Category Archives: MOFF Blog

2021 Virtual Hike x Brunch Event: February 27 & 28

It is that time of year! The MOFF Annual Hike x Brunch event is right around the corner. This year, the brunch portion of the event will be tailored to the comfort of your home and the hike component can take place at any hike destination near you. MOFF will be partnering with local breakfast establishments in San Luis Obispo county during the event weekend. Attendees will be able to preorder brunches options from Splash Cafe in SLO

When: February 27th & 28th

Where: Felsman’s Loop in SLO or at the hiking location of your choice

How to participate:

1. Preorder a Splash Brunch Box prior to the event here

2. Visit the Hike x Brunch event site here

3. Hike a mountain near you on Feb 27th or 28th

4. Take a picture at the top and tag @MOFF.CureALS on Instagram or Facebook and make sure to #alsawareness!

5. Pick up your preordered brunch at Splash Cafe

6. Have a wonderful weekend knowing that you hiked for the 90 people living with ALS on the Central Coast that can no longer hike anymore

Roses will be available at the base of Felsman Loop on Saturday and Sunday if you plan to hike to Martha’s Memorial Bench like we have done in previous years. The Fernandez Family will be hiking Felsman Loop on both days. We hope to see you there!

The virtual event site is live! We hope to see your photos and hear of your hiking journey soon.

Donations raised during the event will go towards ALS Research Project Grants and Grants for ALS Patient Care Programs on the Central Coast of CA.

Thank you for your support!

Donate

MOFF Response to Loss

The ALS community lost two incredible people this past Thanksgiving week. Leslie Sands (1951-2020) and Patrick Quinn (1983-2020). Our hearts go out to their families and friends. This is a difficult time for everyone during the economic and emotional hardship of COVID-19. Adding the painful loss of a loved one makes isolation that much more difficult. We will be sending prayers their way.

The statistics behind the fatality of ALS paint an image laden with loss:

Incidence:

Each year in the United States 5,000 people are diagnosed with ALS. This seems like a relatively small number until you start to look at the numbers in terms of the lifelong chances of an individual contracting the disease: 1 in 300.

Survival:

50% of those 5,000 individuals will live 3-5 years.

25% live 5 years or more and yet another 10% will live more than 10 years.

In the end, ALS is 100% fatal.

Thankfully, over the past 8 years, an increase in disease knowledge has led to slightly longer survival and higher quality of life. This is in part due to the now 4 FDA approved drugs for ALS: Riluzole, Radicava, Tiglutik, and Neudexta. These drugs are a step in the right direction, but they are not enough.

Emotional Rollercoaster: 

Every time we lose a member of this tight-knit community, everyone feels it. For people working to solve the ALS puzzle, it feels like the weight of a failure, the breathlessness of time running out, and the frustration of not being able to do enough to save that individual. Then, there is the subtle fear over how many people will die before a cure is found and the esoteric contemplation of why ALS exists and why it is so ruthless.

MOFF Response:

This roller coaster causes MOFF to operate like we are running out of time, because we are. We fund the most cutting edge research, and we grant money to patients to help improve their quality of life in whatever ways current care standards permit. We seek alliances within the ALS nonprofit community that allow us to connect ALS families to the services they need, and we work with ALS collaborations that aim to share ALS information and knowledge. When we lose a person living with ALS, we don’t stop, we keep going.

Clinical research is where we direct people living with ALS who are not satisfied with the current, minimally effective standards of care. Clinical research is what we emphasize will bring about the next effective treatment to ALS, because it will. There are currently 11 Phase 3 clinical trials that are recruiting in the U.S. We encourage all ALS patients that are interested in finding a cure, to participate in one of these trials. If you would like further information on navigating the clinical trial landscape or would like to speak with someone who has gone through the clinical trial experience, please email Natalie Fernandez at moffoundation@gmail.com

 

#GivingTuesday: December 1, 2020

#GivingTuesday is a nationally recognized day of philanthropic giving. According to the #GivingTuesday creators, it is a “global generosity movement.” Last year, the total amount that was donated to nonprofits in the U.S.A was $1,970,000,000.00! That is a pretty incredible number.

