Fairbanks Pharmaceuticals awarded a Phase 1 SBIR grant for $192,101 by NIDDK/NIH

Dr. Alan Schneyer, CEO/CSO and Co-founder of Fairbanks Pharmaceuticals, is the Principal Investigator (PI) of an SBIR grant from The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at The National Institutes of Health (NIH). The award begins immediately and funds our research that will identify a number of candidate compounds using our proprietary screening bioassay, comparing them for biochemical and biological properties, and testing the top candidates for biological activity in islet culture assays.

The award lasts for a one year period. It is anticipated that the successful completion of this Phase 1 award will lead to a larger Phase 2 award, which will allow testing the biological activity of lead compounds in animals. The goal of Fairbanks Pharmaceuticals, and this SBIR grant, is to develop compounds that lead to regeneration of insulin-producing beta cells to replace those lost to either type 1 or type 2 diabetes and thereby partially or completely eliminate diabetes in these patients. Stay tuned for progress reports….

Increased transdifferentiation of alpha to beta cells in FSTL3 knockout mice

Fairbanks scientists collaborated with UMass-Amherst faculty to determine whether the increase in insulin-producing beta cells observed numerous times in FSTL3 knockout mice results, at least in part, from enhancing alpha to beta cell transdifferentiation. A process called “lineage tracing” in which alpha cells are permanently marked with a yellow tag was used to monitor their fate over time. Alpha cells typically produce glucagon, a hormone that counteracts insulin and helps prevent glucose from falling too much. Yellow cells that now produce insulin (a hallmark of beta cells) were identified in wild type mice and the number of these cells was increased significantly in mice in which the FSTL3 gene was inactivated (FSTL3 Knockout mice) that have elevated activin signaling.

These results support our hypothesis that activin and related growth factors enhance alpha to beta cell transdifferentiation resulting in increased numbers of functional beta cells.

These results were published in the journal Endocrinology in March 2016 (Endocrinology 157: 1043–1054, 2016). View in Pubmed

Activin regulates alpha and beta cell fate-determining gene expression

The transcription factor Arx is required to form pancreatic islet alpha cells while the factor Pax4 is required to specify beta cells.  Reducing Arx expression in alpha cells is sufficient to turn them into beta cells.Fairbanks scientists have collaborated on  new research published in Endocrinology showing that activin directly suppressed Arx and increased Pax4 expression, consistent with our hypothesis that increased activin signaling promotes alpha to beta cell transdifferentiation.

Since FSTL3 knockout mice have increased activin signaling, these new results suggest that the enhanced beta cell formation in FSTL3 knockout mice could be due to activin-assisted transdifferentiation from alpha cells.  More research is needed to determine if this process occurs naturally and amenable to intervention as a basis for developing novel diabetes treatments.

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Activin restores insulin release in diabetes

Fairbanks Pharmaceuticals scientists collaborated on a recently published study in which the hormone activin was applied to human islets from donors who had type 2 diabetes.  In untreated islets, glucose failed to stimulate insulin secretion as one would expect in diabetes.  But in the activin treated islets, elevated glucose stimulated insulin release to levels seen in normal islets in the absence of activin.

This is important because of another part of this study in which gene expression was compared between normal and diabetic islets.  Activin production is very high in normal islets but reduced by 50% in diabetic islets.  Critically, the activin inhibitor, FSTL3, is expressed at 8-fold greater levels in diabetic islets compared to normal.  This means that functional activin (activin not inhibited by FSTL3) is much lower in diabetic islets.  This suggests that one defect in diabetic islets is loss of activin signaling and when that activin is restored, insulin release returns to normal.

Fairbanks Pharmaceuticals is developing technology that will inhibit the action of FSTL3. Therefore, the newly published research suggests that this technology could have important therapeutic effects in patients with diabetes to enhance insulin release and restore more normal glucose control.

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Fairbanks Pharmaceuticals Awarded MLSC Intern

Fairbanks Pharmaceuticals received an award from the Massachusetts Life Science Center to hire an intern starting in July 2015. Eddie MesitiAlfredo (Eddie) Mesiti, a 2014 graduate from the University of Massachusetts-Amherst with an undergraduate degree in Microbiology, was selected to fill this role.

Eddie is currently completing a Masters Degree in Applied Molecular Biotechnology.  This internship will help him in his degree program while amplifying progress in pursuing our research agenda.  Welcome Aboard Eddie!

Fairbanks Pharmaceuticals opens research laboratory

On November 25th, 2014, Fairbanks Pharmaceuticals opened its research laboratory in Springfield, Massachusetts.

Alan and Danielle 2
Technician Danielle Andrzejewski and CEO/CSO Alan Schneyer

The space is located at 3601 Main St within recently renovated open lab space that has a wealth of shared facilities available to Fairbanks scientists.

In our first two weeks we have been screening libraries to identify candidate compounds that we can then test for effectiveness in treating diabetes in animal models.  Its been a hectic start but now we are ready to focus on our research and hopefully make excellent progress.

The science behind Fairbanks Pharmaceuticals

In order to determine the function of Follistatin Like-3 we created knockout mice in which the gene that codes for this protein was disabled.  Mice without FSTL3 had larger pancreatic islets and improved glucose control suggesting that loss of FSTL3 might be beneficial for patients with diabetes.  We continued our analysis of these mice and found that the increased number of insulin producing beta cells was not due to increased proliferation of the existing beta cell population.

Our current research is focused on whether loss of FSTL3  stimulates a process where other cell types in the pancreas, such as alpha cells, change their fate and become beta cells, a process known as transdifferentiation or reprogramming.  Regardless of the actual mechanism, however, Fairbanks Pharmaceuticals is focused on development of new diabetes therapies based on altering FSTL3 function.