A COVID-19 Research Update

Dear Friends,

Project ALS is acutely aware of the unimaginable circumstances that Americans and people around the world are now facing. Our hearts, souls, and minds are heavy with the dire situation that ALS patients, family members, and loved ones are facing every second of every day. COVID-19 is a stark reminder of what people with ALS must endure every day.

Project ALS has faced adversity before, but this is a particularly tough blow. Before COVID-19 struck, we were well on our way to reaching our goal of moving our first-ever lead drug candidate, Prosetin, to ALS patients by summer 2020. The FDA-required safety studies at Charles River Laboratories and the manufacturing program at Patheon were underway and on target. We were working every day with our pre-clinical and clinical research partners at Columbia University, and our team of expert consultants, to finalize our submission to the FDA and confirm plans for our Phase 1 clinical trial. We were churning on all cylinders with fundraisers planned throughout quarters two and three to cover our research expenses planned and unforeseen.

Like everyone else, COVID-19 has thrown us into uncharted territory. All scheduled plans to raise revenue to get Prosetin to patients have been upended: our physical fundraisers and community events have been cancelled through July, and online fundraising has slowed. Academic laboratory research has been mandated to halt indefinitely, and we do not know when clinical trial initiation will be possible. We are working every day to keep things on track but fear we will have to veer from our original projections.

We are essentially at war, and are keenly aware of the hardships that each and every member of our community is facing—but to keep Prosetin moving forward, we need your help. If you are able to, please make a donation or create an online fundraising page here, and share this message with your community.

Next Tuesday, April 7th, at 1pm EST, join our team live on Facebook for a candid discussion of the challenges facing Project ALS research at this critical time. Now more than ever, we need to hear from you.

Love,
Meredith, Valerie, Erin, & the Project ALS team

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Medidata Institute and Project ALS Launch Partnership to Accelerate New Treatment Strategies

Project ALS is excited to launch a new research partnership with the Medidata Institute targeting new, actionable insights into ALS disease progression and subtypes.
Medidata develops world-leading solutions for the life science industry, with digital platforms spanning clinical development, commercialization, and real-world data. Through this collaboration with Project ALS, Medidata will turn its Rave Omics biomarker discovery platform, as well as its considerable manpower and expertise, toward identifying new biomarkers and patient subsets of ALS.

For Project ALS, this collaboration comes at a pivotal time. We now know of more than 60 genes that are involved in some way in ALS…but we are only beginning to understand how these genetic mutations cause or contribute to the disease. We realize that people who have different subtypes of ALS are likely to respond differently to potential treatments, but we don’t have enough information to predict this response before lengthy clinical trials. Critically, we want to design better clinical trials for Prosetin and future drug candidates that will emerge from THE CORE…and with Medidata, we have a real chance of moving the field toward more humane, informative clinical programs.

First up in the partnership? A pilot study that will feed data from a 2012 ALS proteomics study and matched clinical data from the same patients into the Rave Omics platform.  The goal being to figure out whether specific protein signatures impact how quickly a person’s ALS progresses. Project ALS thanks SomaLogic and the ALS Living Library at Mass General for providing the raw data for this pilot study.

Read the press release from Medidata here.

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Valentine for a Pioneer

Jaci and her horse Bud,  March 2019

Jaci is blazing a path that hopefully will not just cure her but set a course of treatment for countless others.” – Lori Hermstad, mother.

February 14th is a significant day for the Hermstad family. On this day in 2011, Alex Hermstad lost her battle with ALS at age 17. On this same day exactly eight years later, Alex’s twin Jaci was diagnosed with the same rare, aggressive form of ALS that took her sister. Jaci got to work building a dream team captained by drug regulatory expert Dr. Lauren E. Black. The team included Jaci’s family, community, Project ALS, Drs. Neil Shneider and Robert Brown, Charles River Laboratories, and the FDA. Now, a year later, Jaci has received eleven doses of jacifusen, a new type of gene therapy named just for her. In this one year, Jaci has become a portrait of courage for the ALS community and beyond. Thanks to her advocacy, jacifusen was born, and will now be tried by others with the same genetic form of ALS.

In October 2019 at the Project ALS fall gala, Alex and Jaci’s mother Lori spoke of being overcome with “a sense of hope and faith that comes from [her] twin daughters: one who fought tirelessly for six years to lay the groundwork for future treatments, and the other who we hope fulfills the destiny of her sister’s love and sacrifice.” For the Hermstads, Valentine’s Day is not just another holiday – it’s a constant, indelible reminder of the sisters’ immense love and sacrifice. Today we honor Alex and Jaci and reflect on the significance of their story. They have fearlessly and fervently paved the way for so many others. They are making history.

Learn more about the collaboration between The ALS Association and Project ALS to fund an expanded access program for jacifusen at Columbia University.