This year on #GivingTuesday, MOFF is emphasizing the urgency with which we need to invest in ALS research. Every 90 minutes someone dies of ALS. This has been happening since Lou Gehrig had the illness in 1939. Something needs to change, now. Every cent counts towards this fight.

Donate Today

In 2019, MOFF hosted a #GivingTuesday campaign that provided information on the below ALS FAQs.

Q: Does ALS have a genetic cause?

A: Yes. 10% of all ALS cases are caused by genetic mutations that are inherited from a family member. 90% of ALS cases are sporadic in origin which means the cause is unknown. That being said, there are some gene mutations that are implicated in sporadic cases, such as the C9orf72 gene. The plot thickens.

Q: How does “sporadic” ALS happen??

A: We wish we knew! There are many scientific theories surrounding sporadic ALS. Here are a few: Oxidative stress, mitochondrial dysfunction, glutamate toxicity and toxic exposure (occupational hazards, cyanobacteria etc.). Read more here.

Q: Has anyone survived ALS?

A: Yes! Dr. Richard Bedlack at Duke studies what he calls “ALS reversals.” There are 48 documented cases of ALS being reversed. MOFF has committed funding to Dr. Bedlack’s research on the microbiome of people who have “reversed” ALS for FY2021.

Q: Did the Ice Bucket Challenge help at all?

A: Yes. The ice bucket challenge raised $115M in the U.S. alone. Internationally it raised $220 M. $90 M of those funds have been distributed throughout the scientific community and have lead to identification of new pathological mechanisms and genetic causes of the disease. Here is a breakdown of the impact of those funds.

Q: What type of ALS did Martha have?

A: Martha had bulbar-onset ALS.

Q: Is ALS more common in men or women?

A: ALS is 20% more common in men than women. However, according to recent research, the incidence becomes more evenly distributed among gender with increasing age.

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 

ALS Research Paper Review (ALS RPR)

Natalie Fernandez is honored to be co-chair of the newly formed ALS Research Paper Review (ALS RPR) Platform. Her co-chairs are Phil Green and John Russo. Both John and Phil are incredible ALS Advocates and ALS Research Ambassadors. Collectively, Phil and John have been involved in pretty much every major ALS nonprofit org and ALS initiative that has brought about patient-driven change. That list includes I AM ALS, Team Gleason, EverythingALS, The ALS Association, and numerous patient and caregiver advisory committees. John Russo is the mayor/networker/diplomat of the ALS community per se and Phil should receive his honorary PhD in the mail any day now. His knowledge of ALS research and clinical trials is invaluable.

What is the ALS RPR? This initiative was suggested by a couple members of I AM ALS and NEALS and is intended to bridge the gap between scientific research papers and lay people working to understand the disease. The co-chairs plan to host an hour long session once a month in which we review a paper with the researchers that authored the study. Supplementary materials will be provided to assist with scientific and research concept understanding. Our goal is to provide a platform for an engaging conversation that pays respect to and fosters understanding of research within the ALS disease state.

Dr. Bedlack from the Duke ALS Clinic has graciously agreed to be our scientific advisor to help get the project off the ground. Thank you Dr. Bedlack 🙂

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.

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.

In the upcoming months, MOFF looks to do more to raise ALS awareness in San Luis Obispo (SLO). If you live in the SLO community and are interested in this initiative, please reach out to us via our “Get Involved” page.

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.

ALSA Patient and Caregiver Advisory Committee (PCAC) Involvement

Natalie Fernandez recently became a member of the Patient and Caregiver Advisory Committee (PCAC) at the National Chapter of ALS Association (ALSA). The PCAC is co-chaired by John Russo and Ken Menkhaus who are both incredibly knowledgable and influential ALS advocates. If you are interested in learning more about their perspective, Ken has a blog called, Ken’s Caucus. The PCAC currently has 20 members and each member serves two year terms. The purpose of the committee is to provide informed guidance to ALSA and the ALS Focus Steering Committee. Responsibilities of the committee members include: Generating survey topics, reviewing survey questions, and ensuring patient and caregiver authenticity.

Natalie is honored to be a part of the PCAC. ALSA staff works hard to provide care and support for ALS families. They are also the largest funder of ALS research projects in the world, which is pretty incredible considering they are a nonprofit. While Natalie is aware of the tension that exists between ALSA and more grassroots ALS movements, she is excited for this opportunity to focus and inform initiatives that directly affect families living with ALS. In the words of Sandy Morris, “We are all fighting for the same thing. When we find that we are fighting each other, we are on the wrong path.” It through collaboration and focus on our shared goal that we are going to find a cure for ALS.

