Obesity is a serious public health challenge worldwide, the present study is aimed to investigate the structural characteristic and anti-obesity effect of a water-soluble galactomannan (PEC) extracted from Eurotium cristatum (E. cristatum). Detailed analysis of the PEC structure showed a weight-average molecular weight of 32,305 Da and a composition of mainly mannose, galactose and small amounts of glucose. Nuclear magnetic resonance spectroscopy combined with methylation analysis indicated that the main chain of PEC is →5)-β-D-Galf-(1 → 6)-α-D-Manp-(1 → glycosidic bond, and the branched chain →2)-α-D-Manp-(1 → through →2,6)-α-D-Manp-(1 → is connected to the main chain by an O-2 bond. Furthermore, PEC was found to ameliorate body weight gain, metabolic disorders, and to modulate the gut microbiota in HFD-fed mice. Fecal microbiota transplantation trial confirmed that PEC prevented obesity development and metabolic disorders by reversing gut dysbiosis in HFD-fed mice. This is the first report of the isolation of PEC from E. cristatum, and the findings suggested that PEC exerted its antiobesity and related beneficial effects by regulating the gut microbiota. In conclusion, as a polysaccharide, PEC could reduce obesity by modulating the gut microbiota and has potential been a prophylactic agent for obesity and related metabolic diseases.

2024-11-01·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

In vitro fecal microbiota modulation properties of pectin and xyloglucan from hazelnut (Corylus avellana L.) skin, an industrial byproduct, and their incorporation into biscuit formula

Article

作者: Dertli, Enes ; Gonzales, Miguel Angel Alvarez ; Tunçil, Yunus E. ; Sarıoğlan, İhsan ; Tunçil, Yunus E ; Lindemann, Stephen R. ; Esen, Emine ; Arioglu-Tuncil, Seda ; Lindemann, Stephen R ; Alkay, Zuhal

The aim of this study was to extract water-soluble dietary fibers (WSDF_skin), pectin (PEC_skin), and xyloglucan (XG_skin) from hazelnut skin and to determine their impacts on colonic microbiota and metabolic function. WSDF_skin, PEC_skin, and XG_skin were extracted by water, acid, and alkali treatments, respectively. Monosaccharide analysis revealed WSDF_skin and PEC_skin were dominated by uronic acids, while the XG_skin was found to contain xyloglucan- and pectin-associated sugars. In vitro fecal fermentation analysis showed that WSDF_skin, PEC_skin, and XG_skin are fermented to different microbial short-chain fatty acid profiles by identical microbiota. 16S rRNA sequencing demonstrated that PEC_skin promoted Faecalibacterium prausnitzii and Lachnospiraceae related operational taxonomic units (OTUs), which are recognized as beneficial members of the human gut, whereas WSDF_skin and XG_skin stimulated Bacteroides OTUs. Interestingly, increased abundances of F. prausnitzii and Lachnospiraceae OTUs in PEC_skin were higher than those in commercially available pectin. Finally, PEC_skin and XG_skin were tested in a biscuit model and the results showed that either PEC_skin or XG_skin can be incorporated into biscuit formulations without impacting physical, textural, and sensory properties of the final product. Overall, our results demonstrated that hazelnut skin, an industrial byproduct, can be utilized for the production of functional dietary fibers, especially pectin, to improve colonic health.

2024-10-01·JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES

Pharmacokinetic and tissue distribution study of pectolinarigenin in rats using UPLC-MS/MS

