Category Archives: ALS Research Events

2022 Hike x Brunch

The Martha Olson-Fernandez Foundation Annual Hike x Brunch

  Saturday, February 26, 2022 and Sunday, February 27, 2022

Thank you to all donors, MOFF hikers, random SLO hikers, silent auction donors and winners, and social media giveaway participants and winners!

Traditional Hike: Over 50 MOFF associated hikers completed either Felsman Loop or Bishops Peak in SLO and brought roses either to the peak or to Martha’s memorial bench. The MOFF team was present at the trailhead from 9:00 AM – 11:30 AM PT on Saturday and Sunday. Many people who were initially unfamiliar with MOFF also opted to take a rose with them on their hike to help us raise awareness of ALS. It was a beautiful weekend to do so!

Virtual Hike: Over 60 Instagram/Facebook users tagged @moff.cureals and hashtagged #cureals #nevergiveup in their hiking stories! It was a tough competition, but in the end, Nancy Walter and Courtney Crawford won the social media giveaway! Thank you to all of our virtual participants for raising awareness in your communities! MOFF supporters hiked in NY, CA, AZ, TX, HI, MX and the UK! Visit the MOFF instagram and view these stories in our highlights section.

Other Ways to Participate

Silent Auction: Congratulations to our Silent Auction winners! Participants were represented in 5 different states!

Donate: Together we raised over $15,000 to support MOFF’s ALS Patient Care and Research Programs! Way to go!

Why We Hike

This event honors the life of Martha Olson-Fernandez and every other individual who can no longer hike due to the effects of a neurodegenerative disease. Martha was a well-known SLO community member and an avid hiker when she was diagnosed with ALS in 2011. Her memory lives on through this MOFF community and her family and friends. It is through Hike x Brunch event that we are able to reflect on the lives of the incredible individuals the SLO community has lost to ALS and send strength to those who are living with the disease today.

Thank you to the SLO families that have participated in the MOFF Hike x Brunch since the 1st Annual in 2015 and to all of you who have joined us along the way!!

ThinkALS Tool

The ThinkALS tool was developed by the ALS Association to assist clinicians in the ALS differential diagnosis process. On average, ALS takes one year from time of onset to a definitive diagnosis. The obvious reason a rapid diagnosis is not possible is that a diagnostic biomarker for ALS does not yet exist. That is to say, you cannot run a lab test on a nasal swab and detect ALS, but rather every other condition must be ruled out first. Conditions commonly confused with ALS include spinal muscular atrophy, peripheral neuropathies, infections such as Lyme disease and hepatitis C that cause muscular weakness, Parkinson’s Disease, and behavioral variants of frontal temporal dementia. If you are interested in reading more about the ALS diagnostic delay and potential solutions, we encourage you to read the previous MOFF blogs listed at the bottom of this post.

MOFF will be distributing this ThinkALS tool to primary care practices in 2022 in an effort to identify people living with ALS earlier and refer them to an ALS specialist (neurologist) as soon as possible.

Call to Action: Print and share, or email this tool to your primary care physician’s office. Start a conversation about ALS with your health care provider. The more we talk about it, the more awareness we will raise, and the earlier ALS patients can get the medical team they need.

Click the image above to access the PDF version

For further information on the ThinkALS tool, visit this webpage.  

A Solution to the ALS Diagnostic Delay

1 in 300

The Don Woodward ALS Research Grant Sponsorship

Who is Don Woodward?

Don Woodward is a legendary member of the San Luis Obispo, CA community. He was an incredibly talented football player, golfer, and businessman. His name is well known in the California car industry where he started his business career at one of his grandfather’s dealerships, Lompoc Honda. Don’s name is one that brings a smile to everyone’s face that knew him and “f*#k ALS” energy to those who understand he was taken when he had much more life to live. Don’s wife at the time, Maggie Woodward, selflessly cared for Don throughout his ALS journey. She remains a pillar of strength and provided Larry Fernandez valuable guidance when Larry was going through his caretaking experience with Martha. The burden of ALS on families is palpable. The Woodward and the Fernandez families had everything you need to make the most out of the time you have left: love, humor, and Don and Martha.