1 in 300

1 in 300 is the lifetime risk of anyone developing ALS

This 1/300 statistic is important. Why? Well, there are many reasons why. This post addresses two of them.

    1. Public perception of ALS

The standard ALS prevalency statistic that people read is that every 5 people out of 100,000 people have ALS at any given time in the U.S. This is makes ALS seem underwhelmingly rare. This perception causes individuals displaying ALS symptoms, to rationalize their symptoms and delay doctor visits until their disease has taken a significant toll.

Have you every wondered why so many people have had family members or friends affected by ALS and you didn’t know about it until you had ALS hit close to home? Several factors affect this phenomenon, one being the short lifespan of an ALS patient (2-5 years on average).  Just because there are few people living with ALS in our community right now does not mean that people have not been affected by it. ALS is also a very private disease. It involves the lose of autonomy and the lost of every skill needed to interact with the general public. That paired with how fast the disease progresses is just enough to silence, confuse, suffer, and then disappear. The individual’s legacy will live on and the love for that person will persist, but the disease burden and the overwhelmingly rapid disease progression is enough to recede from the public view and then cease to exist. 

    2. Medical community awareness of ALS

ALS is notoriously missed in a primary care physician setting. Why is this? For starters, doctors are pattern recognizers. Depending on their practice, whether it is neurology, dermatology, or optometry, they are trained to look for patterns and ask questions or run tests to confirm or deny their suspicions. Unless you are an emergency room physician and trained to expect the worst, rare diseases are not the first diagnosis doctors jump to. A solution to this failure to recognize ALS early on is by increasing awareness of the prevalence of ALS. The medical community can do this by utilizing the 1 in 300 statistic. This would, in theory, increase a doctor’s index of suspicion towards the disease. Index of suspicion is defined as: “The level of suspicion that a disease or condition is the underlying diagnosis based on the available findings in a patient.” Just maybe, the 1 in 300 lifetime risk will allow a primary care physician to think that their patient’s hand weakness is not simply a weakness due to a localized sports injury, but maybe a more global issue with neurological underpinnings. 

Resources

ALISON GOWLAND1 , SARAH OPIE-MARTIN1 , KIRSTEN M. SCOTT2 , ASHLEY R. JONES1 , PUJA R. MEHTA1,3 , CHRISTINE J. BATTS4 ,CATHY M. ELLIS3 , P. NIGEL LEIGH5 , CHRISTOPHER E. SHAW6 , JEMEEN SREEDHARAN1 AND AMMAR AL-CHALABI1, (2019) Predicting the Future of ALS,

ALS/MND International Alliance Scientific Advisory Council Meeting

MOFF attended the ALS/MND International Alliance Scientific Advisory Council Meeting on June 17th (at 4 AM PST). It was worth it. The event was hosted by The ALS Association and featured neurologists from 10 different countries.

Who attended this International Advisory Council Meeting?

Dr. Jeanine Heckmann (South Africa)

Dr. David Taylor (Canada) – facilitator

Dr. Kuldip Dave (USA)

Dr. Nicolas Cole (UK)

Dr. Caroline Ingre (Sweden)

Dr. Gethin Thomas (Australia)

Dr. Piera Pasenelli (USA)

Absent: Dr. Qing Liu (China), Dr. Adriano Chio (Italy) and Dr. Luis Barbeito (Uruguay)

What did they discuss?

The main discussion topic was prompted by the facilitator, David Taylor. He began the meeting by encouraging participants to share what they are most excited about in the ALS/MND field. Responses varied, but there was a general consensus around 3 topics:

1. Platform trial design

The Tricals Platform Trial (UK) and the Healey Platform Trial (USA) design are both incredible tools to test new therapies for ALS. They are not only cost-effective, but time-efficient and patient-centric as well. The platform concept was originally implemented in oncology, and in 2019 was adapted to the ALS field. Historically, trials have required a 50/50 placebo control. In cancer and ALS, the fatality rate of these diseases make it almost unethical to put a patient in a placebo control group. The platform trial takes this into consideration; only 1/3 of patients will receive a placebo and for a shorter duration (6 months). The platform trial design allows for more therapy options to be tested at once: 5 for the Healey Trial and 2 for the Tricals Trial. The treatments being tested in the Tricals Trial are Lithium Carbonate and Triumeq. Read the MOFF article on the Healey Trial to learn what treatments are being used in the U.S. trial.

