Results of Experiment to Test Integrity of Blood-Brain Barrier
Last month, the SDBC reported that it was conducting an experiment in collaboration with UCSD radiology department to test the integrity of the Blood-Brain-Barrier in transgenic mice (Tg). The experiment, which involved four Tg mice (age: 2 months) and four non-Tg mice (age: 2 months), was conducted by Dr. David Vera. Mice were treated with the same concentration of radiolabeled polysaccharide for the same length of time, followed by PET imaging of their brains. The results obtained showed that the
Blood-Brain-Barrier is intact in transgenic mice used in the experiment. This experiment will be repeated when the transgenic mice are 9–12 months old.
Some of you may be wondering about the significance of these studies. It has been speculated by some scientists that the reason why the SDBC’s SMARTTM Molecules (SMs) cross the Blood-Brain-Barrier is that the Blood-Brain-Barrier may be damaged / compromised in transgenic mice. Although we don’t know the mechanism for the migration of SMs into the central nervous system, SDBC scientists don’t think that the Blood-Brain-Barrier is compromised because without the intact Blood-Brain-Barrier, the interior milieu of the central nervous system (CNS) of transgenic mice (and patients) would be flooded by humoral (of or relating to the body fluids, esp. with regard to immune responses involving antibodies in body fluids as distinct from cells ) neurotransmitters and blood elements that would cause serious injury to the CNS, resulting even in death. Therefore, it is important for us to establish the integrity of the Blood-Brain-Barrier beyond the shadow of a doubt. By screening the two month old transgenic mice we have established the base line. We will monitor these mice as they age.
Expression of alpha-synuclein in Transgenic Mice – We previously reported that the SDBC is developing alpha-synuclein transgenic mice. Before using these mice in our experiments we need to determine the level of alpha-synuclein expression (production) in their brains. These studies are underway. We have already established which of the pups have inherited the alpha-synuclein gene. The levels of protein expression need to be determined.
PET Imaging of Alpha-Syn Mice – Contractual arrangements are being made with Centre D’ Imagerie Moleculaire De Sherbrooke and USC for PET imaging experiments with alpha-synuclein mice. The goal of this study is to determine whether or not misfolded alpha-synuclein can be detected in substantia nigra (SN) in a mouse brain. SN is a very small organ which may be very difficult to visualize in a small brain such as that of a mouse.
Mutant-LRRK2 Project – The SDBC has intensified its effort to raise funds to buy 20 mg of mutant LRRK2 protein, which will cost in excess of $200K. The Company is eager to develop an antagonist to inhibit the activity of mutant LRRK2 kinase because this activity is responsible for the production of excessive phosphorylated LRRK2 protein implicated in Parkinson’s disease.