It seems that squalamine does not cross the blood brain barrier. Making it ‘safer’ for the experimentally minded. However it dose have good bioavailbility so it will have effects everywhere except the brain.
http://europepmc.org/articles/PMC1062159
"Squalamine is somewhat unique among most current anti-angiogenic agents in development because it inhibits endothelial cell proliferation and migration induced by a wide variety of growth factors, including Basic Fibroblast Growth Factor (bFGF) and VEGF (27,31; Fig. 2). This broad antiangiogenic activity of squalamine may result from its inhibition of surface sodium–proton exchangers (thus altering intracellular pH and thereby impeding intracellular signaling by several growth factors) and other downstream signaling pathways in endothelial cells"
I would not touch the stuff.
Peter
Dear Peter, all,
Just for your information, this squalamine study is investigating a new road for the pathogenesis of PD, the so called “gut-brain” hypothesis.
Unfortunately, we don’t yet know the causes of PD, but In the clinician world in the past 20 years there was suggested the idea that PD may generate at first from some dysregulation of the Enteric Nervous System (ENS) (in the guts), that would only afterwards reflect on the Central Nervous System (CNS) and manifest PD.
This was supported by evidence that a protein that seems strongly related to PD, called a-Synuclein, is found dysregulated also in the neurons of the guts and this happens sometimes prior to clinical diagnosis.
This study that Dr Zasloff is carrying out right now is therefore aimed to deliver the compound to the nerves of the guts (and hence not directly entering the brain; as Peter was suggesting Squalamine does not pass the blood brain barrier, or it does in only small amounts) and evaluate if this in return would normalise the neuronal function of the brain.
It is still difficult for scientists/doctors to design effective drugs for PD, not knowing the exact mechanisms of this very complex disease, but hopefully this study will be a first step in this direction.
Remaining at disposal,
Michele
I find the title of your paper misleading
since you refer to squalamine as a “natural substance” that inhibits the formation of a-Synuclein is not able to reach the site where the offender forms.