Dr. Pasenelli and Dr. Cole had a productive dialogue about comparing trial outcome measures. This discussion occurred after Dr. Cole claimed the Tricals Trial had more outcome measures than the Healey Trial. While this is likely because the FDA bases it’s outcome measures on the ALSFRS-R score and the EMA bases their outcome measure reporting on survival, a more thorough comparison is warranted.

2. Gene therapies

Gene therapies are the future! It is not an unrealistic claim to say that specific genetic forms of ALS will be curable within the next 2-5 years. Researchers are targeting ALS cases with the SOD1, FUS, and C9orF72 genetic mutations. Two examples of such therapies are Tofersen (Biogen) and AVSX-301 (Avexis/Novartis). Phase 3 trials of Tofersen are currently being conducted in the U.S. and multiple other countries including Japan, Canada, and Italy. The aims of these gene therapies are to replace genes, silence genes, or deliver proteins that boost motor neuron function. Currently, the two most promising ways to deliver these therapeutic benefits is via Adeno-associated viruses (AAVs) or Antisense Oligonucleotide (ASOs).

These gene therapies are the first to modify ALS disease progression. This is amazing given the fact the three current FDA approved medications for ALS simply claim to extend patients’ lives by 3 or 6 months. What is even more incredible about the development of gene therapies for ALS, specifically, Tofersen, is that Dr. Alan Smith wrote about this therapy in his book: Handbook of Amyotrophic Lateral Sclerosis. It was published in 1992. Patients are finally gaining access to treatments that have been conceptualized almost 30 years ago.

Keep in mind that these genetic therapies will only be effective for 10% of the ALS population. That being said, C9orf72 has implications in the sporadic form of ALS as well so whatever pathogenetic insights they extract from these ongoing clinical trials, will inform future studies done for sporadic ALS.

3. Biomarker usage

We can finally objectively measure if drugs are slowing ALS disease progression! “Biomarker” has been a buzz word in the ALS community for years. A biomarker, loosely defined, is a biological sample that can be used to screen, diagnose or monitor disease progression. The majority of  excitement during the meeting was centered on the use of pharmacodynamic biomarkers, in upcoming clinical trials. Below is an image of the many potential measurements of ALS disease progression that newer trials, specifically the Healey Platform Trial, will incorporate.

(Image adapted from a 2019 Mass General presentation on the Healey Platform Trial. The presentation was led by Dr. Sabrina Paganoni and Dr. Ben Saville)

For the sake of time and space, this post will not going into the details of each measurement. More information can be found in this Frontiers article. The second takeaway from council’s the biomarker discussion was one of hope. Dr. Pasenelli described an important perspective shift that has occurred in the ALS research community. To paraphrase, she recognized that 7-10 years ago, researchers joined the ALS therapeutic area for the general, rather unexciting discipline of researching. Now, each ALS research investigations could lead to a potential therapeutic target or a biomarker discovery. The hope of actually discovering something is alive and is encouraging more individuals to join the field. This was incredibly encouraging to hear.

Sidenote:

South Africa:  South Africa gets their own blurb because during the meeting it sounded like Dr. Jeannine Heckmann was on a literal ALS battlefront. She began the meeting by stating there are only 3 interdisciplinary clinics in South Africa and the some of the medical professionals attend the clinics once a month. Dr. Heckmann went on to share a very moving story about recent ALS diagnosis she had to give while the patient was already in need of a ventilator and there were limited ventilator resources. Their country has limited resources to Rilutek, which is 10-15 years behind USA standards. In conclusion, Dr. Heckmann is a saint and needs back up. Also, the South African ALS patient community needs support ASAP.

Thank you to all the ALS/MND Internationals Alliance Scientific Council Members! We greatly appreciate all of your contributions to the ALS field. 

