Tailored to fit: China optimizes policies and regulations regarding drug registration and review to promote innovation in traditional Chinese medicine.

The classification system for drug registration and the review and approval process influence the innovation and development of pharmaceuticals. China's previous classification standards for registration of traditional Chinese medicines (TCMs) overly emphasized the material basis while neglecting the clinical value of TCM. Moreover, the review and approval system did not fully consider the characteristics of new TCM drugs, such as the clinical experience already available for many TCM formulations guided by TCM theories. This resulted in suboptimal quality and quantity in the development of new TCM drugs. Since 2019, China has introduced a series of policies and regulations aimed at reforming the classification system for registration of TCMs and establishing a review system tailored to TCM characteristics. The new classification system for registration of TCMs emphasizes that the development of new TCM drugs should be oriented towards clinical value, focusing on meeting unmet clinical needs. The policies and regulations promote the conversion of prescriptions in ancient classics into new drugs and encourages the conversion of preparations from medical facilities into new TCM drugs. Secondary development of already marketed TCM products is encouraged to enhance the advantages of their clinical use. The new review system places importance on the role of TCM theories and clinical experience in supporting the registration of new TCM drugs. These reform measures have paved a path for registration and review of the characteristics of TCMs and will positively promote the development of new TCMs.

Involvement of adaptive immune responses in a model of subacute colitis induced with dextran sulfate sodium in C57BL/6 mice.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disorder. Pharmacotherapy serves as the main treatment strategy for IBD; however, the current medications have certain limitations, such as inefficacy and a tendency to induce tolerance, thereby requiring the development of innovative drugs to fulfill therapeutic requirements. A model of acute colitis induced with a solution of approx. 3% dextran sulfate sodium (DSS) has been widely used in preclinical drug development. Nevertheless, this model has some drawbacks, including rapid disease progression leading to mortality in some mice and disparities between the inflammatory characteristics of mice and the pathological features of human IBD. The current study found that mice freely consuming a lower concentration of a DSS solution (1-1.5%) for 10-15 days exhibited milder colitis symptoms. Continued consumption of the DSS solution for 15-20 days resulted in chronic inflammation in colon tissue, accompanied by a significant increase in the proportion of Th1 cells, indicating the involvement of adaptive immune responses. Subsequently, mice were treated with mesalazine or Centella triterpenes while concurrently consuming the DSS solution for 10 days. The treated mice had significant improvements in body weight and colon length compared to the control group. The advantages of this subacute model include minimal mortality among experimental mice and the fact that intestinal mucosal inflammation in mice resembles the pathological features of human IBD, enabling the assessment of drug efficacy against IBD.

Development of amyloid beta-directed antibodies against Alzheimer's disease: Twists and turns.

Alzheimer's disease (AD) is a severe and progressive neurodegenerative disease, and the treatment options that are currently available are limited. The amyloid cascade hypothesis has had a significant influence in explaining the pathology underlying AD. Inhibiting the production and aggregation of amyloid-beta (Aß) and promoting its clearance have been important strategies in the development of anti-AD drugs over the past two decades. Specifically, Aß directed antibodies have been highly anticipated, but drug development has been fraught with obstacles and challenges. Antibodies targeting the C-terminal or central region of Aß, such as ponezumab, solanezumab, and crenezumab, primarily bind to Aß monomers, yet no significant clearance of brain plaques or slowing of disease progression has been observed in clinical trials. Antibodies targeting the N-terminal region of Aß, including aducanumab, lecanemab, and donanemab, primarily bind to aggregated forms of Aß, and have shown efficacy in clearing brain plaques and slowing early-stage AD progression in clinical trials. However, clinical trials of gantenerumab, which targets conformational epitopes in the N-terminal and central sequences of Aß and which selectively binds to aggregated forms, have failed, raising some new questions about the Aß hypothesis. Advances in research on the pathological mechanisms of AD and advances in early diagnostic techniques may shift the time window for drug intervention and offer a potential pathway for developing effective drugs to delay the onset and progression of AD in the future.

Is targeting angiotensin-converting enzyme 2 (ACE2) a prophylactic strategy against COVID-19?

Prophylaxis against COVID-19 is greatly needed for vulnerable populations who have a higher risk of developing severe disease. Vaccines and neutralizing antibodies against SARS-CoV-2 are currently the main approaches to preventing the virus infection. However, the constant mutation of SARS-CoV-2 poses a huge challenge to the effectiveness of these prophylactic strategies. A recent study suggested that downregulation of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2 entry into human cells, can decrease susceptibility to viral infection in vitro, in vivo, and in human lungs and livers perfused ex situ. These findings indicate the potential to use agents to reduce ACE2 expression to prevent COVID-19, but the efficacy and safety should be verified in clinical trials. Considering ACE2 performs physiological functions, risks due to its downregulation and benefits from prophylaxis against SARS-CoV-2 infection should be carefully weighed. In the future, updating vaccines against variants of SARS-CoV-2 might still be an important strategy for prophylaxis against COVID-19. Soluble recombinant human ACE2 that acts as a decoy receptor might be an option to overcome the mutation of SARS-CoV-2.

Valemetostat: First approval as a dual inhibitor of EZH1/2 to treat adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell lymphoma with a poor prognosis. Accumulating trimethylation of histone H3 lysine 27 (H3K27me3) caused by upregulated function of either enhancer of zeste homologue 2 (EZH2) or its homolog EZH1 plays an essential role in the maintenance of transcriptional repression in ATL. Selective inhibition of EZH2 may complementarily induce EZH1 activation, so dual targeting EZH1/2 is a rational strategy in developing potent antitumor agents. Valemetostat is the first dual EZH1/2 inhibitor approved for treatment of aggressive ATL in Japan in September 2022. Several other dual EZH1/2 inhibitors such as HH2853, HM97594, and HM97662 have also demonstrated potential in treating malignant tumors. Dual targeting EZH1/2 may have promising antitumor action in hematological malignancies and solid tumors.