Additional GDF11 information that may be of interest:
Changing The Licensing, Manufacturing Paradigms Within The Regulatory Framework
Dr. Allen says Harvard was originally planning on licensing its GDF11-associated assets to distinct companies that would engage separate and specific neurodegenerative, musculoskeletal, metabolic, and cardiovascular diseases, following the standard, “siloed” approach most often seen in academic/biotech partnerships. In keeping with his “let’s address aging, rather than its disease-specific symptoms” philosophy, he convinced the team to change that paradigm from the outset. “All of the work that we do on manufacturing and safety is synergistic to multiple different applications of the molecule,” he explains. “Of course, we still have to go through the same regulatory processes for each individual disease we treat, because there’s no regulatory process for aging. If there were, it would take years to develop, akin to AFAR’s TAME trial to study the impact of treating aging by preventing the rate of age-related disease onset – a six-year study requiring 3,000 patients. That ends up being a super long study with thousands of patients because to prevent diseases, you need to wait until the onset of the diseases, which could take years for each patient.”
Instead of initially targeting disease prevention, Dr. Allen and company spent the bulk of its first three years exploring which of dozens of potential age-related diseases might offer the fastest path to market. “Our North star, ultimately, is to get to market with a therapy that prevents multiple age-related diseases,” says Dr. Allen, but he realizes that’s not a pragmatic approach given the regulatory structure. “To move toward that goal, we identified the most devastating age-related diseases that we could treat for the shortest possible duration to see clinically meaningful effects in an unmet need where there’s no good alternative treatment,” he says.
The vascular system was the obvious answer. “The most prominent effects of GDF11 happen in the vasculature, where we see improvement in a very short duration of treatment,” says Dr. Allen. Put simply, the protein regenerates blood vessels. “In our group, Lee Rubin has focused on the effects of the protein in the vasculature of the brain. The vasculature of the brain deteriorates with age. When scientists stain and image brain vasculature, it resembles a large spider’s web in a young brain, but only a few chicken scratches in the elderly brain. When we introduce GDF11 in old animals, their brains look young again, with a higher quantity of vasculature, improved blood flow, and decreased inflammation.” The result, he says, is an increase in nutrient delivery, more efficient expulsion of waste, and release of trophic and healing factors. “When we look at diseases and related trauma having to do with the vasculature, such as heart attack and stroke, we see significant improvement in recovery of cardiac and brain function resulting from the introduction of GDF11.”
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GDF11 protein found to inactivate triple-negative breast cancer cells
Researchers detail a possible way to re-engage a tumour suppressor protein, that has been found to be inactivated in triple-negative breast cancer cells…
On the strength of these preclinical results, Elevian is gearing up to enter human clinical trials with GDF11 for the treatment of stroke.
“We really got the green light to go into humans based upon the animal data that we got there,” Allen said, adding that there is still a lot of work to be done before they reach this phase. “We still have to scale up production of the drug and we have to do extensive safety and toxicology tests – IND-enabling studies. The longest pole in the tent is figuring out how to make manufacturing costs effective. The cost of goods is going to be really, really high. So we’re doing a lot of work in process development right now, and then we’re going to hand it off to a manufacturing partner to scale up. We’re about two years from initiating our human clinical trial in stroke.”
Another unmet need where Elevian believes GDF11 can have an impact is Type 2 diabetes, a disorder whose pathology is also intricately connected to the circulatory system – and often to aging.
Along with blood clotting factors, glucose resides within the inside lining of blood vessels. In Type 2 diabetics, the lining of an individual’s blood vessels begins to become glycosylated, which causes them to narrow, impeding blood flow. Glucose tolerance is known to decrease with age.
In a study published in March 2020, Wagers and her colleagues stated that GDF11 was shown to “significantly improve glucose tolerance in aged mice” and increase glucose homeostasis, under a variety of dietary conditions.
Some negative stories - the first in the MIT tech review magazine:
As a general rule, mouse models are usually pretty bad predictors of efficacy because they typically don’t accurately represent the disease. This is especially true when using a progeroid mouse model. We know that progeria isn’t true age acceleration - so this is probably not a very meaningful failure.