 

 

A Solution to the ALS Diagnostic Delay

The amyotrophic lateral sclerosis (ALS) diagnostic journey is unique to each individual. It has puzzled neurologists, been mistaken for allergies or back issues by physicians, stressed out families, and most significantly, it has prevented patients from knowing what is affecting their body.

The median diagnostic delay for a person living with ALS is 12 months (Martharan, 2020). In other words, from the time of their first symptom onset, it takes roughly a year to positively diagnose someone with ALS. Not only that, but each person living with ALS sees an average of three different physicians before receiving their ALS diagnosis (Paganoni, 2014). In the world of rare diseases, this diagnostic delay is not uncommon, but on a patient level, this lag can be life threatening. Not only does the delay prevent patients from seeking the correct medical attention for their symptoms, but it also reduces the time frame a patient has to enroll in clinical trials.

So, if it really takes a year to get diagnosed with ALS, where does all the time go? According to peer reviewed literature, there are three key stages that have quantifiable lags (Paganoni, 2014).

    • Time from symptom onset to the first doctor visit: 4 months
    • Time from the first doctor visit to a suspected ALS diagnosis: 3 months
    • Time from suspected to confirmed ALS diagnosis: 1 month

Research studies have also been conducted to analyze what factors delay or accelerate an ALS diagnosis:

    • Patients age 60 and older: delayed ALS diagnosis
    • The presence of fasciculations, slurred speech, and lower extremity weakness when symptoms are first noted: accelerated ALS diagnosis
    • Sporadic ALS and limb onset: delayed ALS diagnosis

If we analyze the above diagnostic delay predictors in each individual ALS case, we can start to break down what really is at the root of a delayed diagnosis. Was it the patient’s stubbornness and refusal to go to the doctor? Was it a primary care physician failing to identify the patterns of a highly complex disease or not wanting to give a fatal diagnosis? More than likely, it was a culmination of multiple variables. The author of this blog has identified four key categories of dysfunction that influence the ALS diagnostic process: public knowledge, the medical system, the pharmaceutical industry, and ALS disease complexity. There are specific failures within each category. The charts below list these points of failure.

Compensating for each of these system failures will take, and is taking, years and millions of dollars. Is there a simpler solution? Or do we approach each of these system inefficiencies individually? Yes, there is a simpler solution. Machine learning is proving to be the solution. Mitsubishi Tanabe (MT) Pharma, the company known for developing the ALS therapy, endaravone, is hard at work. They have created a program that interfaces with billing codes within our medical systems. The software is trained to identify potential ALS patients before they receive their ALS diagnosis. How is this possible? MT Pharma acquired historical claims data on Truven from 14,000 ALS patients during the 5 years leading up to their ALS diagnosis. They looked for patterns in the billing codes and created an algorithm to detect similar patterns. This early detection software was in the beta testing stages in December 2019 and will hopefully be utilized in the near future. The early stage testing results revealed the software had a 14% positive predictive value. In other words, roughly 1 out of every 9 people who were flagged by the system were correctly identified as having ALS. This early detection method not only has implications in ALS, but in the larger populations of patients at risk of developing neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

This solution to the ALS diagnostic delay highlights two important points: it warns the public that they should never underestimate a pharmaceutical company’s ability to find customers, and it reveals that rare disease populations can benefit from pharmaceutical marketing budgets. Does this solution imply we should stop working on the systematic inefficiencies that allow patients with rare diseases to fall through the cracks? Absolutely not. Leslie Sands is living with ALS in San Luis Obispo. These are her recommendations for medical professionals everywhere:

    • A local specialist or primary care physician (PA’s and NP’s included) should urgently refer their patient to a university or a major hospital neurology center for evaluation when: they encounter a patient with unexplained slurred speech and have ruled out a stroke, traumatic brain injury, or other “obvious” conditions, and the patient’s labs are inconclusive with no obvious alerts.
    • The local doctor should not “suggest” that the patient seeing a neurologist associated with a university or major hospital may be a good idea; rather, the local doctor should emphasize the importance of seeing a qualified neurologist.
    • The local doctor or specialist should not be afraid to broach the possibility of a motor neuron disease (MND).

Leslie’s recommendations are echoed by ALS researchers who have collected data on patients who received a diagnosis far too delayed into their disease experience. One incredible ALS advocate, Sandy Morris, recommends that anyone who thinks they may have ALS symptoms, goes to a local emergency room and doesn’t leave until they receive a diagnosis. Hey, that’s one way to do it.

