Category Archives: ALS Research Events

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.

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.

8th Annual MOFF Golf Tournament: October 3, 2020

The 8th Annual MOFF Golf Tournament will take place at Cypress Ridge Golf Course October 3, 2020. Register today!

Click to Register
 
 

Click the image below to review this year’s sponsorship opportunities and fee structure.

COVID-19 Precautions

  • Individual tee time format instead of a shotgun start. Golfers will tee off every 8-9 minutes from 7:30 AM to 11:30 AM. As we get closer to the event, a MOFF representative will inform you of your tee time
  • 120 in-person golfer limit 
  • Virtual golf packages are available
  • A virtual silent auction will be held online and an in-person 50/50 raffle will take place at the course
  • Guest speakers will be featured on the MOFF golf tournament event website.
  • CA mask guidelines and social distancing regulations will be followed at the tournament
  • Temperatures will be taken 
  • All golfer merchandise will be handled with gloved hands 
  • Hand washing and hand sanitizer usage is highly encouraged 
  • Non-golfer visitors are discouraged (but we love you guys)
  • No awards ceremony this year. Winners will be announced on the golf tournament event website and social media channels. In addition, prizes will be distributed to 1st, 2nd, and 3rd place winners after the scores are determined. 
  • No Tapas Reception
  • Volunteers must sign up ahead of time. Please do so here

Golfers: Please bring your cell phones to the golf course. Check-in, auction activities, mulligan purchases, and course games will be conducted via your mobile devices. Thank you! 

2020 Virtual SLO ALS Walk

MOFF ALS Walk Team

Thank you to all those who helped us raise $1,825.00! Your generosity during this time of COVID-19 is what keeps the ALS patient care community going. 

In case you missed it, the MOFF team this year  walked for people living with ALS, the families of those who passed away from ALS, and we walked in memory of Katcho Achadjian.

Because ALS is fatal, our community is no stranger to loss and each year we invite more angels into our midst. This year, the MOFF team was dedicated to one of our SLO community leaders, Katcho Achadjian. He did not die from ALS, but his support of the ALS community was heartfelt and strong. We know he and Martha are getting into trouble wherever they may be 🙂 TO KATCHO! TO MARTHA! TO EACH OF US LIVING EACH DAY TO THE FULLEST. Stay strong.

Please view the MOFF Virtual ALS Walk Team video below. Check it out:

ALS Biomarker Panel at the Society for Brain Mapping and Therapeutics Conference

15–17 March 2019

SBMT 16th Annual Congress

Los Angeles Convention Center in LA

FLYER

The 16th Annual World Congress of SBMT brought together physicians, scientists, policy makers, funding agencies and industry to further the advances and applications in brain and spinal cord mapping and image guided therapies (operative and non-operative). The conference took place at the Los Angeles Convention Center.

The goal of the conference was to create a critical mass by introducing synergy amongst inter-disciplinary researchers to further understand the brain function and nervous system. It also served as a platform from which to develop interactions between many of the stakeholders who had extensive collaborations at national and international levels.

The conference provided the opportunity to be at the forefront of brain sciences, therapeutics in general and neural stem cells interventions in particular. It served as a strong platform for industry and biotech companies to interact with academia in frontiers of science in this field for translational initiatives involving diverse patient’s interest groups.

http://www.worldbrainmapping.org/Annual-Congress/

16th Annual Congress of Society for Brain Mapping promotional video – 2019 from Brain Mapping Foundation on Vimeo.


Topics & Speakers

Moderator: Mike Piscotty, ALS Cure

Biomarkers to aid diagnosis and monitor drug efficacy in clinical trials for ALS
Robert Bowser, Ph.D. The Barrow Neurological Institute

Biomarkers for CNS injury and disease
Kendall Van Keuren-Jensen , Ph.D. TGen

A data-driven approach links microglia to pathology and prognosis in ALS
Johnathan Cooper-Knock Ph.D. University of Sheffield, UK

Allosteric assembly machine modulators for ALS therapeutics
Vishwanath R Lingappa, M.D., Ph.D. Prosetta Sciences

Financing ALS biomarker discovery
Natalie Fernandez, 2019 MBA Candidate, The Martha Olson-Fernandez Foundation

The interdisciplinary nature of the SBMT conference allowed the ALS biomarker panel members to learn and collaborate with fellow industry members. The biomarker research topics were promising. Stay tuned for research article postings on the studies discussed.

Director Bobak Kalhor interviewed each of the panelist for an ALS media project. Bobak is director of “A Dying King- The Shah of Iran.” He recently lost his mother to ALS.

2019 California ALS Research Summit

Day 1 Takeaways: 

1. Whole genome sequencing (WGS) analysis projects are being undertaken by the following collaborative bodies: Track ALS, NeuroLincs, CABB, ALS Natural History, Answer ALS, NYGC ALS Consortium, and Target ALS. The data will be available to the public via the database ALSoD in early 2019.

2. There are several active stem cell trials being conducted in the U.S. by Braincell Therapeutics and also Avexis Pharma

3. Dr. Steve Finkbeiner from UCSF discussed machine learning in the context of ALS research. More specifically, he discussed how efficient and accurate the technology will be when it comes to exploring therapeutic targets and genetic patterns in neurodegenerative diseases.