Friends of Don golf in the Martha Olson-Fernandez Foundation (MOFF) Annual Golf Tournament and the “Woody” tournament at the San Luis Obispo Country Club each year. His memory truly is kept alive by his family, friends, and the golfing community. His friends, John Ronca and Scott Dierks, work closely with MOFF. John has served on the MOFF board for the past 2 years.

Why does the Don Woodward ALS Research Grant exist?

The grant exists to connect the golfers and sponsors that participate in the MOFF Annual Golf Tournament fundraiser directly to an ALS lab. When Martha outlined MOFF’s mission in 2012, she wrote on a piece of paper that “All funds go to research.” This grant is our way of making sure the MOFF community stays rooted in our mission and that our donors feel that connection to the research projects that are creating potential therapies for this brutal disease.

What labs have received this grant money ($10,000) in the past?

2019: USC Ichida Lab for ALS (Dr. Justin Ichida)

2020: Duke University ALS Lab (Dr. Richard Bedlack)

2021: The ALS Cure Project at Lawrence Livermore Labs (Mike Piscotty)

How do I apply to have my lab considered to be the recipient of the Don Woodward ALS Research Grant?

Email moffoundation@gmail.com and ask for our request for proposals (RFP) application. The deadline for proposal submissions is July 1st each year. Grants winners will be announced in September and grant funding will be distributed in February of the following year.

How do I become the Don Woodward ALS Research Grant Sponsor?

MOFF encourages any individual or company to become the Don Woodward ALS Research Grant Sponsor. Sponsors will have the opportunity to tour the ALS research lab that is selected and discuss the project with the researcher. Sign up to receive notifications from MOFF here. MOFF will announce the opening of registration for our annual golf tournament event in July. Once you receive notification of the golf tournament event, simply sign up via our event platform that will be listed in the email. Alternatively, email moffoundation@gmail.com and announce your intention to be the sponsor.

 

A HUGE special thanks goes out to Larry Fernandez who has been the Don Woodward ALS Research Grant Sponsor for the past 3 years. Thank you, Larry for your continued support!!

MGH Expanded Access Protocol (EAP) Program

The Martha Olson-Fernandez Foundation will donate $30,000 from their upcoming 9th Annual Golf Tournament (02-Oct) to the Expanded Access Protocol (EAP) Program at the Healey Center for ALS at Massachusetts General Hospital. Here’s why:

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease that affects roughly 9 out of a 100,000 people in the United States at any given time1. Put in more relatable terms, the average person has a 1 out of 300 chance to develop ALS in their lifetime 2.

There are currently only 3 FDA approved therapies indicated in the treatment of amyotrophic lateral sclerosis (ALS). These drugs, RADICAVA®, NEUDEXTA®, and Rilutek fall short of providing significant, disease modifying effects for those living with the disease. Those individuals that seek a more significant therapeutic benefit and a better chance at survival enroll in clinical trials. There are currently 86 global clinical trials that are currently recruiting patients3. The caveat is that nearly 60% of ALS patients fail to qualify for clinical trial enrollment due to the rigid inclusion/exclusion criteria written into each trial protocol.4  Expanded access, also called “compassionate use,” provides a pathway for patients to gain access to investigational drugs, biologics, and medical devices used to diagnose, monitor, or treat patients with serious diseases or conditions for which there are no comparable or satisfactory therapy options available outside of clinical trials.5

2020 statistics provided by the Golden West Chapter of the ALS Association revealed that there were just over 90 patients living with ALS on the Central Coast. These patients, right in our backyard, are dying. Their only chance is experimental therapies. The MGH Expanded Access Protocol (EAP) provides just that. Since the second quarter of 2018, The MGH EAP has supervised 133 ALS patients receiving access to therapies not yet approved by the FDA. These patients have seen therapeutic benefits and their stories of function recovery are inspiring.

Some of the drugs the EAP at MGH allows access to are currently being tested in the Healey Platform Trial: Verdiperstat, CNMAu8, and Pridopidine. All of these drugs are administered under the supervision of an interdisciplinary team of doctors and longitudinal data is collected for research purposes to assist with therapy validation and categorization.