As with most complex problems, it is a combination of disciplines that need to collaboratively work towards a solution. While ALS patients encourage medical professionals to heighten their awareness of ALS, MT Pharma’s early detection algorithm will assist the doctors with the pattern recognition needed to correctly diagnose neurodegenerative diseases.

Related Articles:

Diagnostic Delays in ALS ‘Surprisingly Large’ and Need Not Be, Study Says

References

Martharan, Martin, Mathis, Stephane, Bonabaud, Sarah. (2020). Minimizing the Diagnostic Delay in Amyotrophic Lateral Sclerosis: The Role of Nonneurologist Practitioners. Neurology Research International. Volume 2020 Article ID 1473981, 8 pages.

Paganoni, S., Macklin, E. A., Lee, A., Murphy, A., Chang, J., Zipf, A., Cudkowicz, M., & Atassi, N. (2014). Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotrophic lateral sclerosis & frontotemporal degeneration, 15(5-6), 453–456.

ALS Podcasts

Stay Connected

The individuals and companies within the ALS Community are innovative and inspiring. Their collective actions illustrate how love and the fight for life motive real change. The following podcasts cover stories from people living with ALS, the science behind the disease, treatment options, caregiving experiences, and several other pertinent topics. These podcasts are a great way to stay informed while on the move. Enjoy! 

Many of these podcasts are available on Spotify, iTunes, YouTube and Soundcloud. The options for each podcast will become apparent once you visit the webpage by clicking on the above icons. 

The Political Front: National ALS Advocacy Conference

The National ALS Advocacy Conference

(May 26, 2020 – June 3, 2020)

The National ALS Advocacy Conference was virtual this year! The Martha Olson-Fernandez Foundation (MOFF) attended two days of the virtual event. Continue reading to get the inside scoop on the political interests of the ALS community.

What is The National ALS Advocacy Conference?

The National ALS Advocacy Conference is a week-long event in which patient advocacy groups lobby to raise disease awareness, present funding requests, and push policy initiatives that will support the ALS patient community. The event has a similar structure each year:

  • Daily conferences are held that discuss ALS research updates, ALS community needs, specific policy initiatives, and congressionally appointed fund requests for the year.
  • ALS patients and their families visit the offices of members of Congress to personally tell their stories and request support for the funding or policy initiatives that will benefit the ALS community.
Who were the main players in the “ALS community” during the 2020 ALS Advocacy Conference?
  • Muscular Dystrophy Association
  • I AM ALS
  • Team Gleason
  • ALS Association
  • Les Turner Foundation
  • American Academy of Neurology
  • National Health Council
  • National Organization for Rare Disorders
What were the main “asks” of the ALS community for FY 2021? (The requests that are placed in May 2020 pertain to the fiscal year (FY) 2021).

The ALS community is advocating for the following public policy priorities in FY 2021:

  • ALS Disability Insurance Access Act (S. 578/ H.R.1407): Request to waive 5-month waiting period for Social Security Disability Insurance (SSDI). This Act builds off the previous motion passed in 2000 that waived the 24-month Medicare waiting period. This is an urgent agenda item and currently has support from 61 senators and 238 representatives.
  • Expand Access to Home Infusion for Medicare Beneficiaries
  • Promising Pathway Act: Proposal to amendment to the Federal Food, Drug, and Cosmetic Act to establish a time-limited provisional approval pathway for certain drugs and regulated medical products.
  • Accelerating Access to Critical Therapies for ALS Act: Creates a pilot program to support expanded access programs. Will dedicate $75 million available in FY 2021 and FY 2022 toward this program.
  • Justice for ALS Veterans Act (S. 3091/H.R. 4748): This bill ensures that surviving spouses of veterans with ALS receive fair dependency and indemnity compensation.
  • Request for $40 million congressionally appointed dollars for the Department of Defense ALS Research Program.
  • Request for $10 million congressionally appointed dollars for the National ALS Registry.
  • Request for $44.7 billion congressionally appointed dollars for the National Institutes of Health (NIH).
What politicians are supporting the ALS cause?

The below list and commentaries provide a snapshot into the wide-ranging political support the ALS community has garnered.

