Projects Funded 2022

Table of Contents

2022 ALS Canada-Brain Canada Discovery Grant Program

Can this routine and inexpensive procedure have a neuroprotective effect in ALS?

Remote ischemic preconditioning treatment in amyotrophic lateral sclerosis

$125,000 awarded to Dr. Carlos Rodrigo Camara-Lemarroy, University of Calgary, in collaboration with Dr. Minh Dang Nguyen, University of Calgary, and Dr. Deepak Kaushik, Memorial University of Newfoundland

Remote ischemic preconditioning (REIP) is an experimental medical procedure that has been tested as a treatment in cases of heart attack and stroke to try to reduce the severity of injury. REIP involves the use of a blood-pressure cuff to temporarily cut-off blood flow to a limb resulting in ischemia (lack of oxygen) that is often repeated multiple times as part of the procedure.

This “conditioning” activates the body’s natural protective mechanisms against tissue injury and previous studies have shown that REIP in one organ or limb can lead to protection in other areas of the body. The practice of REIP is thought to modulate inflammation, reduce oxidative stress, activate neurotrophic factors (substances thought to support nerve cell repair), and regulate the expression of genes that promote tissue repair.

With this grant, Dr. Camara-Lemarroy and his team will explore the potential of REIP as a treatment for ALS. Researchers will investigate the effects of daily REIP prior to symptom onset in a mouse model of ALS and monitor the effects on motor function, motor neuron degeneration, neuroinflammation and lifespan compared to a control group. The team will also seek to identify the cellular mechanisms that contribute to the effects of REIP, with the aim to uncover specific pathways that may increase the expression of neurotrophic factors and promote motor neuron survival.

If found to be effective, REIP would need to be tested in human clinical trials to confirm the benefits, however, the simplicity of this medical procedure suggest it could easily be translated into the clinic. Additionally, exploration of the underlying mechanisms that play a role in the beneficial effects of REIP, as proposed in this study, may help to uncover new treatment targets for drug discovery.

Could this new mouse model help to understand the potential role of retroviruses in ALS and lead to new treatments?

DNA damage driven motor disturbance in ALS: An ERVK integrase transgenic mouse model

$125,000 awarded to Dr. Renée Douville, University of Winnipeg, in collaboration with Dr. Jody Haigh, University of Manitoba, and Dr. Domenico Di Curzio, St. Boniface Hospital Albrechtsen Research Centre

Within our genome (the complete set of DNA present in a person) are pieces of viral DNA passed along from our ancestors. These human endogenous retroviruses (HERVs) have been termed “fossil viruses” as they are the footprints of previous viral infections our ancestors experienced and have passed down through generations. It is estimated that HERVs make up from one to eight per cent of the human genome.

For the most part, HERVs are thought to be relatively innocuous, lying dormant within our cells. However, it is hypothesized that some of these HERVs have the potential to produce viral products and therefore can become active. This has led researchers to propose a role for HERVs in certain autoimmune diseases, cancers, and neurological disorders such as multiple sclerosis (MS) and ALS.

Dr. Douville has previously shown that expression of a specific HERV protein, called ERVK, may promote inflammation and motor neuron degeneration in a subset of ALS cases. However, the exact mechanism through which this occurs remains unknown.

With this grant, Dr. Douville and team will develop and validate a mouse model representative of ERVK-driven neurodegeneration. This new model will allow researchers to test on a cellular level how expression of ERVK may influence a variety of pathological mechanisms, including DNA damage, neuroinflammation, TDP-43 dysfunction and neuronal loss. The mice will also be monitored to look for changes in motor function over time.

Establishing this mouse model could lay the foundation for future drug screening studies aimed at identifying promising new antiviral drugs to test in clinical trials. There are already multiple ongoing clinical trials evaluating the effects of antiviral drugs in ALS, however, these studies are often based on Human Immunodeficiency Virus (HIV) treatment strategies. Ultimately, the team aims to use this mouse model to develop a more targeted approach specific to ALS.

Could this new 3D cell culture model help researchers better predict disease progression in ALS?

