SLC20A2

The intricate dance of nature often unfolds in mysterious ways, hidden from the naked eye. At the heart of this enigmatic tango lies a vital partnership: the symbiosis between plants and a type of fungi known as arbuscular mycorrhizal (AM) fungi. New groundbreaking research delves into this partnership, revealing key insights that deepen our understanding of plant-AM fungi interactions and could lead to advances in sustainable agriculture. The intricate dance of nature often unfolds in mysterious ways, hidden from the naked eye. At the heart of this enigmatic tango lies a vital partnership: the symbiosis between plants and a type of fungi known as arbuscular mycorrhizal (AM) fungi. New groundbreaking research, recently published in the journal Science, delves into this partnership, revealing key insights that deepen our understanding of plant-AM fungi interactions and could lead to advances in sustainable agriculture. AM fungi live within plant root cells, forming a unique alliance with their plant hosts. This relationship is more than a simple coexistence; it involves a complex and critical exchange of nutrients essential for fungal survival and highly beneficial for the plant. Researchers at the Boyce Thompson Institute (BTI) have uncovered the roles of two proteins, CKL1 and CKL2, which are active only in the root cells containing the AM fungi. These two proteins belong to a larger family of proteins known as CKLs, whose functions in the plant have yet to be fully understood. "The closest relatives of the CKL family are proteins, called CDKs, that control the plant cell cycle and are located in the nucleus of the cell. Surprisingly, the CKL1 and CKL2 proteins have evolved a different role than CDKs -- they do not control the cell cycle. They are tethered to the membranes of the root cell, including a membrane that surrounds the fungus," said Dr. Sergey Ivanov, a post-doctoral researcher at BTI and first author of the study. The scientists found that these CKL proteins are critical for the fungi's survival within plant roots. They play a pivotal role in controlling the flow of lipids (fats) from the plant to the fungi, a process essential for the fungi's nourishment. Without these proteins, key genes that manage this lipid transfer are not activated, starving the fungi. The research also uncovered a complex web of interactions involving several receptor kinase proteins. One of these kinases is known for its role in allowing the AM fungus to penetrate the root's outer layer. The researchers discovered that this same kinase adopts a new role deeper within the root, where it partners with CKL proteins, potentially to initiate the flow of lipids to the fungus. Surprisingly, while CKL proteins are vital for controlling lipid flow, they don't manage the entire symbiotic lipid pathway. Instead, they control genes responsible for the start and end of this pathway. Meanwhile, a key protein operating in the middle of this pathway, RAM2, is activated by a different regulator, RAM1. For full-scale lipid production to occur, both the CKL and RAM1 pathways must be active. "Lipids are costly for the plant, so dual regulatory mechanisms may ensure that lipid provisioning is tightly controlled, perhaps a safeguard against exploitation by fungal pathogens," said Dr. Maria Harrison, a professor at BTI and senior author of the study. Harrison continued, "In an agricultural context, leveraging this natural symbiosis could lead to crops that are more efficient in nutrient uptake and more resilient to environmental stressors." This study not only deepens our understanding of the molecular dynamics behind plant-AM fungal symbiosis but also highlights the intricate and often unseen connections that sustain life on our planet. It's a reminder of the incredible complexity and interdependence found in nature, much of it hidden right beneath our feet. Funding for this research was provided by the US National Science Foundation Plant Genome Research Program.