4. There is currently a lot of research being done on the role of microglia, astrocytes, and macrophages in ALS. These research efforts attempt to understand the underlying pathology of the disease.

5. TDP43 was discovered to be present in all ALS models. It is now being looked at as a target that can be corrected with gene alteration.

Most of the top researchers in the ALS research world on the west coast were represented at the conference. The list below contains 5 ALS research pioneers. If you are interested in their research, each of them has many publications under their names.

* Leslie Thompson, PhD, UC Irvine
* Steve Finkbeiner, MD, PhD, UCSF
* Aaron Gitler MD, PhD, Stanford University
* Clive Svendsen MD, PhD, Cedars-Sinai Medical Center
* Dr. Richard Smith (CNS)

Day 2 Takeaways: 

1. The Lazarus Project was presented by Dr. Ranjan Gupta, MD from University of California Irvine. His research debunked the theory that motor function cannot be recovered after 6 months of de-innervation. His surgical procedures are truly miraculous. In some cases, he was able to execute nerve transfer surgeries to bring function back to limbs that had not been utilized for 6 years. Learn more about his research here.

2. Dr. Steve Finkbeiner’s lab revealed results from his high throughput microscopy project which targeted autophagy in ALS cells. Read more about his research here.

3. Mitsubishi Tanabe Pharma America, the company that makes Radicava, was represented by Dr. Stephen Apple, the senior medical director at the company. Dr. Apple discussed post market surveillance and their Phase 4 trial that they laid the foundations for. The Phase 4 trial plans to utilize biomarkers to detect the efficacy of the drug within ALS patients. Results from the study should be release in 2021.

4. New ALS targets were identified by Dr. Aileen Anderson from University of California Irvine. She studies spinal cord injuries and encouraged researchers to look into the autocrine signaling pathways in neuronal cells. More specifically, Dr. Anderson’s research explored neuronal stem cells to see if they had specific receptors that could be blocked. Her research found 5 novel receptors in neuronal stem cells that could be potential targets.

5. Routes of ALS drug administration were discussed in the context of antisense oligonucleotide therapies (ASOs) in order to answer the questions: How much virus is necessary, and where do you need to inject it in order to adequately cover the CNS? A new method of subpial drug administration (injection of the drug under the pia mater in the CNS) is being explored. Previously, intrathecal administration was the standard for ASO drug administration such as AVXS-10.

At the end of the day Ask the Experts took place in a separate building. At this panel, ALS patients and their families were able to discuss the most current scientific findings with the researchers themselves. Even though much progress has been made, the disconnect between the research world and the ALS patients was still noticeable.

ALS Leadership Summit Boston 2015

On November 15 2015, Martha Olson-Fernandez Foundation officers, Larry and Natalie Fernandez, attended the ALS Leadership Summit in Boston. The summit, hosted by ALS Therapy Development Institute (TDI), offered a wealth of knowledge on recent advancements in ALS research projects. The summit and featured speakers from Biogen, ALS TDI, The Forbes Norris ALS/MDA Clinic in San Francisco, and the Harvard School of Public Health. The attendees included investment companies, top researchers in the NMD/ALS field, pharmaceutical company representatives, as well as ALS patients and their families. The energy in the conference room at the Hyatt was charged by powerful minds, and a frustrated search for answers to such a complex disease pathology. The element of time was what everyone felt short on.

The takeaway from the conference was that ALS is not an untreatable disease, but an underfunded one. Recent research has surfaced many new findings about the disease and the role of the immune system in the final stages of the disease, but due to the nuanced subjectivity and spectral nature of ALS, researchers are still racing time to find treatments.

Overall, the summit centered around several key topics:
1. The importance of utilizing biomarkers to track pathogenesis and drug efficacy in ALS patients.
2. The methodology behind initiating, and executing preclinical research projects at ALS TDI
3. The structure and function of the Precision Care Program at ALS TDI
4. The discovery of the role of the immune system in the later stages of ALS and how this immobilizing stage of ALS can potentially be slowed and prevented with AT-1501.
5. Biogen’s discussion of new ways to visualize how effective intrathecal drug delivery is at getting the drug molecules passed the blood brain barrier and into the Central Nervous System (CNS).

The ALS TDI Leadership Summit hosted an awards ceremony during which it recognized several courageous people dedicated to fighting ALS. The 2015 Leadership Award winners are listed below:
Award: Stephen Heywood Patients Today Award. Recipient: US Navy LT. Commander (RET.) Matt Bellina (Holland, PA)
Award: Stephen Milne Adventurous Spirit Award. Recipient: Sarah Coglianese (San Fransisco, CA)
Award: Mary Lou Krauseneck Courage & Love Award. Recipient: Bobby Forster (Newport, RI)
Award: Fran Delaney Challenge & Respect Award. Recipient: Beth Hebron (Maplewood, NJ)
Award: Stephen Mile Adventurous Spirit Award. Recipient: Maureen Ramirez and Team Godfather Charitable Foundation
Award: Stephen Heywood Patients Today Award. Recipient: Jay Smith (Austin, TX)

 

Thank you to ALS TDI for the informative and well executed leadership summit.