This fundraising effort is a partnership between the Ken Brenner Family and the Martha Olson-Fernandez Foundation. To date, they have raised $6,900.00 and they need your help to reach their $30,000 goal. Since it costs $10,000 to provide 1 patient access to therapy for 1 year, this total will fund 3 patients.

NEVER GIVE UP

Donate to the MGH EAP Program today.

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567553/
  2. https://www.neurologylive.com/view/an-overview-of-causes-and-risk-factors-for-als
  3. https://clinicaltrials.gov/ct2/results?cond=ALS&Search=Apply&recrs=a&age_v=&gndr=&type=Intr&rslt=
  4. https://alsnewstoday.com/news-posts/2019/01/21/new-eligibility-criteria-needed-to-improve-als-trial-outcome/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443564/

9th Annual MOFF Golf Tournament: October 2, 2021

 
 

Thank yous, tournament prizes, and silent auction prizes will be sent to the event participants throughout October. 

Click here to view event results

COVID-19 Notice: We are excited to see everyone out on the course! In order to keep everyone safe, we are encouraging that all of our golfers, volunteers and visitors have negative Covid-19 tests. If you are experiencing any symptoms we respectfully request you refrain from attending.

The 9th Annual Martha Olson-Fernandez Foundation Golf Tournament has ended.

Special thanks to all the golfers, sponsors, and volunteers that made this event possible. 

Golfer and Volunteer FAQs

Q: Where is the tournament?

 A: Cypress Ridge Golf Course in Arroyo Grande, CA

Q: When is the tournament?

 A: Saturday, October 2, 2021

Q: When does check-in open?

A: 9:00 AM

FYI There will be a putting competition happening during check-in.

Q: When does the tournament start? 

          A: At 10:00 AM. Please arrive no later than 9:45 AM if possible!

          Q: Will breakfast and lunch be provided?

A: Yes! Coffee and breakfast burritos will be available at check-in and DePalo and Sons will be providing lunch. Please let us know if you would like a vegetarian option!

Q: What course games will be available? 

A: Closest to the Pin, Beat the Pro, Longest Drive, Hole-in-One, and more!

Q: How will the winners be determined? 

A: The top 2 scoring teams out of Net scoring category and top 2 teams out of the Gross scoring category will be selected at winners! There is also a hackers prize.

Q: Will there be an awards ceremony this year? 

A: No. Winners will be announced via email, on this webpage, the MOFF instagram account, and the MOFF FB account.

Q: Can I golf next to my friend’s foursome? 

A: Yes! Call or text Victoria at 805 458 9673

Click the registration form image below for more tournament details.

Click to navigate to the gt event page

2021 Fiesta Dinner

Welcome to the Martha Olson-Fernandez Foundation Fiesta Dinner

This event is held each year to honor the winner of the Fiesta Raffle at the Martha Olson-Fernandez Foundation (MOFF) Golf Tournament. The winner of this year’s dinner was: Sean St. Dennis! All raffle earnings were donated to the ALS Association Golden West Chapter and were earmarked for patients living on the Central Coast of California. This funding is incredibly important. ALS can cost a single family up to $200,000 of out of pocket expenditures a year.

We are honored to host Sean and Patty St. Dennis and their guests. We hope everyone has a wonderful evening!

2021 Virtual Hike x Brunch Event

Thank you to all the participants of the 2021 MOFF Hike x Brunch! This year, we had hikers tuning in on their Facebook and Instagram accounts from San Luis Obispo (SLO), Danville, Marin, San Francisco, the OC, Lafayette, Cayucos, Morgan Hill, Irvine Hills, Santa Monica, Atascadero, Washington, and New York City. The winners of the instagram giveaway were: Caroline Chalmers and Rachel Dettmer! They won MOFF swag and a gift bag from Bronze Sun Spa in SLO.

We are incredibly grateful to the silent auction item donors and silent auction participants. The virtual silent auction took place on the MOFF Hike x Brunch event site and was a great success!

