http://www.nutraingredients-usa.com/Publications/Food-Beverage-Nutrition/NutraIngredients/Research/Broccoli-can-reverse-diabetic-heart-damage-say-researchers/?c=rhc%2BPi6aUoEN3UqRG1jcwA%3D%3D

“Our study suggests that compounds such as Sulforaphane from broccoli may help counter processes linked to the development of vascular disease in diabetes,” said Thornalley.

Diabetes

Published online August 4, 2008, as db06-1003

"Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease"

Authors: Mingzhan Xue, Qingwen Qian, Adaikalakoteswari Antonysunil, Naila Rabbani, Roya Babaei-Jadidi, and Paul J. Thornalley

“In heart failure, you lose cardiomyocytes, so the only way to reverse heart failure is to make more of these cells.” Said William Pu, the study’s lead researcher and a paediatric cardiologist at the Children’s Hospital in Boston, Massachusetts. The new findings come on the heels of two earlier break throughs.

In 2006, scientists identified another cardiac stem cell – marked by the expression of a gene called Nkx2-5 – with  the potential to become lining blood muscle or cells lining blood vessels in the organ’s left-sided chambers.

Key role of stem cells

Gene expression is the process by which information encoded in the DNA of a particular gene is transformed into a protein or RNA, which plays a key role in protein synthesis.  In parallel, other U.S. researchers discovered a related progenitor heart cell – so-called because of its capacity to generate different types of tissue – that produces the same cell types in the right sided heart chambers.

Mr.Pu’s study, published online in the journal Nature, shows for the first time that new heart stem cells can also be derived from a third type of cardiac stem cell, located within the surface of the organ and identifiable through its expression of a gene called Wtl.

The results were independently verified by another team of scientists at the University of California in San Diego, whose research was published in the same issue of Nature.  Mr.pu and his colleagues showed that the cells from the heart’s outer lining, called the epicardium, can not only metamorphose into cardiomyocytes but also into smooth muscle cells, endothelial cells, which line the interior of blood vessels, and fibroblasts, found in connective tissue.

http://medicalscienceandtechnology.blogspot.com

The Pervasis technology has actually been around for over 10 years. Vascugel was originally licensed by Reprogenesis where Dr. Helen Nugent (a co-founder of Pervasis) started her biotech career. The technology didn't make it when Reprogenesis merged with Creative Biomolecules and Ontogeny to form Curis, and judging from Dr. Nugent's affiliations on publications, she went back to MIT (at least for awhile) to further develop this technology in Edelman's lab. Pervasis was formed in 2003 and they have emerged as a company focused on this single vascular health technology. The team has enhanced and optimized the technology over the last several years and journal articles can be found at the Pervasis web site that describe the science.

Their most recent publication gives a glimpse into their manufacturing strategy. This includes:

1. growing up sufficient ECs in flasks,
2. seeding these cells onto Gelfoam (pig collagen) scaffolds, and then
3. growing the ECs on the Gelfoam until the the ECs grow to a certain density within the scaffolds (see above graphic).

The manufacturing process in the manuscript seems a little complex and the quality control (QC) assays too extensive. First, the EC/collagen constructs are periodically analyzed for cell counts to determine when the constructs are 'ready', meaning they need to sacrifice product for testing. Not ideal. It would be nice to be able to qualify a process where some non-invasive method (alamar blue, oxygen consumption) could be used to establish EC confluence with the sponges. Secondly, they test for several biological activities that they argue are potential mechanisms for why the ECs work. While this makes nice science, it complicates the QC strategy. It is really best to just focus on one or two, to make sure that you are not tied in to all 5 assays as release criteria upon BLA. Why pay for 5 expensive assays when one will get you to where you need to go at 20% of the costs? They also culture in the presence of serum (as most cell therapy companies do), and it will be interesting to understand how they wash or rinse their product prior to human use. The other question is around the stability of the product. Are they cryopreserving the cells in the Gelfoam (not in publications), or is Vascugel a fresh product that has a finite (days to weeks) shelf-life once harvested? These are very important issues to address, as the FDA expects you to have a locked down process and strategy once you start Phase III trials, which they might not be too far away from.

Pervasis should be getting initial data from their closed Phase II trials this year. According to the trial design found at clinicaltrials.gov, it looks like they have a 6 month endpoint with 2.5 years of extended follow-up. Assuming positive results (and that my time-frame assumptions are correct), this would allow them to justify initiation of a Phase III trial in 2009. Things to track in the next year will be 1) what new indications they test clinically, 2) if they can get the injectable Vascugel product working as good at the Gelfoam-based product, and 3) if they can initiate a trial based on the injectable product technology.