Article

作者: Yang, Aixia ; Pan, Yingying ; Liu, Ping ; Chen, Lin-Lin ; Tan, Zihan

Pectolinarigenin (PEC), a natural flavonoid isolated from Cirsium japonicum, exhibits promising therapeutic potential for multiple cancers. In present study, a simple and sensitive UPLC-MS/MS method was established for the quantification of PEC in rat plasma and tissues. The assay procedure involved a one-step protein precipitation with tadalafil as the internal standard, and separation on a Welch Xtimate UHPLC C₁₈ column by gradient elution of acetonitrile/aqueous formic acid (0.1 %, v/v) at a flow rate of 0.2 m L·min^-1. The detection was conducted using multiple-reaction monitoring via an electrospray ionization source in positive ionization mode. The established method was proved to be highly sensitive with a good linearity (R² > 0.99) in respective concentration range (0.1-100 ng·mL^-1 in plasma and 1-10,000 ng·mL^-1 in tissues) and acceptable extraction recovery (≥71.17 %), matrix effect and stability, which was applied to study the pharmacokinetics and tissue distribution of PEC after intravenous (100 μg·kg^-1) and oral administration (10, 20 and 40 mg·kg^-1). PEC was promptly absorbed (T_max ≤ 0.222 h) and maintained at a low level with slow elimination (t_{1/2 z} ≥ 14.47 h) in rats after oral administration, resulting in extremely low bioavailability (0.56-0.68 %). However, PEC is widely distributed in rat tissues with high exposure in GI tract, liver and kidney. The bioavailability and tissue affinity were firstly revealed, which would guide directions for further development of PEC as an anti-tumor drug candidate.

项与 PEC Direct 相关的新闻（医药）

2024-02-15

·Business Wire

Poxel Reports Cash and Revenue for the Full Year 2023 and Provides Corporate Update