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Project ALS Introduces Prosetin

What’s Prosetin?

If you’ve been following Project ALS, you have probably heard us mention PHB, our working name for The Core’s first drug candidate-in-development. Now, we are proud to announce the final version of PHB—the real thing—a fully optimized, comprehensively tested drug for ALS called prosetin.

(more…)

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Ai Yamamoto Joins Research Advisory Board

Project ALS is thrilled to welcome Dr. Ai Yamamoto to the Research Advisory Board and recognizes her leadership as she is joining our decision-making body. Dr. Yamamoto is the Associate Professor of Neurology and Pathology and Cell Biology at Columbia University and is a foremost expert on protein clearing, or autophagy, in neurodegeneration, particularly in Huntington’s and Parkinson’s diseases.

Project ALS has partnered with Dr. Yamamoto for about three years, as we strive to identify the role of autophagy in Huntington’s, ALS, and related diseases. We look forward to seeing where her leadership will take us.

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Project ALS and Columbia University Announce the Project ALS Therapeutics Core at Columbia

Columbia University and Project ALS today announced the Project ALS Therapeutics Core at Columbia, a 3-year, $6.3M initiative toward the first meaningful therapies for ALS. The Core is the world’s first and only partnership between a world-class academic institution and a leading nonprofit organization dedicated to a full-spectrum approach to ALS drug development, preclinical evaluation, and human clinical trials.

The goal is better clinical trials—and the first effective treatments for people with ALS, a uniformly fatal neurodegenerative disease closely related to Alzheimer’s, Parkinson’s, and Huntington’s diseases. Already, the Core has yielded a novel drug, and evaluated dozens of commercial compounds in partnership with pharmaceutical companies.

The Core begins and ends with ALS patients—it will utilize patient blood samples toward drug screening, biomarker discovery, and genetics studies, and deliver better therapeutic options back to the clinic, to patients who have participated at the start of the process.

“For the first time, ALS patients can directly participate in research that will move us toward therapies that actually work,” said Neil Shneider, MD, PhD, Director of the Eleanor and Lou Gehrig ALS Center at Columbia. “The Core provides an immensely exciting opportunity to capitalize on decades of ALS advances and translate them into meaningful treatments now.”

Read the full press release here, and stay tuned for more information about the Core. In the meantime, please contact [email protected] with any questions about this exciting new initiative.

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New ALS Drug Screening Platform Identified; Leads to Early-Stage Drugs of Promise

Q&A with Project ALS Researcher Dr. Sebastian Thams, Karolinska Institute, on His Recent Discovery, Published in Molecular Therapy

Can you describe your discovery that was recently published in Molecular Therapy?

In our recent paper, we present a new screening platform, in which we elicit neurodegeneration by exposing ALS motor neurons to a biological stressor. We used this assay to screen for neuroprotective compounds reversing ALS-associated cell stress. We identified two groups of promising compounds, which increased motor neuron survival in mouse and human cultures, and delayed loss of muscle nerve endings in ALS mice. These compounds included protein kinase inhibitors and a bile acid. Altogether, our results have now enabled us to start the development of completely new drugs for ALS.

How does this discovery add to the field of ALS drug testing?

Our study demonstrates that stem cell-based screening models are valuable tools for swift and robust evaluation of potential drug candidates. As a proof-of-concept, we showed neuroprotective drug effects in mouse and human cell cultures, as well as in muscles from ALS mice, thereby strengthening the notion that important results from cells in cultures can be applied to ALS patients in the future.

How does this bring us closer to treatments for patients? 

We have now identified promising compounds that reverse disease-related processes in motor neurons. While most of these compounds are not suitable for direct testing in patients in their present form, they possess important neuroprotective properties, which we are now taking advantage of. The compounds are in the process of refinement and modification to be more suitable for treatment in patients. We are optimistic that the compounds can soon be ready for testing in ALS patients.

How has Project ALS affected your career?

Project ALS has created a stimulating academic environment for cutting edge translational stem cell research, which I had the great opportunity to be a part of during my time at Columbia University. My experience at the Project ALS laboratory provided me with essential tools that I now use in my own laboratory. The nurturing setting fostered an invaluable international network, which I benefit from in current collaborations.

What did you focus on in your early work with Project ALS? 

I was particularly interested in setting up new platforms for drug screening using stem cell-derived neurons. I focused specifically on the intrinsic properties of motor neurons that render them susceptible to neurodegeneration. My outstanding goal was to gain new insights into motor neuron vulnerability, and subsequently, use this knowledge to design new therapies for ALS.

What else have you been working on recently? 

