer
Recently, there's been some news on BRINP2-related peptide ("BRP", colloquially), so we took a dive to learn more, starting with the article from MedicalXpress:
Krista Conger
Krista wrote the article here and the one at Stanford's main site (but we'll get to that later):
Krista Conger
What is BRP?
BRP is a peptide derived from the BRINP2 protein, corresponding to amino acids 386–397 (THRILRRLFNLC) of BRINP2.
This 12-amino acid peptide is flanked by KK and KR recognition sites within the BRINP2 protein, which are cleaved by proprotein convertases to release the peptide
While the above quote won't mean much to those who aren't professionally trained, the take-away is that similar to GLP1, BRP is a formulation that mimics a naturally occurring molecule – it's not a completely alien formulation that was manufactured.
More descriptive is the researcher's summary of the process of finding BRP:
Instead of manually isolating proteins and peptides from tissues and using techniques like mass spectrometry to identify hundreds of thousands of peptides, the researchers designed a computer algorithm they named Peptide Predictor to identify typical prohormone convertase cleavage sites in all 20,000 human protein-coding genes. They then focused on genes that encode proteins that are secreted outside the cell — a key characteristic of hormones — and that have four or more possible cleavage sites. Doing so narrowed down the search to 373 prohormones, a manageable number to screen for their biological effects.
[..]
As expected, the GLP-1 peptide had a robust effect on the neuronal cells, increasing their activity threefold over control cells. But a small peptide made up of just 12 amino acids bumped up the cells’ activity tenfold over controls. The researchers named this peptide BRP based on its parent prohormone, BPM/retinoic acid inducible neural specific 2, or BRINP2 (BRINP2-related-peptide).
One great thing about this development is that it suggests that this isn't the only molecule that might have similar effects to GLP1s – this might be the first of many.
What is the promise of BRP over GLP1s?
People care about BRP and the benefits it could bring because it is similar to GLP1s in all the right ways, but lacks the noted downsides – the effects on the gut and stomach.
While GLP1 was originally considered primarily a medicine intended to influence the gut (emphasizing "delayed gastric emptying"), scientists have come to realize that GLP1 is most effective as a brain drug – i.e. and excellent appetite suppressant and behavioral modifier.
BRP is promising because it can avoid the stomach/gut effects alltogether:
BRP primarily stimulates receptors in the hypothalamus and is consistent with GPCR activation leading to stimulation of CREB and Fos activity in neuronal cells.[1]
- Wikipedia
Who created BRP?
BRP was developed by a team at Stanford – and developed using Artificial Intelligence:
Krista Conger
There is a lot to be amazed about in how BRP was developed, but perhaps most interesting is that it's already showing efficacy in mice and pigs:
Notably, testing in animals also showed that it worked without some of the drug’s side effects such as nausea, constipation and significant loss of muscle mass.
It's a little disheartening to see the trope of "significant loss of muscle mass" being noted here, since that has been all but debunked/attributed to massive weight loss from GLP1s, but maybe they've seen some numbers we haven't.
Artificial intelligence's use was also called out in the article, where it was noted that they used it for finding the drug, not necessarily synthesizing it or dreaming up a chemical formulation as some might have hoped/expected.
How effective is BRP on humans?
This is a long way in the future. Breathless reporting on new methods and chemical formulations often have a way of distorting how close something might be, but we want to make this clear – BRP won't be in the hands of patients for a very long time.
As noted by the Stanford article:
Svensson has co-founded a company to launch clinical trials of the molecule in humans in the near future.
The start of the research, permitting and paperwork required to get this new formulation in the hands of humans (and see if it even still works) is only starting now, so it will be a multi-year (hopefully within a decade!) slog.
Likely by the time they make it to market, GLP1s will have long been out of patent protection (though there will undoubtedly be new, more effective GLP1s), but we welcome even more solutions to the obesity problem.