LYON, France--( BUSINESS WIRE )--Regulatory News: POXEL SA (Euronext: POXEL - FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare metabolic disorders, today announced its cash position and revenue and provided a corporate update for the twelve months ended December 31, 2023. Thomas Kuhn, Chief Executive Officer of Poxel , stated: “ We remain focused and continue to concentrate all our efforts at securing financing options, prioritizing non-dilutive solution, and partnerships. In particular, our relentless work as well as TWYMEEG ® ’s robust performance in Japan had led to the ongoing exclusive advanced discussions with a leading investor for monetizing royalties on TWYMEEG ® sales in Japan. We’ve also progressed our advanced discussions – in some cases on an exclusive basis – with several potential partners for each of our three proprietary products. Our goal is still to finalize one or more of these financing options and/or partnerships by the end of the first quarter of 2024 to start as soon as possible the next chapter of Poxel in rare metabolic diseases.” Commercial Update TWYMEEG ® (Imeglimin) For the quarter ended December 2023, TWYMEEG ® sales in Japan were of JPY 851 million (EUR 5.5 million) 1 as reported by Sumitomo Pharma. For its FY 2023, Sumitomo Pharma announced a forecast for TWYMEEG ® of JPY 4.2 billion 3 (EUR 26.9 million) 1 , which would represent a 90% increase over FY 2022 TWYMEEG ® gross sales. Based on this conservative assumption, Poxel expects to receive 8% royalties on TWYMEEG ® net sales. As part of the Merck Serono licensing agreement, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of TWYMEEG ® , independent of the level of sales. During Sumitomo Pharma’s FY 2024 (ending March 31, 2025), Poxel expects TWYMEEG ® net sales in Japan to reach JPY 5 billion (EUR 35.6 million) 1 entitling Poxel to receive 10% royalties on all TWYMEEG ® net sales and a sales-based payment of JPY 500 million (EUR 3.6 million) 1 . Beyond Sumitomo Pharma’s FY 2024, Poxel expects to receive escalating double-digit royalties as well as additional sales-based payments upon achievement of contractually based sales thresholds. For territories not covered by its agreement with Sumitomo Pharma, Poxel is still in advanced ongoing discussions with various potential partners for Imeglimin. Clinical, Manufacturing and Patent Update TWYMEEG ® (Imeglimin) Following the much higher increase in demand for TWYMEEG ® than expected, and temporarily tight inventories, Sumitomo Pharma continues to work diligently to increase production to ensure sustained inventory capacity. The Long-Term, 52-week, Open-label, Phase 4 Study conducted by Sumitomo Pharma of Imeglimin in Japanese Type 2 Diabetic Patients with Renal Impairment is currently ongoing in Japan to strengthen TWYMEEG ® profile in this key subpopulation. Top line results are expected in 2024. Rare metabolic diseases In February 2024, the European Patent Office (EPO) granted Poxel a new patent for PXL770, a novel, proprietary direct adenosine monophosphate kinase activator, which describes the use of PXL770 in the treatment of Autosomal-dominant polycystic kidney disease (ADPKD). This issued patent provides additional protection for PXL770 through 2041, with the potential for an additional 5 years through patent term extension. End of 2023, Poxel had been granted the same patent for PXL770 from the Japan Patent Office and the obtention is currently under review in other territories, including in the US. In adrenoleukodystrophy (ALD), PXL770 and PXL065 are prepared to advance, subject to additional financing, into two Phase 2a biomarker proof-of-concept (POC) clinical trials in male patients with adrenomyeloneuropathy (AMN), the most common ALD subtype. The studies will evaluate pharmacokinetics, safety and potential for efficacy, following 12-week treatment, based on relevant disease biomarkers, such as the effect on very long chain fatty acids (VLCFA), the characteristic plasma marker of the disease. Full-Year Cash and Revenue, ended December 31, 2023 Cash As of December 31, 2023, total cash and cash equivalents were EUR 2.3 million (USD 2.6 million) 1 , as compared to EUR 13.1 million (USD 14.0 million) as of December 31, 2022. EUR (in thousands) Q4 2023 Q4 2022 Cash 2,341 13,058 Cash equivalents - - Total cash and cash equivalents* 2,341 13,058 Unaudited data. *Net financial debt (excluding IFRS 16 impacts and derivative debts) was 45.1 million euros at the end of Q4 2023 as compared to EUR 29.5 million at the end of Q4 2022. With the priority objective of relaunching its R&D activities and executing its strategic plan in rare diseases, the Company has focused in recent months on securing additional financing, in particular non-dilutive solutions. In this context, the Company entered into exclusive negotiations with a leading investor to monetize royalties from TWYMEEG ® (Imeglimin) sales in Japan. In addition, the Company is in advanced discussions – in some cases on an exclusive basis – with several potential