MOFF | Cure ALS – Martha Olson Fernandez Foundation

OUR MISSION

The Martha Olson-Fernandez Foundation is committed to funding innovative research that aims to develop effectual treatments and ultimately find a cure for amyotrophic lateral sclerosis. The foundation is dedicated to raising awareness of ALS and providing financial assistance to underserved patients on the Central Coast of California.

WHY THE CENTRAL COAST?

While MOFF provides ALS research grant funding on a national level, MOFF patient care services are focused on the Central Coast of California. According the ALS Network, over 90 people are living with ALS on the Central Coast in any given period of time (2023). This is a large number when compared to the national prevalence rates: 9.1 per 100,000 individuals (CDC).

Additionally, interdisciplinary clinics are traditionally located in major cities such as Los Angeles and San Fransisco which makes access to high quality care difficult and require travel if you are located in between.

The overall financial burden of the disease can cost ALS families over $200,000 in out of pocket expenses per year (AJMC). MOFF efforts strive to offset these disease related costs.

Martha, loving wife, mother, daughter, sister, and friend to all, battled ALS for two years before it took her life. She vowed to never give up and her family promised to fight for her, and all other victims of this relentless disease, until a cure is found.

WHAT WOULD YOU LIKE TO LEARN MORE ABOUT?

ABOUT THE MOFF FOUNDATION

The Martha Olson-Fernandez Foundation (MOFF) is a 501(c)(3) nonprofit foundation that serves…

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WHAT IS ALS AND THE RESEARCH INVOLVED?

MOFF is energized by the novel and collaborative research that is ongoing…

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RESOURCES FOR PALS & THEIR FAMILIES

MOFF provide resources for people living with ALS so that their journey is a little easier than the journey…

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HOW TO GET INVOLVED

Would you like to learn more about how you can get involved in our fight against ALS?

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UPCOMING NEWS, EVENTS & RESEARCH

Learn about upcoming community events and new research in the fight against ALS…

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COMMUNITY EVENTS & RESEARCH UPDATES

ALS RESEARCH UPDATES, ALS NEWS & OTHER ALS EVENTS

ALS Inspire Series: Episode 1: Lauren Clausman

Lauren Clausman is running the TCS NYC Marathon this year for MOFF and Team ALS on November 3, 2024! We are very excited for her to undertake this 26.2 mile challenge and will be supporting her along the way! This will be the second year that MOFF is represented in the NYC marathon, in 2022 Samantha Fernandez completed this feat in 4:33:35. These women are our role models! Watch the video below to learn what inspired Lauren to run the 2024 TCS NYC Marathon. You never know, maybe she will inspire YOU to throw on some running shoes 🙂 Get to know Lauren better via the Q&A with her below: Q&A Where are you from and what is your spirit animal? I was born and raised in South Florida and currently live in Boca Raton. My spirit animal is definitely a dog!!! I love them all so much. If I had to narrow it down I would most likely say a golden retriever. Have you run a marathon before? Do you have a certain pace or completion time you are aiming for? This will be my 1st Marathon! I’ve completed a few half marathons in the last 5 years so I am hoping my body is ready. I would like to complete the NYC Marathon in a little under 4 and a half hours. You are running with Team Challenge ALS, what motivated you to support the ALS cause? How did you get connected with the Team? I am running in honor of Martha Fernandez and family is why I chose to do this. I don’t think ALS gets enough research and awareness and I am hoping to make a difference in that even if it is small. My cousin Natalie Fernandez was able to connect me with the ALS NYC Chapter and I was welcomed onto their team with open arms!!! The experience has been amazing thus far and I am looking forward to meeting my running team. Do you have any running idols or key people who support you that you would like to recognize? I can track my love for running all the way back to my pre-middle school days and seeing my mom run every single day. I quickly found my love for it and we were able to run together every day after school. It always reminds me of her and I think that’s why I still love it so much!! I can’t wait for her to see me cross the finish line just like my track and field days. Do you have any favorite running song recommendations for the MOFF community? ANYTHING disco or EDM is my go-to. Right now, Boom by Tiesto is how I start and finish every run. Learn about key information about the NYC marathon by visiting this website.
Centaur Trial (AMX0035): Longterm Survival Data

