“Hot and cold tumors may need different types of immunotherapy,” Jay Berzofsky told the audience as the American Association for Cancer Research’s (AACR) 2024 annual meeting kicked off this weekend.  In an educational session on cancer vaccines, Berzofsky, who is head of the National Cancer Institute’s Molecular Immunogenetics and Vaccine Research section, explained that when immunotherapy fails in hot tumors, it fails despite the existence of an immune response, due to an immunosuppressive microenvironment.

As with most common diseases of the developed world, aging is the major risk factor for developing cancer. Most of the half-dozen hallmarks of precancer that were published last week by investigators from Vanderbilt University and the Fred Hutchinson Cancer Research Center are also hallmarks of aging. Unfortunately, scientists reported at the American Association for Cancer Research’s (AACR) 2024 annual meeting this week that accelerated aging is increasing, and may be driving an increase in early-onset cancers.

After decades of trying and dozens of failed trials, amyloid targeting has paid off with the first disease-modifying agents reaching the market. But success does not mean slam dunk. Aduhelm (aducanumab, Biogen Inc.) was dogged by controversy throughout its brief tenure, and Biogen pulled the plug on it in early 2024. Leqembi (lecanemab, Biogen Inc.) has received full approval. In this second installment of a three-part series on Alzheimer’s, BioWorld looks at the nuanced view of amyloid’s role in the disease.

At a recent meeting on “Research priorities for preventing and treating Alzheimer’s disease and related dementias” (ADRD), convened by the National Academies, one consensus priority on ADRD research was that there needs to be more of it at every stage. Several speakers presented stark numbers on the relative volume of research in cancer and neurodegeneration. Research output, measured in peer-reviewed papers, for dementia is estimated to be around 10,000 papers annually, compared to 150,000 for cancer, while AD clinical trials are also few and far between compared to cancer trials. This final installment of BioWorld’s series on Alzheimer’s explores some of the reasons for this discrepancy along with the latest advances and ongoing efforts to accelerate research and drug development in the field.

Ironically, the first person to be diagnosed with what is now Alzheimer’s disease was missing its major risk factor. When she first began showing symptoms of dementia in 1901, Auguste Deter was not particularly old. Despite Deter’s case, aging is the largest risk factor for developing Alzheimer’s, by a large margin. But “geroscience has not been translated into drugs for Alzheimer’s disease,” Howard Fillit, Alzheimer’s Drug Discovery Foundation co-founder and chief scientific officer, told BioWorld. “We’re just starting to see that cross-fertilization now.”

After decades of trying and dozens of failed trials, amyloid targeting has paid off with the first disease-modifying agents reaching the market. But success does not mean slam dunk. Aduhelm (aducanumab, Biogen Inc.) was dogged by controversy throughout its brief tenure, and Biogen pulled the plug on it in early 2024. Leqembi (lecanemab, Biogen Inc.) has received full approval. In this second installment of a three-part series on Alzheimer’s, BioWorld looks at the nuanced view of amyloid’s role in the disease.

Ironically, the first person to be diagnosed with what is now Alzheimer’s disease was missing its major risk factor. When she first began showing symptoms of dementia in 1901, Auguste Deter was not particularly old. Despite Deter’s case, aging is the largest risk factor for developing Alzheimer’s, by a large margin. But “geroscience has not been translated into drugs for Alzheimer’s disease,” Howard Fillit, Alzheimer’s Drug Discovery Foundation co-founder and chief scientific officer, told BioWorld. “We’re just starting to see that cross-fertilization now.” This first article of a three-part BioWorld series on Alzheimer’s disease looks at how a group of researchers, as well as some startups, are trying to approach Alzheimer’s via an aging lens.

Precision psychiatry got some love at two quite different meetings this week, the European Congress of Neuropsychopharmacology’s New Frontiers meeting and BioEurope Spring. The New Frontiers Meeting, an annual two-day meeting dedicated to cutting-edge issues in brain disease research, focused on big-picture and scientific – at times almost philosophical – questions of how to get to a classification scheme for brain disorders that aligns with the underlying biology.

To Steve Hyman, the manual that clinicians currently use to diagnose mental disorders is an active obstacle to getting a scientific understanding of those disorders. Hyman, who is director of the Stanley Center for Psychiatric Research at the Broad Institute, MIT and Harvard, and a former director of the National Institute of Mental Health (NIMH), listed multiple weaknesses of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM), whose diagnoses, he said, are “arbitrary, rigid, life-stage and context-insensitive,” as well as blind to the fact that mental disorders exist along a continuum.

In cell and animal models of amyotrophic lateral sclerosis (ALS), the expression of toxic dipeptides in neurons led to changes in the extracellular matrix (ECM) as a protective response. The authors wrote that their findings, which appeared in Nature Neuroscience on Feb. 29, 2024, could suggest new strategies for how to approach ALS.