partners for each of its three products: Imeglimin, for several countries not covered by its agreement with Sumitomo Pharma, PXL065 and PXL770. Poxel’s goal is to finalize one or more of these financing options and/or partnerships by the end of the first quarter of 2024. Pending finalization of one or more of these agreements, and in a cautious approach given its limited financial visibility, the Company has completed a cost-saving plan in December, which includes a significant reduction in headcount, in order to adapt the Company's cost structure to its current operating needs. Key functions that enable the Company to finalize current transaction opportunities and continue its day-to-day operations have been retained, managing clinical, financial and business development activities. Based on: its cash position on December 31, 2023, the tranches already drawn 4 as of the date of this press release under the equity-linked financing facility with IRIS, no research and development expenses, and a strict control of operating expenses, Poxel expects that its resources, including funds available to it, will be sufficient to finance its operations and capital expenditure requirements until March 2024, by which time the Company expects to have completed one or more of its ongoing operations. Full-Year 2023 Revenue Poxel reported revenues of EUR 2.0 million for the year ended December 31, 2023, as compared to EUR 0.674 thousand during the corresponding period in 2022. Revenues for 2023 mostly reflects the JPY 313 million (EUR 2.0 million) of royalty revenue from Sumitomo Pharma, which represents 8% of TWYMEEG ® net sales in Japan. Based on its current forecast, Poxel expects to receive 8% royalties on TWYMEEG ® net sales in Japan through the Sumitomo Pharma fiscal year 2023 (April 2023 to March 2024). As part of the Merck Serono licensing agreement, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of Imeglimin, independent of the level of sales. EUR (in thousands) 2023 Q1 3 months 2023 Q2 3 months 2023 Q3 3 months 2023 Q4 3 months FY 2023 12 months FY 2022 12 months Sumitomo Pharma Agreement 449 506 664 362 1,981 673 Other - - - - - 1 Total revenues 449 506 664 362 1,981 674 Unaudited data Next Financial Press Release: 2023 Annual Results, on April 09, 2024 About Poxel SA Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology , including non-alcoholic steatohepatitis (NASH) and rare disorders. For the treatment of NASH, PXL065 (deuterium-stabilized R -pioglitazone) met its primary endpoint in a streamlined Phase 2 trial (DESTINY-1). In rare diseases, development of PXL770 , a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, is focused on the treatment of adrenoleukodystrophy (ALD) and autosomal dominant polycystic kidney disease (ADPKD). TWYMEEG ® (Imeglimin), Poxel’s first-in-class product that targets mitochondrial dysfunction, is marketed for the treatment of type 2 diabetes in Japan by Sumitomo Pharma and Poxel expects to receive royalties and sales-based payments. Poxel has a strategic partnership with Sumitomo Pharma for Imeglimin in Japan, China, and eleven other Asian countries. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan. For more information, please visit: www.poxelpharma.com All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. The Company does not endorse or is not otherwise responsible for the content of external hyperlinks referred to in this press release. Glossary You will find below a list of words and/or expressions that are used in this press release or in Poxel’s communication, with the aim to bring clarification and transparency: Sumitomo Pharma fiscal year runs April to March. As an example, Fiscal Year 2023 is April 1, 2023, through March 31, 2024. TWYMEEG ® royalties: As per the Sumitomo Pharma’s agreement, Poxel is entitled to receive royalties from the sales of TWYMEEG ® (Imeglimin) in Japan Sumitomo Pharma communicates gross sales of TWYMEEG ® , while TWYMEEG ® royalties are calculated on net sales. Net sales represent the amount of gross sales to which are deducted potential rebates, allowances, and costs such as prepaid freight, postage, shipping, customs duties and insurance charges. Poxel is entitled to receive escalating royalties of 8-18% on TWYMEEG ® net sales from Sumitomo Pharma. Positive net royalties : as part of the Merck Serono licensing agreement, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of TWYMEEG ® , independent of the level of sales. All royalties that Poxel receives from TWYMEEG ® net sales above that 8% level are considered as positive net royalties. Net royalties will therefore be positive for Poxel when TWYMEEG ® net sales exceed JPY 5 billion in a fiscal year and royalties reach 10% and above. 1 Converted at the exchange rate as of December 31, 2023. 2 Sumitomo Pharma fiscal year 2023 ends March 31, 2024. 3 As per Sumitomo Pharma FY2023 forecast of JPY 4.2 billion published on May 15, 2023. 4 Since March 31, 2023, 6 additional tranches have been drawn for a total amount of EUR 3.3 million.