It was wonderful to see all the hikers who stopped by our MOFF table at the Patricia Street entrance of Felsman Loop in SLO. We had roses in place for hikers to take up to Martha’s memorial bench on the loop.

The Splash Cafe brunch boxes were a hit! Thank you to all the hikers who preordered brunch boxes and picked them up after their hike. $4 from each brunch box purchase went to MOFF.

Thank you to Cafe Andreini for giving away free coffee to raise awareness of ALS in our Central Coast community!

This event happens annually to raise awareness of ALS in our community and to raise money to fund ALS patient care and research. Martha was an avid hiker- we encourage everyone to go on an adventure and hike for all those with ALS who cannot hike anymore.

Meet the MOFF Event Planning Intern: Victoria Humphrey

Victoria Humphrey will be joining the MOFF team this month! We are very excited to welcome her into our event planning efforts as we work to raise money to fund ALS research and patient care initiatives! Read a brief interview with Victoria below.

Q: Where are you attending college and what is your major?

A: I am a Cal Poly student majoring in Experience Industry Management with a  concentration in Event Planning

Q: Why does event planning at MOFF interest you?

A: While planning events is an intriguing job, being able to plan events for MOFF that  contribute to finding a cure for ALS is both intriguing and fulfilling work that I am excited to take on!

Q: What is your favorite fitness activity?

A: My favorite fitness activity is cheerleading as I was a collegiate cheerleader for the past four years

Q: What is your favorite slocal hangout?

A: My favorite place to hangout with friends and family is Avila Beach.

Q: Where you see yourself in 5 years?

A: In 5 years I see myself starting my own business, planning and executing events for causes I find passion for.

Q: What are you surprisingly good at?

A:  I am surprisingly good at calligraphy, I love using this skill to make home decor.

PSA: The final question to this interview may seem rather dark because it deals with death. That being said, the fatal nature of ALS brings death to the forefront and causes people living with ALS and their caregivers to grapple with the concept on a daily basis. MOFF has been operating as a grant making nonprofit within this space for 8 years now. We have seen too many incredible people have their lives cut short because of ALS. It is important to bring the urgency associated with living life in the face of death into our fundraising efforts. 

Q: What is your relationship with death?

A: Death used to be my greatest fear, but after experiencing more deaths within my life I have grown to appreciate it. Death is still something I fear, but I have accepted that without it life is not as extraordinary. 

What Happened in Guam? (Halloween Edition)

Classic Halloween stories have a spooky setting (like a haunted house or an abandoned log cabin), a deranged animal, and a full moon. While the story you are about to read doesn’t contain any of these elements, the reader may argue that it’s spookier, because it’s real.

Let us begin. The setting is in present day, Umatac, Guam. To most, Guam is a beautiful island in the South Pacific that is utilized by the U.S. military for its strategic positioning. If you talk to any scientist that studies neurodegenerative diseases, they would not site Guam’s natural beauty, but rather, they would allude to Guam’s dark medical history. One that has puzzled the scientific community for years. According to a 2017 article written in Penn Medicine Magazine, 1904 was the date the first official reports documented a peculiar disease that was plaguing the Umatac community. It is said that folklore reaching back two centuries documented cases of the same symptoms: “tremors, paralysis of the arms and legs, missed memories, and bouts of dementia” (Penn Medicine Mag 2017).

The Chamorro people are the locals of Guam. They called the disease lytico-boding, which alluded to the paralysis and listlessness that characterized the disease. The more formal scientific name is amyotrophic lateral sclerosis-parkinsonism-dementia or ALS/PDC. Lytico-boding was a very fast progressing disease that affected the islanders from age 15 to age 50. In 1954, it was the leading cause of death among the Chamorro people. A 1954 article in the Neurology Journal reported the incidence rate of lytico-boding to be “50-100 times that of the global average for ALS during this time.” That’s insane!

It is truly spooky. Luckily, the rate of disease has decreased significantly in the past decade, but that doesn’t erase what caused the disease in the first place.