  • Senator Mike Braun (Indiana) is championing the ALS Disability Insurance Access Act. In the virtual meeting on May 26th he stated: “I don’t think there is a good reason why this should not pass.”
  • Representative Peter Welch (Vermont) is supporting the ALS Disability Insurance Access Act. His commentary during the virtual meeting was, “Congress is a tough institution to move,” but the ALS community’s “long term advocacy is working.” He also stated that we currently have 238 supporters in the House, if we obtain 290, it “can be put on a consent calendar.” In lay terms, this would deem the Act as a topic that is not controversial and does not need to be discussed and can be accepted without a vote.
  • Representative Jason Crow (Colorado) affirmed that the ALS community “has a friend and an ally in Congress.” He is a prior Army Ranger whose wife’s cousin passed away from ALS.
  • Congressman Jeff Fortenberry (New England) introduced the Accelerating Access to Critical Therapies for ALS Act.
  • Congressman Mike Quigley (Illinois) co-sponsored the Accelerating Access to Critical Therapies for ALS Act.
How do the 2020 ALS community funding requests compare to historical asks?
  • To give you an idea of how much the ALS community’s political involvement has grown, in 1998 the government allotted $15 million dollars total to ALS research initiatives.
  • In FY 2020, the ALS community requested $20 million congressionally appointed dollars for the Department of Defense ALS Research Program. This was request was granted.
  • In FY 2020, the ALS community requested $10 million congressionally appointed dollars for the National ALS Registry/Biorepository development. This request was granted.
  • In FY 2020, the ALS community requested $105 congressionally appointed dollars for the NIH. The request was granted.
Conclusion

The 2020 National ALS Advocacy Conference was marked by monumental support and engagement from members of Congress. Despite the virtual platform, the ALS patient voices and actions could not be ignored. One key takeaway from the conference was the importance of forming coalitions with other patient groups. It is by unifying the patient voices, and combining them with the urges of doctors in their respective fields, that disease-community demands will be answered. This year, the American Heart Association and the American Lung Association formed key alliances with the ALS advocacy community on specific interests.

Thank you to all the parties involved in this monumental conference. Your efforts are saving lives. More information can be found on the ALSA, MDA and I AM ALS websites.

Sponsors

The main sponsors of the National ALS Advocacy Conference were the following pharmaceutical companies: Alexion, Amylyx, Biogen, biohaven pharmaceuticals, Genentech, Mitsubishi Tanabe Pharma America, and Soleo Health.

Healey ALS Platform Trial

What is the Healey Platform Trial?

  • An ALS clinical trial that tests 5 different therapies at 54 different trial sites across the United States. You can learn more about the structure and originality of  the trial here.

How many patients will be enrolled in the Healey Trial?

  • 160 patients will be enrolled per each of the five treatment arms.

What is the duration of the trial?

  • 24 weeks

When does the Healey Trial start?

  • There is not an exact date set yet. That being said, best estimates have the trial starting in May or June. People living with ALS are encouraged to contact trial sites near their residence as soon as possible. The enrollment will be competitive, meaning on a first come, first serve basis.

What phase clinical trial is this considered?

  • The stages of the therapies in the Healey Trial fall under the phase 2/3 trial or what the FDA considers a pivotal trial.

Please explain the expanded access element of the  trial.

  • Since the duration of the trial is not very long compared to other pivotal trials, the FDA encourages patients who would like to continue therapy usage after the trial is completed, to do so. This will allow researchers to monitor the long term safety of the therapy.
Curious about patient eligibility criteria? Click here and scroll to the bottom of the webpage.

Click on any of the company logos below to learn about the therapy they are contributing to the platform trial.

For more Healey Platform Trial info please click here for the MGH website

COVID-19 (SARS-CoV-2) Resources

Massachusetts General Hospital (MGH) has recently released incredibly useful webinars and Q&A sessions regarding living with ALS during this time of SARS-CoV-2. The link to their resource page is here. 

Follow this link to view SARS-CoV-2 resources synthesized by the ALS/MND Alliance. 

Click here to learn the latest ALS community updates on SARS-CoV-2 from I AM ALS.

We pray everyone stays safe and healthy during this time.

-The Board of the Martha Olson-Fernandez Foundation