With the approval of Aduhelm (aducanumab, Eli Lilly & Co.) and Leqembi (lecanemab, Eisai Co. Ltd.), there are finally amyloid-targeting drugs available for Alzheimer’s disease (AD). What’s not available, though, are rose-colored glasses of the prescription strength that would make these approvals look like AD’s happy ending. The biopharma industry is already well aware of the need for broader horizons. Roughly three-quarters of drugs now in clinical development for AD target neither amyloid-β (Aβ) nor tau. Still, the genetic evidence from familial AD strongly implicates Aβ processing in AD’s origins. In his opening plenary talk at the European Academy of Neurology 2023 annual conference, Thomas Südhof suggested new ways to look at the clinical data.

At the 2023 Annual Congress of the European Academy of Neurology, Mary Reilly described the relationship between bench and bedside as “a continuous circle of translation,” with each cycle beginning with patients and their needs.

Researchers from Gat Therapeutics SL reported preclinical data for GTX-011, a first-in-class anti-inflammatory and antifibrotic drug candidate with properties mediated by the inhibition of the TGF-β pathway.

Monoacylglycerol lipase (MAGL) is a key regulator of the endocannabinoid system (ECS), which has a critical neuromodulatory involvement in numerous functional mechanisms in the CNS. Based on this, MAGL is considered a promising therapeutic target in neuroinflammation and neurodegeneration. Researchers from ETH Zürich and affiliated organizations have recently presented their work on (R)-[18F]YH-134, a novel reversible radiotracer for imaging MAGL in the brain.

Dopamine D3 receptors play a relevant role in the CNS modulating neurological activity, and its dysfunction is linked to disorders such as schizophrenia, drug abuse or Parkinson’s disease. There is a need for blood-brain barrier (BBB)-penetrant D3 receptor radiotracers with high brain uptake to be used for neurological and neuropsychiatric disease diagnosis.

Despite the success of CAR T-cell therapies for cancer immunotherapy, only a small percent of patients have a significant clinical response, and it is difficult to distinguish responders from nonresponders at an early stage with current imaging techniques.

Given the high prevalence of chronic kidney disease and the impact of renal fibrosis on the prognosis of these patients, there is a need for novel diagnostic tools to be able to detect pathological changes earlier and thus avoid progression to later stages of the disease.

Researchers from University North Carolina, Chapel Hill have discovered prostate-specific member antigen (PSMA)-targeted agents with reduced salivary gland uptake while maintaining high tumor uptake. Synthesis and subsequent screening of PSMA agents bearing different chelators and targeting ligands led to the identification of two lead agents, NOTA-UNC-PSMA-2 and DOTA-UNC-PSMA-2.

It seems unlikely that American poet and civil rights activist Maya Angelou spent much time thinking about translational research. But two quotes of hers capture the essence of the interplay between bench and bedside: “I did then what I knew how to do. Now that I know better, I do better” and “I’ve learned that I still have a lot to learn.” At the 2023 Annual Congress of the European Academy of Neurology, Mary Reilly described the relationship between bench and bedside as “a continuous circle of translation,” with each cycle beginning with patients and their needs.

National Taiwan University researchers reported the identification of a novel sorafenib derivative, SCB-24, which has the potential to be a new antimicrobial therapeutic.