Frank Shewmaker

Alector Announces Topline Results from Latozinemab Phase 3 Trial in Individuals with Frontotemporal Dementia Due to a GRN Mutation and Provides Business Update SOUTH SAN FRANCISCO, Calif., Oct. 21, 2025 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company focused on developing...

Disappointingly, the latozinemab trial for FTD-GRN failed to meet clinical endpoints (tinyurl.com/5f33sd88). However, the biomarker endpoint of elevated plasma PGRN was achieved. Perhaps PGRN localization to the lysosome, not extracellular fluids, is more critical for FTD-GRN (see PMID: 39565694).

Fantastic development from AC Immune: 2 promising small molecules for detecting TDP-43 pathology using PET imaging. There's currently no way to detect TDP-43 pathology in living patients with dementia or ALS. Could have a huge impact on future clinical trials.

pmc.ncbi.nlm.nih.gov/articles/PMC...

'I lost me': How frontotemporal dementia changed a mind and a marriage A Westlake Village man living with frontotemporal dementia has something few people with the condition do: the ability to describe his disease.

Excellent reporting from Corinne Purtill on frontotemporal dementia. "When someone is not who they were, think neurology before psychology” www.yahoo.com/news/article...

Gunman in Manhattan Shooting Claimed to Have CTE. How Do Doctors Search for It? (Gift Article) summary

Excellent reporting from NYT on the science of diagnosing CTE (and other tauopathies) in postmortem brain.
www.nytimes.com/interactive/... 🧪

A Breakthrough Beneath the Skin How a bold idea and smart federal investment created jobs, built a company, and is helping diagnose Americans in all 50 states.

Fantastic story about how NIH funding helped transform an unexpected hypothesis into a scientific breakthrough and a successful commercial biomarker assay for the diagnosis of Parkinson's disease and related disorders: www.ninds.nih.gov/about-ninds/75th-anniversary/cnd-life-sciences 🧪

Tofersen (Qalsody®) - Amyotrophic Lateral Sclerosis Amyotrophic lateral sclerosis (ALS) is a progressive and ultimately fatal neurodegenerative disorder that affects motor neurons responsible for initiating and controlling voluntary muscle movement and...

Over 3 decades of NIH-supported research enabled the FDA approval of Tofersen (Qalsody®), offering new hope for people with SOD1-related ALS. This breakthrough was made possible by unwavering, long-term societal commitment!
Timeline here: www.ninds.nih.gov/about-ninds/...

Progress with rapid & accessible biomarkers of neurodegeneration! Fujirebio received FDA clearance for a blood assay that predicts amyloid plaque pathology associated with Alzheimer's disease. The assay measures the plasma ratio of pTau217:β-Amyloid1-42.
www.fujirebio.com/en-us/news-e...
🧪

Fantastic series on the genetics of ALS from @thelancetneuro.bsky.social. Understanding these genetic subtypes will help therapeutic development for ALS and FTD.
tinyurl.com/544kx3fu

We are so excited for this year's AFTD Education conference! Come meet us in person, this Thursday and Friday. We have a table! See you all there ❤️

@theaftd.bsky.social

#curemaptftd #maptftd #ftd

Hi Monica, can I please be added? www.ninds.nih.gov/about-ninds/...

www.linkedin.com/in/frank-she...

We need biomarkers to detect TDP-43 loss-of-function in plasma! This will make earlier therapeutic interventions possible for many neurodegenerative diseases. Here's a funding opportunity from AMP ALS if you have a great idea:

fnih.org/wp-content/u...

A natural experiment on the effect of herpes zoster vaccination on dementia - Nature Using a natural experiment that avoids common bias concerns, this study finds that the live-attenuated shingles vaccine reduced the probability of a new dementia diagnosis within a follow-up period of...

www.nature.com/articles/s41...

Shingles Vaccine Can Decrease Risk of Dementia, Study Finds (Gift Article) A growing body of research suggests that preventing the viral infection can help stave off cognitive decline.

What's the easiest thing a 50+ yo could do to decrease their chances of getting dementia? getting the shingles vaccine! ~20% reduction over 7 years. Given the current lack of treatment/prevention options, this is a big reduction.

www.nytimes.com/2025/04/02/h...

Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures TDP-43 pathology characterizes neurodegenerative diseases. Scialò et al. use in vitro-generated and patient-derived TDP-43 aggregates as seeds to show that seed-induced TDP-43 cytoplasmic aggregation ...

