A new approach to treating amyotrophic lateral sclerosis and frontotemporal dementia (Sucrose octasulfate)

Medical Xpress / Academia Sinica / Science Advances ^ | March 18, 2024 | Yu-Jen Chang et al

[ConservativeMind]

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that commonly occur in middle-aged people. Both ALS and FTD arise from neuronal degeneration through mechanisms that remain unclear.

Dr. Yun-Ru (Ruby) Chen's team recently discovered a new pathological mechanism for neuronal degeneration using synthetic peptides. They also discovered that a disaccharide can increase neuronal survival and reduce degeneration. The result provides therapeutic strategies for future treatment.

ALS and FTD differ in clinical symptoms, but they share many pathological features and genetic variations. Clinical data shows that more than 90% of ALS and about 70% of FTD patients are sporadic cases, making it difficult to analyze. However, in cases found in the same family, the most common genetic mutation for both diseases originates from expansion of the GGGGCC (G4C2) sequence2 in the C9ORF72 gene.

The research team first used synthetic poly-GR/-PR peptides with different repeats. Experiments confirmed that repeats of poly-GR for more than 25–30 times reduced neuron survival and damaged cell and nuclear membranes. The study also found that the damage occurred through the interaction with nucleic acids, impairing important cellular functions such as DNA, RNA and protein synthesis.

The team further examined the structures of poly-GR and poly-PR using Small-Angle X-ray Scattering (SAXS).

Because mature neurons cannot proliferate, increasing cell viability is the goal of therapeutics for neurodegenerative diseases such as ALS and FTD. To identify possible therapeutics, the research team used a library of heparan sulfate molecules. From the screening, a sulfated disaccharide (sucrose octasulfate, SOS) showed the highest potency in reducing degradation of neurons from neuroblastoma and ALS iPSC-derived cells.

The team further found SOS can neutralize poly-GR/PR-induced neuronal degradation and demonstrated an improvement of motor behavior in Drosophila and mouse models. The result provides a possible future therapeutic strategy for ALS and FTD.

[ConservativeMind]

This is available today, on its own, but is used in impregnated wound dressings and in seemingly other limited ways.

[ConservativeMind]

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[Bob434]

that woudl be a huge breakthrough- I’ve known 4 people personally that have died from ALS- such a heartbreaking way to go- especially when they are younger, which the 4 i knew were- 40’s was the oldest-

as most know, Steve Hawking had it- it was incredible though how long he lived with it- but what a way to live- wasnt easy for sure-

[Ektelon]

I wish they were doing much more with ALS research.

My family has the familial ALS gene - and we’ve lost 17 (possibly more we don’t know about) family members from ALS.

Closest to me have been my grandfather and two of his brothers, as well as several aunts and uncles, and cousins of mine.

There could be others we don’t know about over the generations. My grandfather’s generation seems to be the first one to have it show up, but his great grandmother died in 1860 at age 30 of “paralysis”. I always wondered if it was ALS that nobody knew about then.

[coalminersson]

I keep seeing this demented guy on TV eating ice cream. That doesn’t seem to help.

https://www.alz.org/media/cacentral/dementia-care-45-the-power-of-ice-cream.pdf

[Bob434]

[[My family has the familial ALS gene - and we’ve lost 17 (possibly more we don’t know about) family members from ALS.]]

Wow- sorry to hear that- that’s rough-

[sneakers]

A coworker recently told me that he has ALS. He is already starting to have noticeable symptoms. I cried with him when he told me. He is in our maintenance dept and is going to hang on as long as he can. Our supervisors are working with him and helping him. A horrible disease. I hope they find a cure, or at least find a way to slow it down. He has a granddaughter who he loves so much and grieves at the thought of leaving her. He is only 54.

[ConservativeMind]

Here are a few studies of things that can help your friend, at least a bit:

https://medicalxpress.com/news/2023-06-omega-fatty-acids-linked-slower.html

https://medicalxpress.com/news/2022-12-probiotic-als.html

https://medicalxpress.com/news/2022-08-repurposed-drug-patients-motor-neuron.html

https://medicalxpress.com/news/2022-05-c9orf72-linked-dementia-mutant-mice-antibiotic.html

http://www.eurekalert.org/pub_releases/2010-12/uosf-bat122110.php

[sneakers]

Thank you! I’ll definitely pass those along!