MOFF attended the NEALS webinar hosted by Dr. Sabrina Paganoni and Dr. Merit Cudkowicz on Wednesday, Oct 21, 2020. Click here to gain full access to the webinar once it becomes available. Background Information AMX0035 is a combination of two small molecule drugs: Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA). The Centaur Trial (NCT03127514) looked at the functional impact of AMX0035 on the ALSFRS-R score of people living with ALS vs. a placebo. The total trial enrollment was 137. The statistically significant Centaur Trial results are documented here. In short, the drug causes significant slowing of ALSFRS-R decline. The open label extension of the Centaur Trial was utilized to observe the impact of AMX0035 on the long-term survival of people living with ALS. The readout contained 35 months of data (beginning from initial trial enrollment period in 2017/2018). The readout came from a comparison of trial participants who took AMX0035 vs. those who were administered a placebo. Key Findings The following results were disclosed by the principal investigator of the Centaur Trial, Dr. Sabrina Paganoni, during the webinar: There was a 6.5 month longer median survival in the group originally randomized to AMX0035 than the placebo group. The median survival durations were 25 months and 18.5 months respectively. Please read the Oct 16th Amylyx Pharmaceuticals press release of their long-term survival data findings here. Both the placebo and non placebo groups had the option to take riluzole and/or endaravone. That being said, there was a sensitivity analysis done in both the function and survival studies. The sensitivity analysis concluded that AMX0035 had affects on top of the standards of care aka riluzole or endaravone. Q & A Q: Could this work for variants of ALS, such as primary lateral sclerosis (PLS)? A: Given the MOA of AMX0035, it is reasonable to think that it may be effective. However, no PLS patients were enrolled in the Centaur Trial. Q: What is the route of administration? A: The formulation used in the Centaur Trial was a powder form of both drugs that you mix with water. Q: Will it be affordable? A: Not determined at this time. Q: Will AMX0035 be available through Expanded Access? A: Not determined at this time. Q: Were there notable side effects? A: Mild nausea and diarrhea was common and expected in first 3 weeks of the trial.
Prop 14 (CA)

What’s all the buzz about Proposition 14? Why is the scientific community encouraging everyone to vote “Yes” ? Prop 14 plans to use debt to fund biomedical research: $5.5 billion in state general obligation bonds to be exact. The basic math is this: $5.5B granted today will accumulate $2.3B in interest. This interest will be payed back over 30 years in annual installments of $260 million by “Primarily General Fund tax revenue” aka, your taxes. How is the $5.5B being distributed? The grants will be distributed by the California Institute of Regenerative Medicine (CIRM) to “educational, nonprofit, and private entities for: stem cell and other medical research, including training; stem cell therapy development and delivery; research facility construction and associated administrative expenses”(Official Voter Information Guide). This debt funding concept is not new. Prop 14 is preceded by Prop 71 which awarded $2.7B in stem cell grants since 2004. That money was utilized for important cancer research projects at a time when the federal government refused to fund stem cell research. The catch? The research was supposed to pay for itself with projected revenues from successful therapies. That has not yet happened. Revenue projections aside, stem cell research is incredibly important to the ALS community. Please watch this webinar to hear experts discuss stem cell projects involving basic research and potential therapies for ALS that depend on Prop 14.
Novus Acquisition of Anelixis

The Martha Olson-Fernandez Foundation (MOFF) was very excited to hear that Novus Therapeutics had finalized its acquisition of of Anelixis Therapeutics this past September. Anelixis Therapeutics was the for-profit drug development arm of ALS Therapy Development Institute (ALSTDI) that was created specifically to develop their anti-CD40L antibody therapy for ALS known as AT-1501. An article published in BioSpace earlier this fall announced that Novus plans to “finance the advancement of Phase II clinical trials for AT-1501.” This is great news! Since 2016, MOFF has granted $105,000.00 to ALSTDI. In 2017, MOFF funding was earmarked to finance preclinical studies for AT-1501. The project was selected by MOFF due to the selective and specific nature of the AT-1501 antibody. These characteristics were a result of the years of development the potential therapy had undergone at the Biogen and later the ALSTDI labs. The MOFF board found the novel method of targeting the co-stimulatory pathway as an attractive investment. AT-1501 not only holds promise in ALS, but also for Type I Diabetes, and other neurodegenerative and autoimmune diseases. The MOFF board is looking forward to following the development of this therapeutic option. Learn more about AT-1501 in an ALSTDI Enpoints podcast episode here.
CRISPR and ALS