Scientists have studied the disease for nearly a century and still have no definitely answers. That is certainly not due to a lack of hypotheses or funding. Parties involved in trying to solve the Chamorro people’s medical mystery have included the National Institute of Health (NIH), the Department of Defense (DOD), multiple academic institutions, and scientists from various disciplines. Notable researchers who have studied lytico-boding include:

John Q. Trojanowski, Dr. Gerard D. Schellenberg, Dr. Leonard T. Kurland, Majorie Whiting (anthropologist), Dr. Peter Spencer, Dr. Paul Cox, and Dr. Oliver Saacks.

Scientific hypotheses have all pointed to environmental factors such as the cycad seeds that the villagers consumed, military waste, poor eating habits, or interfamilial marriages. The Chamorro people have their own theories, such as the disease is the aftermath of a curse from an angry Catholic priest. A popular, more recent theory, developed by Dr. Paul Cox was featured in the February 2019 edition of Fortune Magazine. His research points to the high concentration of ß-N-methylamino-L-alanine (BMAA) that remained in the fat tissue of the bats that the Chamorro people ate as a delicacy. Dr. Cox affirms that a small molecule amino acid known as L-serine can combat the affects of BMAA. He is currently  involved with two Phase II trials of L-serine, one for ALS, and one for Alzheimer’s disease (AD). He believes L-serine will prevent neurofibulary tangle formation in AD and increase ALSFRS-R scores in ALS patients. The video below explains his research in Guam and in the U.S.A. further.

While lytico-boding has been useful for developing questions and theories of other neurodegenerative diseases, the mystery remains unsolved and downright SPOOKY. For more information on the medical mysteries of Guam, click here to read Steve Graff’s complete article.

HAPPY HALLOWEEN

If you are interested in more cases of neurodegenerative disease clusters. Check out the link below.

ALS Clusters in Japan 

Healey Platform Trial Monthly Updates

The clinical operations team involved with the Healey Platform Trial is truly going above and beyond the typical level of transparency. They have promised to host informal weekly Q&A sessions and will also hold monthly updates on the platform trial. If you would like to register for any of the weekly Q&A sessions or monthly updates please visit the Massachusetts General Hospital (MGH) websiteTheir website also contains basic information about the trial, details on the 5 therapies being tested, and a library of previously recorded webinars.

Thank you to the individuals from the ALS patient and scientific communities that are involved in elevating the bar for ALS clinical trials. Thank you specifically to MGH, NEALS, and Berry Consultants. This is truly exemplary.

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.

Raising Local ALS Awareness

The New Times SLO recently published an article on The Martha Olson-Fernandez Foundation. The reporter, Karen Garcia, does a good job of touching on the origins of MOFF, providing a glimpse into the annual events, and highlighting MOFF’s two critical programs: ALS patient care and research.

MOFF is constantly working to raise ALS awareness in the San Luis Obispo (SLO) community. If you live in the SLO community and are interested in this initiative, please reach out to us via our “Get Involved” page.

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 :).

COVID-19 Impact on ALS Clinical Research

depict COVID-19

COVID-19 Impact on ALS Clinical Research as of July 23, 2020


Of the 95 ALS clinical trials that are currently active in the United States, only 5 were suspended due to the COVID-19 pandemic. Also, many trials that were starting their enrollment back in March, have paused their enrollment processes for the time being. Overall, the ALS research community has been incredibly adaptable. Telehealth, laboratory shift work, and continued perseverance define today’s ALS research atmosphere. The staff at MGH working on the HEALEY Platform Trial has reassured everyone that they are hard at word on the behind the scenes protocol establishment and site readiness preparations.

We are all reminded that ALS does not stop during a pandemic. It is still 100% fatal. Every 90 minutes someone dies from ALS and every 90 minutes someone is diagnosed with ALS.

How I AM ALS is Influencing Clinical Trials Design

medical environment

I. What is wrong with the current ALS clinical trial landscape?

I am going to answer this question with a vignette: An individual with ALS decides to enroll in a clinical trial that they found on ClinicalTrials.gov. They check to see if they meet the trial requirements and are pleased to learn that the trial includes their type of ALS. Not only that, but the trial site is located close to their home and only requires one visit every two weeks.

