Erik Musiek on Donanemab Approval Likely to Pose New Quandaries for Clinicians

COMMENT I am pleased to hear the positive news on donanemab and agree that it is likely to be approved soon. Donanemab has some potential advantages over lecanemab, but also may have some weaknesses, so it will be nice for clinicians to have both as options. Cert

Erik Musiek on While a Fly Sleeps, Its Glia Burn Neuronal Lipids to Refresh the Brain

COMMENT This is an exciting finding. It builds on work from Hugo Bellen’s lab, which showed that astrocytes can take up lipid droplets from stressed/injured neurons as a neuroprotective mechanism. This new paper provides a novel connection to sleep deprivation, w

Erik Musiek on And Then There Were Three: Donanemab Phase 3 Trial Positive

COMMENT The top-line results from Lilly today are very exciting to me for several reasons. First, these data really strengthen the argument that plaque removal has a meaningful clinical effect in mildly symptomatic patients. With Phase 1b/2 trials for aducanumab,

Erik Musiek on Take a Deep Breath—It Just Might Lower Your Risk for Alzheimer’s

COMMENT I must commend these investigators for integrating plasma AD biomarkers into their study of a behavioral intervention. That they saw changes in these biomarkers with this relatively mild intervention is quite interesting and exciting. Interpreting those c

Erik Musiek on Dare We Say Consensus Achieved: Lecanemab Slows the Disease

COMMENT I’m cautiously optimistic about the lecanemab data. Because there is such mild decline in these patients over 18 months, it’s very difficult to see a positive signal, particularly when it takes several months to titrate the medication and remove the plaqu

Erik Musiek on Finally: Big Win on All Outcomes for Lecanemab in Phase 3 Topline Results

COMMENT These results are very exciting, though we all, of course, need to see the actual data before drawing any major conclusions. I think that the incomplete trials for aducanumab left the field at a tipping point: On one hand, the Phase 1b/2 trials for aducan

Erik Musiek on Drilling Down into the CMS Aduhelm Decision—A Primer

COMMENT I don’t think this coverage decision changes much. Practically, it’s a denial of coverage. I don’t know of any trials that would qualify for CMS support under these criteria that are not being run by Biogen (and thus already have free drug). Perhaps some

Erik Musiek on CMS Plans to Limit Aduhelm Coverage to Clinical Trials

COMMENT To me, the logic behind this proposed NCD is confusing. No one besides Biogen is likely to have the incentive or money to run another sufficiently large, randomized, placebo-controlled Phase 3 study of aducanumab. And Biogen is already doing this. Now, it

Erik Musiek on Deep Sleep Accelerates Synuclein Removal in Mice

COMMENT Morawska et al. have expanded upon previous studies showing that sleep enhancement/deprivation can influence Aβ and tau deposition to now show that the same holds true for α-synuclein. They have taken care to characterize the effects of sodium oxybate on

Erik Musiek on Could Restoring Deep Sleep by Jolting the Brain Ward Off Alzheimer’s?

COMMENT In this very interesting paper, Jagirdar et al. demonstrate both fragmented sleep and hyperactivity of the thalamic reticular nucleus in J20 APP transgenic mice. They use DREDDS to alter neuronal activity in this nucleus, thereby increasing slow-wave slee

Erik Musiek on Getting Too Little Sleep? You May Be Accumulating Amyloid.

COMMENT This nice study is consistent with several smaller previous studies linking self-reported sleep issues (in this case, short sleep duration) with brain amyloid level as assessed by amyloid PET. This study has a very large number of people with amyloid PET

Erik Musiek on How Will Aducanumab Approval Change Clinical Practice?

COMMENT Regardless of one’s opinion on the drug, the Aduhelm approval is likely to have a huge impact on research and clinical practice. Regarding clinical practice, I was very surprised by the broad indication from the FDA. It seems to fly in the face of all exi

Erik Musiek on Donanemab Confirms: Clearing Plaques Slows Decline—By a Bit

COMMENT The Phase 2 data on donanemab is encouraging and raises expectations for Phase 3 trials. The effect size on the primary endpoint (iADRS score) is considerable and very promising. However, secondary endpoints such as CDR-SB, ADAS-Cog13, and MMSE were less

Erik Musiek on Deep Sleep Makes Waves for CSF

COMMENT This is an exciting paper, which provides a possible mechanistic link between slow-wave neuronal activity during NREM sleep and pulsations in CSF flow. It offers a new insight into how sleep-related changes in neuronal activity potentially alter CSF dynam

Erik Musiek on Circadian Clocks Function in Concert with Heat Shock Organizing Protein to Modulate Mutant Huntingtin Aggregation and Toxicity.

COMMENT This is an interesting paper, and I think it is well-conducted and meaningful. An important takeaway is that circadian regulation of cellular function is complex, and the effects of clock disruption on measures of disease may be highly context-dependent.