引进/卖出财报临床2期临床3期

2023-11-27

·Science Daily

Stem cell-based treatment controls blood sugar in people with Type 1 diabetes

An innovative stem cell-based treatment for Type 1 diabetes can meaningfully regulate blood glucose levels and reduce dependence on daily insulin injections, according to new clinical trial results. The therapy aims to replace the insulin-producing beta cells that people with Type 1 diabetes lack. Dubbed VC-02, the small medical implant contains millions of lab-grown pancreatic islet cells, including beta cells, that originate from a line of pluripotent stem cells. An innovative stem cell-based treatment for Type 1 diabetes can meaningfully regulate blood glucose levels and reduce dependence on daily insulin injections, according to new clinical trial results from the University of British Columbia (UBC) and Vancouver Coastal Health (VCH). "This is a significant step toward a functional cure for Type 1 diabetes," said Dr. David Thompson, principal investigator at the Vancouver trial site, clinical professor of endocrinology at UBC and director of the Vancouver General Hospital Diabetes Centre. "For the first time, a stem cell-based device can reduce the amount of insulin required for some trial participants with Type 1 diabetes. With further refinement of this approach, it's only a matter of time until we have a therapy that can eliminate the need for daily insulin injections entirely." The findings, published today in Nature Biotechnology, arise from a multicenter clinical trial for an experimental cell therapy developed by U.S. biotechnology company ViaCyte (acquired by Vertex Pharmaceuticals) that is being clinically tested in Canada. The therapy aims to replace the insulin-producing beta cells that people with Type 1 diabetes lack. Dubbed VC-02, the small medical implant contains millions of lab-grown pancreatic islet cells, including beta cells, that originate from a line of pluripotent stem cells. The devices -- approximately the size of a Band-Aid and no thicker than a credit card -- are implanted just beneath a patient's skin where it is hoped they will provide a steady, long-term regulated supply of self-sustaining insulin. "Each device is like a miniature insulin-producing factory," said co-author Dr. Timothy Kieffer, a professor within the departments of surgery and cellular and physiological sciences at UBC, and past chief scientific officer of ViaCyte. "The pancreatic islet cells, grown from stem cells, are packaged into the device to essentially recreate the blood sugar-regulating functions of a healthy pancreas. This may have tremendous benefits over transplant of scarcely available donor-derived cells, given that we can create a virtually limitless supply." The clinical trial was conducted at Vancouver General Hospital, with additional sites in Belgium and the U.S. Ten participants, each of whom had no detectable insulin production at the start of the study, underwent surgery to receive up to 10 device implants each. Six months later, three participants showed significant markers of insulin production and maintained those levels throughout the remainder of the year-long study. These participants spent more time in an optimal blood glucose range and reduced their intake of externally administered insulin. One participant, in particular, showed remarkable improvement, with time spent in the target blood glucose range increasing from 55 to 85 per cent, and a 44-per-cent reduction in their daily insulin administration. The results are the latest in a series of clinical trials funded by Canada's Stem Cell Network and conducted by the UBC-VCH team. "The Stem Cell Network is delighted to support this clinical trial and we're pleased to see the promising results," said Cate Murray, president and CEO of the SCN. "Moving toward a functional cure for diabetes will require a coordinated and collaborative effort. It takes excellent science by top researchers in world-leading institutions, funders, like SCN, that de-risk research, and innovative biotech companies that can manufacture and scale the technology. SCN is proud to play its part and we look forward to what's next in game-changing diabetes research." The trials aim to accelerate the development and clinical testing of novel stem-cell based therapies for the 300,000 Canadians living with Type 1 diabetes. Diabetes is estimated to cost the Canadian health-care system $29 billion annually. Previously, in a 2021 study in Cell Stem Cell, the researchers were the first to show that the approach could produce insulin in the human body. The latest trial sought to significantly increase the amount of insulin produced by leveraging two-to-three times more devices per participant, alongside an updated device design with small perforations to allow for blood vessel ingrowth -- a feature aimed at improving survival of the lab-grown cells. In another ongoing trial, the UBC-VCH team is investigating whether a version of the device containing cells that have been genetically engineered to evade the immune system, using CRISPR gene-editing technology, could eliminate the need for participants to take immunosuppressant drugs alongside the treatment. "We envision a future where people with Type 1 diabetes are able to live their lives free from daily insulin injections and free from immune-suppressing drugs," said Dr. Thompson. "That future is now within reach, and Canada is leading the way in efforts to bring these novel treatments to patients."

