Forget transgenics for a moment. Large collections of inbred and outbred mice could be an untapped treasure trove for Alzheimer’s researchers.
At CTAD, investigational Phase 1 drugs include a repackaged and a new anti-amyloid, a tau vaccine, and a repurposed cancer drug.
At CTAD, a handful of candidate therapies were reported to have flamed out in Phase 2. They were unable to show efficacy. A new antipsychotic is entering the ring.
Several therapeutic approaches in Phase 3 reported updates at the CTAD conference earlier this month in Barcelona. Read about levetiracetam, deep brain stimulation, and scyllo-inositol.
The CTAD conference featured discussion among many scientists of how to measure a drug’s effect in pre-dementia patients who are so mildly impaired that established tools have trouble picking up improvement. Better cognitive tools are needed.
Both antibodies might be working, experts say, but the latest data released at the CTAD conference remain tantalizingly unclear. Trialists urgently need progression predictors and better outcome measures.
In a process known as repeat-associated non-ATG translation, neurons and glia make alanine, serine, cysteine, and leucine chains from the huntingtin gene.
Researchers report that an asparagine endopeptidase snips APP and promotes amyloid formation. They tout the protease as a therapeutic target.
Without the E3 ubiquitin ligase Idol, microglia readily gobble up ApoE and Aβ in a mouse model of Alzheimer’s disease.
Paralyzed mice recovered grip strength and balance when researchers turned off TDP-43.
Meet RBM45. This RNA-binding protein and relatively new player in the ALS field associates with stress-induced structures in the cytoplasm and nucleus.
A philanthropic organization has donated $177 million to train thought leaders from developing nations in dementia care and prevention.
Mice have fewer chromosomes than people, but their DNA is equally subject to natural variation. As reported at this year’s Society for Neuroscience annual meeting, researchers are beginning to capitalize on that diversity. They are using panels of inbred but genetically diverse mice to map variants that influence a variety of biological processes, including aging and memory. They have reported one find thus far, a gene for a heterochromatin-binding protein with links to autophagy. The hope is that the panels will help uncover genes that modify Alzheimer’s pathogenesis.
Have you ever been jolted wide awake by—biostatistics? That’s what happened one morning at CTAD. Suzanne Hendrix delivered a triple espresso in the form of a keynote calling on trialists to build cognitive composites to measure drug effects in early Alzheimer’s. In language that made statistics accessible beyond the geekdom of biostatisticians, Hendrix explained how power and regulatory factors prevent Phase 2 trials from showing whether a drug works. The status quo overprotects the null hypothesis that the drug is not working, she said. To boot, outcome measures are burdened by noisy items that do not reflect progression. The CDR-sb is meaningful but insufficiently granular to be a trials outcome. Hendrix’s solution: build lean composites with items that, in math lingo, add up to a “summed vector” that basically is the trajectory of worsening disease. Join Hendrix as she brings her argument alive on Thursday, December 17, at noon EST.
At the 8th Clinical Trials on Alzheimer’s conference held November 5-7 in Barcelona, 900 attendees traded results on trials from the closely watched Aβ antibodies aducanumab and gantenerumab to a long list of lesser-known therapeutic candidates. The most pressing issue discussed at this meeting was how to design trials to be able to see a drug effect in early AD, while the tools are still evolving. The field has learned much about the importance of rigorous dose-finding, exposure, and target engagement, but new frontiers have cropped up. How best to identify the right patient population, knowing how fast a given early-stage person is likely to progress, and measuring subtle improvement in barely impaired people have become the challenges of the day. To meet them, tools development is actively ongoing even as a larger clinical trials infrastructure is forming across both sides of the Atlantic.
The polyglutamine-containing proteins in Huntington’s and other triplet repeat disorders have a starring role in disease—but it turns out they may be part of an ensemble cast. Researchers discovered that neurons and glia sidestepped normal start codons to translate CAG trinucleotide repeats in all reading frames, churning out polyalanine, polyserine, polyleucine, and polycysteine. In some parts of the HD brain, these novel polypeptides even took center stage, overshadowing mutant huntingtin.
The E3 ubiquitin ligase Idol could be a new therapeutic target for Alzheimer’s disease, according to new research. Idol normally flags for destruction the low-density lipoprotein receptor, which removes ApoE from the brain. Animals lacking Idol retained more of the receptor, and cleared both ApoE and Aβ more efficiently. Researchers propose that targeting Idol could be a strategy for removing amyloid in people.
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