P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease

Today's cyclodextrin, ,

Today’s cyclodextrin: After a long time, HPBCD will be evaluated again in clinics, now in a new application.
ZyVersa Therapeutics Inc. is sponsoring this Phase 2a open-label, two- to three-center study to evaluate the clinical efficacy and safety of one dose level of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) given intravenously in adult patients with type 2 diabetes, diabetic kidney disease (DKD), and proteinuria.

According to the proposed mechanism of action, HPBCD entraps and passively removes intracellular cholesterol from the kidney. It is also believed to promote active cholesterol removal through up-regulation of cholesterol efflux transporters ABCA1 and ABCG1.

Study Details | P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease | ClinicalTrials.gov


Methods for the treatment of chronic kidney disease

drug development, , ,

We are happy to announce the acceptance of a great patent from CarboHyde’s collaborator, Renatus, a pharmaceutical company focused on developing cyclodextrin-based cholesterol metabolism modulators. Renatus is a pharmaceutical company whose mission is to provide safe and effective treatment options for the treatment of numerous cholesterol-driven diseases such as chronic kidney disease, atherosclerosis, and Alzheimer’s diseases. The core technology of the company allows the normalization of cholesterol homeostasis by removal of excessive and toxic cholesterol within diseased cells without significant harmful effects on normal cells.

The lead asset RN-005 is a cholesterol metabolism modulator that has proven strong therapeutic efficacy in preclinical models of both diabetic kidney disease (DKD) and focal segmental glomerulosclerosis (FSGS) wherein dysregulated cholesterol metabolism causes progressive damage and loss of function in the kidney. The gamma-cyclodextrin oligomers are effective in cholesterol metabolism enhancement, cholesterol efflux, reducing inflammatory cytokine secretion, renal clearance of cholesterol, and/or reducing albuminuria. Therefore, the gamma-cyclodextrin oligomers can be used to treat or alleviate chronic kidney disease, symptoms thereof and/or complications related to chronic kidney disease.

Espacenet – METHODS FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE

Oral alpha-cyclodextrin reverses cholesterol-crystal-induced retinal pathology in a rodent model of type 2 diabetes

Today's cyclodextrin, ,

Today’s cyclodextrin a study showing how alpha-CD treatment could be used in type-2 diabetes patients.
Cholesterol crystals were eliminated from the retinas of diabetic mice after oral alpha-cyclodextrin treatment. These findings demonstrate that T2D is associated with cholesterol crystal-induced retinal pathology that is improved using oral alpha-cyclodextrin. Improvements were observed in inflammation, neural function and visual response.

Oral alpha-cyclodextrin reverses cholesterol-crystal-induced retinal pathology in a rodent model of type 2 diabetes (T2D). | IOVS | ARVO Journals

Described are methods for using cyclodextrin to treat, inhibit, prevent, ameliorate, or cure diabetes

carbohydrates

We have seen many applications for using cyclodextrin as active ingredients, yet diabetes has not been on the list yet.
Until now.
Alessia Fornoni and Merscher Sandra shared a concept for reducing lipid content in a cell or plasma membrane of a cell in a patient suffering from diabetes to redistribute or reduce cellular cholesterol accumulation.

US20230338412 METHOD OF USING CYCLODEXTRIN (wipo.int)

Cyclodextrin Host–Guest Recognition in Glucose-Monitoring Sensors

Today's cyclodextrin

today’s cyclodextrin: is about glucose sensors from Abolfazl Heydari et al.
Monitoring blood glucose levels is crucial in diabetes management, aiding in clinical decision making and reducing the incidence of hypoglycemic episodes, thereby decreasing morbidity and mortality rates. Despite advancements in glucose monitoring (GM), the development of noninvasive, rapid, accurate, sensitive, selective, and stable systems for continuous monitoring remains a challenge.

In this concept, cyclodextrins (CDs) can be instrumental in the development of GM systems due to their high supramolecular recognition capabilities based on the host–guest interaction. The introduction of CDs into GM systems not only impacts the sensitivity, selectivity, and detection limit of the monitoring process but also improves biocompatibility and stability. We can categorize CD-based sensors into four groups based on their modification strategies, including CD-modified boronic acid, CD-modified mediators, CD-modified nanoparticles, and CD-modified functionalized polymers. These findings shed light on the potential of CD-based sensors as a promising tool for continuous GM in diabetes mellitus management.

Cyclodextrin Host–Guest Recognition in Glucose-Monitoring Sensors | ACS Omega

An Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice

carbohydrates, drug delivery

Glucose-responsive insulin-delivery platforms sensitive to dynamic glucose concentration fluctuations and providing both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. RMIT University and Monash University present biodegradable and charge-switchable phytoglycogen nanoparticles capable of glucose-stimulated insulin release. The nanoparticles are “nanosugars” bearing glucose-sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (≈95% loading capacity) to form nano complexes. A single subcutaneous injection of nano complexes shows a rapid and efficient response to a glucose challenge in two distinct diabetic mouse models, this results in optimal blood glucose levels for up to 13 h. The nano complexes’ morphology is key to controlling rapid and extended glucose-regulated insulin delivery in vivo. These studies reveal that the injected nano complexes enabled efficient insulin release in the mouse, with optimal bioavailability, pharmacokinetics, and safety profiles. These results highlight a promising strategy for the development of a glucose-responsive insulin delivery system based on natural and biodegradable nano sugar.
Rong XU, Sukhvir Kaur Bhangu, Karly Sourris, Domitilla Vanni, Marc-Antoine Sani, Karen Alt, Be’eri Niego, Dr. Quinn A. Besford, Brendan Dyett, Irena (Iśka) Carmichael, Mark Cooper, Christoph Hagemeyer, Francesca Cavalieri, et al

See the full article here: An Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice

ZyVersa Therapeutics and Larkspur health acquisition corp. announce business combination, interim financing, and pipe investment update

drug development, , , ,

A little business for today:
ZyVersa Therapeutics Inc., a clinical-stage specialty biopharmaceutical company developing, among others, a cyclodextrin drug candidate (VAR 200), announced an aggregate committed financing in support of the business combination at $10.0 million.
This investment will enable Zyversa to advance clinical evaluation of the cholesterol efflux mediator candidate (VAR 200) in patients with orphan renal disease, FSGS, and to progress into Phase 1 trials – said Steve Glover and Daniel J. O’Connor
Read more on the ZyVersa website