Brief Overview CRISPR is a highly specific and efficient genome editing technology. CRISPR facilitates the addition, deletion, or alteration of an organism’s DNA (NIH). If you would like a more specific explanation of CRISPR, feel free to watch the 1:39 video from the Mayo Clinic below. As one can imagine, this is exciting and simultaneously, terrifying technology. It holds incredible potential for countless rare, genetic diseases. The concept of curing a disease by removing a faulty gene, is not new, but CRISPR is definitely one of the more cost-effective and reliable ways to do so. Thus far, CRISPR technology has been tested on many rare disease areas, including cancers, sickle cell anemia, Huntington’s Disease, Alzheimer’s Disease, and ALS. In 2018, Target ALS provided CRISPR Therapeutics with a 2-year grant to study ALS and Frontotemporal Dementia (FTD). We are excitedly awaiting those results. Current CRISPR Challenges The success of CRISPR technology depends on the structural validity of in vivo disease models, meaning how well the animal model of the disease actually portrays the disease in humans. The ALS field has historically struggled with this issue. CRISPR success also depends on the capabilities of high throughput genome mapping technology, meaning, how much knowledge we have about the genome we will be editing. As we observe these two key elements (animal model validity and genome mapping technology) becoming more efficient and reliable, we will begin to see very obvious therapeutic results from CRISPR. Another roadblock to CRISPR’s usage in ALS is the fact that sporadic ALS is a messy disease. Messy meaning there are often a number of genes that contribute to the disease manifestation. Not only that, but these genes are not all ‘bad’ genes, but they are mutated in some way. For example, the protein C9orF72 is indicated in both familial and sporadic ALS. The normal function of this gene is to “influence the production of RNA from genes, the production of proteins from RNA, and the transport of RNA within the cell” (NIH). In ALS, C9orF72 is expressed as a hexanucleotide repeat expansion. If you program CRISPR technology to eliminate C9orF72, you may eliminate ALS, but you will also eliminate all the normal function of the protein, which could be deadly. CRISPR Breakthroughs Treatment of a Mouse Model of ALS by In Vivo Base Editing In this study done at the University of Illinois, ALS disease progression was slowed in mice when CRISPR was applied. Researchers utilized cytidine base editors (CBEs) to remove SOD1 gene expression. “CBEs are a type of CRISPR single-base editors that change specific nucleotide bases in a DNA sequence” (ALSNewsToday). The result of using this type of CRISPR technology is that it does not delete the SOD1 gene, but rather it induces a ‘stop’ signal early in the gene expression so that it cannot progress to be a mutant SOD1 gene. Very cool. The most common CRISPR headline you will see in relation to ALS is this one: CRISPR reveals possible ALS drug target In this particular study, a research team at Stanford used CRISPR to effectively ‘knockout’ or cut random genes out of the genome so that they observe “genes that protect neurons against the toxic effects of protein aggregates by being inactivated” (FierceBiotech). Their study revealed that “knocking out a gene called TMX2 prevented cell health in mouse neurons.” In the ALS world right now, finding possible therapeutic targets is a huge deal and most researchers are hard at work knocking out genes to do so. The final, and arguably the most exciting, CRISPR breakthrough is highlighted in these two articles: CRISPR-based method allows for reversible RNA editing RNA-targeting CRISPR could yield treatment for Huntington’s and ALS. The methodology behind this concept is mind-blowing. This article is from 2017, but they are still fine-tuning the science today. Researchers at the Broad Institute have dubbed the technology: REPAIR (RNA Editing for Programmable A to I Replacement). How does it work? To start, one has to understand the basics of transcription and translation. Here is a crude summary: DNA is transcribed to RNA which is then translated into proteins. This technology does not cut DNA, but instead, it binds to RNA and effectively changes one nucleoside in the RNA helix. Therefore, when RNA goes to translate into a protein, it will encode for a properly functioning protein instead of a mutant protein involved in disease progression. Amazing. Woof, that was a lot of science. Thank you reading if you made it to the end. To conclude: CRISPR Technology holds incredible potential for ALS and other rare diseases. Researchers just need to perfect it in a lab so that when it is applied to humans, no one comes out missing a limb :).

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