Exciting back-to-back papers in @cp-neuron.bsky.social ! The combined work supports a prion-like mechanism for TDP-43 aggregation and cell-to-cell transfer. Once initiated, aggregated TDP-43 triggers LOF and GOF events.
www.cell.com/neuron/fullt...
www.cell.com/neuron/fullt...

A patient was diagnosed with corticobasal syndrome. BUT, neuropath exam showed frontotemporal atrophy with a-synuclein glial cytoplasmic inclusions and neuronal cytoplasmic inclusions. By cryoEM, the a-syn fibers look just like MSA fibers. Authors conclude "FTLD-synuclein" is a rare MSA subtype

An ‘Impossible’ Disease Outbreak in the Alps In one tiny town, more than a dozen people were diagnosed with the rare neurodegenerative disease ALS. Why?

The false morel mushroom is a suspect in this Swiss ALS cluster mystery.

www.theatlantic.com/health/archi...

Anti-amyloid drug shows signs of preventing Alzheimer’s dementia | WashU Medicine Clinical trial of people destined to develop early-onset Alzheimer’s disease shows eliminating amyloid from brain may prevent symptoms, supports need for confirmatory studies

Genetic carriers of a variant of early-onset Alzheimer's disease who were treated for 8 years (avg.) with an amyloid beta-directed antibody called gantenerumab had a 50% reduction in developing cognitive symptoms. 🧪

medicine.washu.edu/news/anti-am...

Study uses quanterix for NfL and GFAP

Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders - Molecular Neurodegeneration Background Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood gli...

NfL beats GFAP in a head-to-head FTD biomarker competition. Gendron et al. show plasma GFAP and NfL correlate with FTD disorder severity; however, NfL outperforms GFAP as a prognostic biomarker and potential susceptibility marker.

molecularneurodegeneration.biomedcentral.com/articles/10....

ALS molecular subtypes are a combination of cellular and pathological features learned by deep multiomics classifiers O’Neill et al. present a deep exploration of molecular subtypes in ALS postmortem tissues from the NYGC ALS Consortium. Matched bulk and single-cell profiles demonstrate that ALS subtypes are a combin...

Super happy to announce the latest work from my lab together with Hemali Phatnani @nygenome.org & NYGC ALS Consortium!

We've combined ALS patient profiling (100s!), ML classifiers and matched bulk/single-cell data to dive into ALS Molecular Subtypes

#NIHfundedResearch
www.cell.com/cell-reports...

Everything ALS is developing a study for monitoring and early detection of motor and speech changes. They're looking for participants who are gene carriers of ALS and are currently Asymptomatic.
www.everythingals.org/asymptomatic...

Congrats Martin!

Fantastic funding opportunity from AFTD to develop biomarkers for FTLD! $250,000 - $700,000 for 2 years! Better biomarkers will make diagnosis faster and help get patients into clinical trials.

www.theaftd.org/for-research...

FTD Biomarkers | AFTD See Active FTD Biomarkers Initiative Award Recipients

Fantastic funding opportunity from @theaftd.bsky.social to develop biomarkers for FTLD! $250,000 - $700,000 for 2 years! Better biomarkers will make diagnosis faster and help get patients into clinical trials. Please apply!

www.theaftd.org/for-research...

A reminder of the significance of multi-pathology in neurogenerative disorders. Imaging and fluid biomarkers are needed for clinical trial stratification.

Rare genetic disorder treated in womb for the first time Nature - The child, who is now almost three years old, shows no signs of the often fatal motor neuron disease.

A two-and-a-half-year-old girl shows no signs of a rare genetic disorder, after becoming the first person to be treated for the motor-neuron condition while in the womb.

https://go.nature.com/41rTube

Check out our new review of C9orf72 ALS in @thelancetneuro.bsky.social with Sarah Mizielinska, Rosa Rademakers and others! Was fun to co-write but tough to collate such incredible progress into a one article: authors.elsevier.com/c/1ke765FFzL...

Wow! Could be huge for biomarkers. AI tool uses six machine-learning models to analyze gene sequences encoding key regions in B-cell and T-cell receptors and pick out patterns associated with particular diseases.

A patient with a PSEN2 mutation should have had early dementia onset but didn't! Despite a high amyloid plaque burden there was limited tau pathology. Authors suggest tau pathology is the driver of dementia onset. Putative protective gene variants: FAM1515B, CEP290, GPCPD1, PRICKLE3, ANKRD36C.

Really appreciated Mike's expertise on NIH policies.