I presently divide my time between working as a physician and a scientist at the Department of Neurology, Karolinska University Hospital in Stockholm, Sweden. I am involved in both clinical trials for new ALS treatments and basic research projects related to cell stress mechanisms in ALS. Time management is a struggle when you split your attention, but I have the great opportunity to work on projects ranging from cells to patients. My goal is to improve the clinical management for ALS patients, and hopefully contribute to the development of more potent treatments for the disease.

Read the published study here.

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Kirchhoff Family Fellow Proposes New Therapeutic Strategy in ALS

Joesph Klim, PhD, a Kirchhoff Family Fellow at the Lab of Kevin Eggan, PhD at Harvard University has discovered that restoring expression of the gene Stathmin2, or STMN2, rescues motor neuron degeneration, a hallmark of ALS. Findings were published on January 14th, 2019 in Nature Neuroscience.

Dr. Klim has spent the last three years studying TDP-43, a protein previously known the be involved in ALS. His recent discovery shows that TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. So when TDP-43 is perturbed, STMN2 is diminished and motor neurons suffer as a consequence, causing the body to lose the ability to move. Klim used patient stem cell models of ALS, as well as spinal cord samples donated by dozens of ALS patients, to show that boosting STMN2 could slow motor neuron degeneration in patients, regardless of their cause of ALS.

Said Klim, “Our work highlights STMN2 as a credible drug target for ALS and a potential new biomarker.”

Named in honor of former Project ALS board member and inspiration Tom Kirchhoff who passed away from ALS in 2015, the Tom Kirchhoff Family Post-Doctoral Fellowship at Project ALS is given to promising young scientists already making a difference in ALS research. “After meeting the Kirchhoff family”, said Klim, “I was inspired by their strength and courage to pursue ALS treatments as Tom battled this devastating disease and by their resilience and determination to continue this fight after his passing. As the Tom Kirchhoff Family Postdoctoral Fellow, I had the freedom to pursue this complicated and long-term project, and I was bolstered in my efforts by the strong Kirchhoff family spirit.”

Klim’s breakthrough demonstrates the power and interconnectedness of those who are affected by the disease, and those researching it – an important tenet of the Project ALS mission. Said Dr. Kevin Eggan, “These experiments…point towards a clear path for testing whether repairing STMN2 in our friends and family can slow or stop their disease.”

Read more about the study on the Harvard Department of Stem Cell and Regenerative Biology’s website.

(Photo: Dr. Kevin Eggan discusses Klim’s findings at the Project ALS gala onstage with the Kirchhoff family)

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Doctors Track Relatives of ALS Patients for Clues on Disease: Project ALS and Columbia Launch ALS Families Project; Goal of Early Detection and Treatment

Project ALS and Columbia University’s Eleanor and Lou Gehrig ALS Center have opened the ALS Families Project to study relatives of ALS patients who carry genetic mutations associated with the disease.

“Studying the relatives of these patients provides the opportunity to understand the earliest steps in the onset of ALS, which may occur months or even years before obvious symptoms appear,” says Neil Shneider, MD, PhD, who directs the Families Project. “By closely following relatives who carry the same mutation,” Shneider says, “we hope to develop markers of ALS that can guide our efforts to intervene early in the course of the disease.”

“Project ALS recognized an unmet need to follow and examine asymptomatic family members of ALS patients throughout their lives as they, more than any lab model or subject, have great potential to unlock mysteries of the disease, for familial, but also sporadic cases as well,” said Valerie Estess, Project ALS director of research. “We are very excited to partner with Columbia on this program and plan to expand it significantly.”

The program has already enrolled more than 12 pre-symptomatic gene carriers from New York City and elsewhere. Participants will come to Columbia once or twice a year for examination and testing.

Read more about the Families Project and how it will bring us closer to treatments on Columbia Medical Center’s website. Contact [email protected] or 212-420-7382 if you or someone you know would like to participate.

(Photo: Dr. Neil Shneider meets with participants of the Families Project)

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Autophagy Team Update

Last year, we announced the formation of a six-lab collaboration at the direction of Project ALS to focus on the cell process known as autophagy, or a cell’s ability to clear itself of unwanted proteins. Autophagy Team director, Tom Maniatis, and his laboratory, have led efforts to identify what goes wrong with autophagy in ALS, and how we might fix it. The original team includes leading labs from Columbia, Cornell, University of California San Francisco, and the New York Genome Center. One major focus of this year’s work has been the gene TBK-1, a player in the cell clearing process. Project ALS and Dr. Maniatis recently added collaborators from the New York Structural Biology Center to generate helpful 3-D models of TBK-1 and other autophagy-related genes and targets for use by the team. More recently, Project ALS recruited the eminent Dr. Erika Holzbauer, from the University of Pennsylvania, who is focused on the dynamics of the active transport of cargoes—unwanted protein aggregates—in ALS neurons.

(photo: Drs. Steven Altschuler and Lani Wu of UCSF, researchers on the Project ALS Autophagy Team)

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