临床研究临床结果细胞疗法

2023-08-16

·医药观澜

礼来、诺和诺德等数亿美元加码，首款产品刚获批！细胞疗法能否为糖尿病治疗带来新突破？

▎药明康德内容团队报道2023年6月底，糖尿病细胞疗法领域迎来一个重要里程碑进展：美国FDA宣布批准CellTrans公司的同种异体胰岛细胞疗法Lantidra上市，用于治疗1型糖尿病。公开资料显示，这是首款获批上市的1型糖尿病胰岛细胞疗法，代表着糖尿病治疗领域的新突破！糖尿病是威胁人类健康的主要慢性病之一。细胞疗法因具有从根源上治疗糖尿病的潜力，已成为行业关注的前沿方向之一。单是2023年以来，已有多家公司在糖尿病细胞疗法领域达成收购协议或合作，例如：6月30日，礼来（Eli Lilly and Company）宣布超3亿美元收购Sigilon公司，加码糖尿病封装细胞疗法；4月14日，诺和诺德（Novo Nordisk）宣布超6亿美元合作开发基于细胞的糖尿病生物打印组织疗法；3月29日，Vertex Pharmaceutical与CRISPR Therapeutics达成超3亿美元合作，助力糖尿病细胞疗法开发等等。那么，目前糖尿病治疗面临的挑战主要有哪些？细胞疗法有望解决糖尿病治疗中的哪些难题？当下，开发糖尿病细胞疗法面临的挑战又有哪些？图片来源：123RF———✦ 糖尿病何以难治？✦———糖尿病是由多种病因引起的代谢紊乱疾病。当人体不能有效地生产或使用胰岛素时，就会导致血糖水平升高，称为高血糖。在过去近100年的时间里，各种胰岛素和降糖新药相继涌现，极大改善了糖尿病患者的治疗格局。尽管如此，糖尿病领域仍然存在巨大未满足的治疗需求。根据国际糖尿病联盟（International Diabetes Federation，IDF）官网资料，2021年全球大约有5.37亿成年人患有糖尿病，相当于每10个成年人中就有1人患病。数据显示，在糖尿病患者中，超过90%的患者为2型糖尿病。这类患者的主要表现为对胰岛素产生抵抗现象，导致胰岛素的功能不能得到充分发挥。对于2型糖尿病患者而言，疾病管理的基石是保持健康的生活方式，血糖控制不佳时可辅以口服药物、联合治疗或者注射胰岛素。虽然目前已经上市的药物改善了很多患者的生活，但大多数无法解决2型糖尿病发生的根本原因——胰岛β细胞功能下降。糖尿病的另一种类型为1型糖尿病，这是一种慢性自身免疫性疾病，患者免疫系统攻击生成胰岛素的胰岛细胞，导致胰岛素缺失。患者需要接受终生护理，包括通过每日多次注射或使用泵持续输注胰岛素，同时还需要每天进行几次血糖检查，以指导其糖尿病的管理。有些患者在使用胰岛素时很难在预防高血糖的同时防止低血糖的发生。图片来源：123RF—✦ 细胞疗法：糖尿病患者的新希望 ✦—根据国际权威期刊Nature的介绍，细胞疗法是一种含有细胞的药物，通常被注射到患者体内。FDA将细胞免疫疗法、癌症疫苗和其它类型的自体和同种异体细胞均归入细胞治疗产品的范畴。近年来细胞疗法在研发中取得了许多关键突破。CAR-T疗法、现货型T细胞免疫疗法、造血干细胞疗法等不同类型的细胞疗法纷纷获批，为血液瘤、罕见病等治疗领域带来新选择。那么，细胞疗法能否为糖尿病患者治疗带来新突破呢？答案是肯定的。研究发现，在糖尿病的病理进程中，由于自身免疫或其它因素导致胰腺β细胞遭受破坏，不能生成足够的胰岛素来维持血糖的正常水平。因此，如果可以将健康的胰腺细胞或能生成胰岛素的胰岛细胞移植到糖尿病患者体内，就有可能实现胰岛素的供应和血糖水平的调节。相较传统的降糖药物，糖尿病细胞疗法有望大幅降低用药频次，提高患者生活质量和治疗便利性，甚至有望为患者带来“一次治疗、永久获益”的潜在治愈希望。2023年6月，首款同种异体胰岛细胞疗法Lantidra获得FDA批准，用于治疗1型糖尿病。该产品由CellTrans公司开发，主要作用机制被认为是通过输注的同种异体胰岛β细胞并产生足够的胰岛素，使得患者不再需要接受胰岛素注射来控制其血糖水平。在两项非随机单臂研究中，共有30例1型糖尿病患者接受了至少一次、最多三次输注。结果显示，21名受试者不需要服用胰岛素一年或更长时间，其中11名受试者不需要胰岛素1-5年，10名受试者不需要胰岛素5年以上。除了已获批的Lantidra，目前全球还有多款糖尿病细胞疗法正在临床开发中。例如：Vertex公司在研干细胞来源的同种异体胰岛细胞疗法VX-880，正在开展治疗1型糖尿病的1/2期试验；Creative Medical Technology开发的同种异体细胞疗法CELZ-201，正在开展治疗1型糖尿病的1/2期试验；Vertex Pharmaceuticals与CRISPR Therapeutics联合开发的干细胞分化胰岛细胞疗法VCTX210，已完成治疗1型糖尿病的1期试验；ViaCyte公司（已被Vertex公司收购）在研干细胞来源的胰岛细胞替代疗法PEC Direct（VC-02），正在开展治疗1型糖尿病的1/2期试验等。这意味着，细胞疗法将有望惠及到更多的糖尿病患者。