This story is invented. It rarely happens that way.

Information about enrolling in ALS clinical trials is not readily available to recently diagnosed ALS patients. The trial information that is available, is not easily comprehensible for those not in the clinical research field. Even if a patient knew what a clinical trial was and started looking on clinicaltrials.gov, they would spend months sifting through phases, mechanisms of action, enrollment criteria and maybe, just maybe, they would find a trial that does not exclude them. How can you be excluded from a trial? Below is the exclusion criteria for a ALS dietary supplement trial that started in 2017:

  • Forced vital capacity <40% of predicted
  • Dependence on mechanical ventilation for more than 12 hours per day
  • Exposure to any experimental agent within 30 days of entry or at any time during the trial
  • Women who are breastfeeding, who are pregnant or are planning to become pregnant
  • Women of childbearing potential not practicing a medically accepted form of contraception
  • Enrollment in another research study within 30 days of or during this trial
  • Mini-Mental State Exam (MMSE) score <20
  • Patients with symptomatic cardiac disease or hypercholesterolemia
  • Patients with myocardial infarction within 6 months of this trial
  • Renal dysfunction defined as BUN and creatinine >2xULN
  • Known mitochondrial disease
  • BMI<18.5
  • Prior use of a 4:1 ketogenic diet or Atkins diet within 1 month of this trial
  • Impaired liver function, defined as AST or ALT of 3xULN
  • Patients who have a pacemaker or other internal electronic medical device
  • Known allergy or hypersensitivity to milk or soy products.

Yes, if you are allergic to soy you are disqualified from this trial…you get the point.

Exclusion criteria is only one of the many hoops ALS patients must jump through before they find the trial that is right for them. The length of ALS trials usually prevents the majority of patients from being able to complete them due to their rapid disease progression. Not only that, but what if you spent 6 months in a clinical trial in which you were a part of a placebo group? At that point, you spend 6 months not receiving an active drug, and you are probably disqualified from joining other trials. Okay, what if you are receiving the active drug? There probably weren’t any biomarkers that tracked your disease progression, so you would never know if your disease stopped progressing due to the drug or if you just had a slow progressing form of the disease. The list goes on…

II. What is I Am ALS?

I AM ALS is a patient-led ALS organization that was co-founded by Brian Wallach and his wife, Sandra Abrevaya, in 2019. Brian was diagnosed with ALS when he was 37 years old. He has an incredible story that has been told on several platforms. This video is a does a great job of visualizing it. I AM ALS empowers and enables people living with ALS. They are inserting the patient voice into politics and drug development and making sh*t happen. What exactly are they doing? I AM ALS has 3 key focuses: Advocacy, Patient Services (Navigation Program) and Research. This blog post focuses on their advocacy work.

III. What is I AM ALS doing to fix ALS clinical trials?

I AM ALS is visiting drug developing companies and introducing their Patient Centric Trial Design (PaCTD). What is PaCTD? It is a five star rating system that demands the following (this list is not exhaustive):

  • Scientific justification for all exclusion criteria
  • Minimization or elimination of placebo controls (e.g shared placebo group)
  • Use of biomarkers
  • Open label extension available for all trial participants
  • Use of novel methods for data capture
  • Unblinded Independent Intern Efficacy Review Board” (IRB) to review trial results while in progress to identify subsets of patients who are benefitting
  • Significant consideration for access to Compassionate Use (e.g Expanded Access)

The companies’ trial designs are rated according to how well they address the requirements in the PACTD. It is important to note that this rating scale does not in any way comment on the efficacy of the ALS trial. It is simply a way for people living with ALS to select the trial that most humanely considers their trial participants.

The PACTD requirements have the potential to impose serious financial strain on drug developing companies. They also have implications in the IND-enabling studies which happen well before Phase I clinical trials. That is why the I AM ALS constituents are meeting with drug developers early in their development process.

This is a time of true clinical trial innovation. I AM ALS is making drug development companies uncomfortable, but in the best way. In a way that demands critical thinking and promotes improvement. Patient centricity is not the end to profitability.