SHANGHAI, Dec. 13, 2023 /PRNewswire/ -- Alebund Pharmaceuticals ("Alebund" or the "Company"), an integrated biopharmaceutical company focusing on developing innovative therapies for the treatment of renal diseases and related chronic conditions, announced phase II proof-of-concept study results for the investigational drug, AP306, a first-in-class, pan-inhibitor of sodium-dependent phosphate transporters, which was discovered by Chugai Pharmaceutical Co., Ltd., and previously referred by EOS789. In this phase II study (NCT05764590), patients on maintenance hemodialysis with hyperphosphatemia (n=55) were 1:1 randomized to AP306 or sevelamer carbonate after a washout period. Patients on AP306 followed a dose titration schedule from 75mg TID to 150mg TID per protocol during the 12-week treatment. Patients on sevelamer carbonate followed dose titration from 800mg TID per its package insert. The primary endpoint was the change in serum phosphorus from baseline to end of treatment. At the end of treatment, the effect size of serum phosphorus reduction from baseline for AP306 was clinically significant; and the response rate (defined as serum phosphorus lower than 5.5 mg/dL) in AP306 treatment arm was much higher in comparison to that in sevelamer carbonate arm. AP306 was well tolerated with no unexpected safety findings observed. Detailed results from this phase II study will be presented at an upcoming medical conference. Dr. Sharon Moe, from the Indiana University School of Medicine, an internationally recognized researcher and key opinion leader for chronic kidney disease-mineral and bone disorder (CKD-MBD), will chair the steering committee of AP306 program, working closely with Alebund to continue its clinical development. Dr. Moe has been principal investigators for several ongoing basic and clinical research studies in the field of CKD-MBD and was the leading investigator for AP306 (EOS789) phase 1b study. "Hyperphosphatemia remains a significant clinical problem in patients undergoing dialysis but with suboptimal control despite widespread use of phosphate binders. Treatment of AP306, a pan-inhibitor of PiT1 and PiT2 in addition to NaPi2b, achieved a higher serum phosphorus reduction with a lower pill burden than phosphate binder. Encouraged by the data from this proof-of-concept study, AP306 is promising for substantially improving phosphate control in dialysis patients with hyperphosphatemia." said Dr. Jin Tian, Co-founder and CMO of Alebund. "We are delighted to see the phase II data of AP306," Dr. Gavin Xia, Co-founder, Chairman and CEO of Alebund commented, "These results strengthen our confidence that AP306 could be a novel treatment for patients with hyperphosphatemia as a single agent. With AP301 (phase III ongoing) and AP306, we have a global leading hyperphosphatemia portfolio, which will address the huge unmet needs for hyperphosphatemia management." About Hyperphosphatemia Hyperphosphatemia is one of the most common complications in CKD patients. The long-term elevated serum phosphorus level could cause multiple complications such as secondary hyperparathyroidism, renal osteodystrophy and vascular calcification. It is an independent risk factor of cardiovascular events and all-cause mortalities. A good control of serum phosphorus level could effectively improve the patients' outcome. For CKD patients undergoing dialysis treatment, the regular dialysis is not sufficient to remove the overload of serum phosphate in the body. Considering the limitations of low-phosphate diet which might cause dystrophia, oral use of phosphate binders is the prevailing treatment for hyperphosphatemia. However, less than 50% can maintain reaching a good phosphate control with current treatment options. About the study NCT05764590 is a phase II randomized, open-label, active-controlled, multicenter study to evaluate the safety and serum phosphorus lowering effect of AP306 in chronic kidney disease patients receiving maintenance hemodialysis with hyperphosphatemia. The primary efficacy endpoint measures the change in serum phosphorus level from the baseline to the end of 12-week treatment or before the initiation of rescue therapy. Participants enrolled in the study were randomized in a 1:1 ratio to be treated with either AP306 or sevelamer carbonate. The study involved 11 investigational sites in China, led by Dr. Li Wang from Sichuan Provincial People's Hospital. About Alebund Pharmaceuticals Alebund is a biopharmaceutical company jointly incubated by a group of industry leaders in the field of nephrology in Shanghai in 2018. Alebund focuses on the discovery and development of novel therapies primarily for kidney diseases and their complications, as well as other chronic conditions. Alebund has built a diversified and balanced pipeline of drug candidates targeting a range of renal diseases, including chronic kidney disease (CKD)/dialysis complications, IgA nephropathy, diabetic kidney disease, and autosomal dominant polycystic kidney disease (ADPKD). Alebund's pipeline comprises both small-molecule and biological assets, in which the most advanced program is undergoing a pivotal phase III study. About AP306 AP306 (EOS789) is an oral inhibitor of phosphate transporters, NaPi-IIb, PiT-1, PiT-2, which was discovered by Chugai Pharmaceutical Co., Ltd.. Under the option and license agreement between Alebund and Chugai in 2021, Alebund conducted the phase II study with data reported in this release. Alebund has fully executed the global rights option and now owns the global development and commercialization rights for AP306. SOURCE Alebund Pharmaceuticals