图片来源：123RF———✦挑战和机遇并存✦———作为一种新型治疗手段，糖尿病细胞疗法总体尚处于产业化早期阶段，因此也面临诸多挑战。其中，最大的挑战之一是如何降低或者避免移植排斥反应，因为注射到人体的新细胞可能会被患者自身免疫系统判定为外来物质而被攻击。例如上文提及的Lantidra、VX-880和VC-02等产品，患者在注射细胞产品后需要接受免疫抑制治疗，以保护胰岛细胞免受免疫排斥。另外，糖尿病细胞疗法的开发还有其它问题有待解决，比如：如何提高植入细胞的长期存活率、如何保持有效的胰岛素分泌功能、如何在不影响其它机能的情况下实现胰岛素的适宜分泌、如何扩大细胞的生产、如何提高患者可及性等。当下，研究人员正在尝试通过生物工程、基因编辑和免疫调控等技术解决上述难题。例如，胰岛细胞疗法VCTX210利用了CRISPR Therapeutics公司的基因编辑技术，可生成能够逃避免疫系统识别的胰腺细胞。再如，围产期组织衍生细胞（PRDC）疗法CELZ-201利用通用供体细胞的分泌因子来重新编程患者自身的免疫细胞，使得该产品具有PRDC的可自我更新、低抗原性和低毒性的特点，并能在临床上进行大规模扩增。此外，使用封装技术来保护细胞免受免疫系统攻击也是一个重要研发方向。此前，诺和诺德（Novo Nordisk）与康奈尔大学（Cornell University）已经在合作开发封装设备方面取得突破，该封装设备将保护移植入患者的β细胞免受免疫系统的攻击。今年4月，诺和诺德又与Aspect Biosystems就开发糖尿病生物打印组织治疗产品建立合作，后者的平台技术使得开发一种具有生物功能和免疫保护性包装并基于细胞的疗法成为可能。期待糖尿病细胞疗法领域能够取得更多的进展和突破，为患者带来更多的治疗选择！参考资料：（可上下滑动查看） [1]FDA Approves First Cellular Therapy to Treat Patients with Type 1 Diabetes. Retrieved June 28, 2023, from https://www.prnewswire.com/news-releases/fda-approves-first-cellular-therapy-to-treat-patients-with-type-1-diabetes-301866374.html[2]Lilly to Acquire Sigilon Therapeutics. Retrieved June 29, 2023, from https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-sigilon-therapeutics[3]Vertex and CRISPR Therapeutics Announce Licensing Agreement to Accelerate Development of Vertex’s Hypoimmune Cell Therapies for the Treatment of Type 1 Diabetes. Retrieved March 28, 2023, from https://www.businesswire.com/news/home/20230324005339/en[4]Aspect Biosystems and Novo Nordisk enter partnership to develop bioprinted tissue therapeutics for diabetes and obesity，Retrieved April 13th, 2023 from https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=166089[5]Cellular & Gene Therapy Products. From https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products[6]Cell therapies articles from across Nature Portfolio. From https://www.nature.com/subjects/cell-therapies#:~:text=A%20cell%20therapy%20is%20a%20medicinal%20product%20containing,stem%20cell%20transplantation%29%20and%20mesenchymal%20stem%20cell%20therapies.[7]About diabetes. From https://idf.org/about-diabetes/introduction/本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

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