Seems the field of Alzheimer’s disease research and the field of neurosciences got hit by a storm a couple of days, with the press release of Biogen Idec about some very promising success in early clinical trials for Alzheimer’s disease, this especially comes a few months after Roche dropped their clinical trials due to inconclusive clinical efficacy.
Why it is big news? It simply because when you deal with neurological disorders you have to deal to big bottleneck: the blood-brain barrier (BBB). To give you a context, the BBB allows less than 5% of current FDA-approved drugs to cross it and this is for small molecules. However, you need bigger cargos to deliver to target neurological diseases (like antibodies, enzymes or growth factors) and we easily talk about 20-100X bigger size compounds. We already try to squeeze hard a mouse across a hole in the BBB, think about try to smuggle an elephant.
It seems there is an Alzheimer’s/Parkinson’s disease international conference taking place in Nice, France. Biogen Idec is one company specialized in drug delivery targeting the central nervous system. Right now, one way to try to cross the elephant across the BBB is to identify some receptors that can be used in a Trojan Horse to deliver the elephant across the BBB.
They found a particular antibody (aducanumab) capable to recognize a receptor and deliver its cargo across the BBB. Yet, they don’t stipulate which receptor it is the target. Is is the transferrin receptor that everyone try on (because it is highly enriched at the BBB) or the same receptor that binds Angiopep-2, the flagship BBB-selective peptide develop by Biogen-Idec? We will have to wait on that (until the paper got published)
One way to assess that you successfully deliver your elephant is to see how the elephant behave inside the brain. And the preliminary data look fairly promising as noted by the reduction of plaques in Alzheimer’s patients but also a slowing of the cognitive decline observed in these patients.
There are still a lot of issues to be taken care of, in particular edema (brain swelling) and immunogenicity (your immune system recognize the antibody as foreign agent and develop a immune response to it), but more importantly into a larger scale of patients (did they get a lucky set of patients or is it representative on the average population)?
We’ll see how things go because nothing is yet winned but in the war against neurodegenerative disorders, any small victories are highly celebrated among the high number of defeats. The good news is that the FDA opened a fast-track for the clinical trials, in other means it tries to open a HOV lane to help push the approval and get a new drug on the market in 3-4 years compared to the 5-10 years it usually takes.