Modeling ALS progression by applying neuroinformatics to a novel in vitro human 3D tri-culture model of the disease

$125,000 awarded to Dr.Thomas M. Durcan, The Neuro (Montreal Neurological Institute-Hospital), McGill University, in collaboration with Dr. Yasser Iturria-Medina, McGill University

A growing body of evidence suggests that other cell types within the brain influence motor neuron health and survival. Microglia, for example, are the immune cells of the brain that usually play a protective role, but if altered, can become toxic to motor neurons. Astrocytes are another type of specialized support cell within the brain with a wide range of functions, and when these cells don’t function properly the health of motor neurons suffer.

To properly model ALS in the lab, understanding the complex interplay between these various cell types is key. With this grant, Dr. Durcan will create a three-dimensional (3D) model of ALS, called a spheroid, using induced pluripotent stem cells (iPSCs). iPSCs have become an invaluable tool when studying neurodegenerative disease as these cells retain the genetic information of the patient who donated them and can be transformed into motor neurons or any other cell type, such as microglia or astrocytes.

The spheroids developed will represent a variety of familial forms of ALS (SOD1, TARDBP and C9ORF72), as well as sporadic ALS and healthy controls. These models will be analyzed using different assays to study the microglia-astrocyte interplay in ALS, its influence on neuronal health, and how this differs between the various forms. In collaboration with Dr. Iturria-Medina, an expert in neuroinformatics (a research field that focuses on analyzing neuroscience data through computational models), the data obtained will also be used to develop prediction models that may be able to uncover different patterns of progression for different forms of ALS.

By combining an advanced 3D model of ALS and powerful neuroinformatics, the team hopes to gain a better understanding of how neuroinflammation may contribute to ALS, and whether progression may differ depending on the type of ALS being studied. In the future, the team plans to build upon this work to incorporate other cell types into the spheroids and ultimately use these models to study treatment response for new ALS therapies.

Could protecting the axon represent a promising treatment strategy for ALS?

Axonal degeneration as a therapeutic target for ALS

$300,000, in partnership with Dr. Jean-Pierre Canuel Fund – SLA Québec and Brain Canada, awarded to Dr.Alex Parker, Centre de recherche du CHUM at Université de Montreal, in collaboration with Dr. Gary Armstrong, McGill University

Motor neurons are the living wires within our bodies that carry electrical signals from our brain to our muscles. What makes motor neurons unique compared to other cell types is their shape. Motor neurons have a long cable called the axon that carries electrical impulses through the cell to either the next motor neuron in the chain or a muscle, causing it to contract.

The axon is a dynamic structure, changing in response to external stimuli leading to growth (regeneration), branching, or retraction (degeneration). Damage to the axon has been observed in a variety of neurodegenerative diseases, including ALS. Some suggest that axonal degeneration may be one of the first steps in the onset of ALS and previous studies have shown that damage to the axon can cause symptoms even when the cell body of the motor neuron is intact.

Dr. Parker and his team hypothesized that stimulation of specific genetic pathways known to promote axon regeneration may help to delay the onset or slow the progression of ALS. In Dr. Parker’s lab, they use small worms, called C. elegans, to model ALS. These worms are only a millimetre long, but since they have short lifespans and share 60 per cent of their genetic makeup with humans, they are ideal animals to use in research.

In this study, Dr. Parker and team will build upon previous foundational work within the lab. First the team will identify specific genetic pathways shown to supress axon degeneration. Then they will test various small molecule inhibitors of proteins linked to these pathways to assess their potential as future treatment options for ALS. Finally, in collaboration with Dr. Armstrong, they will validate these findings in zebrafish and human iPSC ALS models. The results from this study will help to reveal new targets for therapeutic development with the ultimate goal of moving promising candidates into clinical testing.

Could the study of neuromuscular junction proteins aid in the development of essential biomarkers?

Neuromuscular proteins as potential biomarkers in ALS

$300,000 awarded to Dr.Richard Robitaille, Université de Montréal, in collaboration with Dr. Danielle Arbour, Dr. Roberta Piovesana, Université de Montréal, and Dr. Robert Bowser, Barrow Neurological Institute

Biomarkers are biological measures that can be used to understand the real-time processes happening in the body. Validated biomarkers are urgently needed to help clinicians diagnose ALS, track progression of the disease and measure response to therapies. Dr. Robitaille and team believe that proteins related to the neuromuscular junction (NMJ) may help to fill this need.

The NMJ is the place where motor neurons connect to muscle fibers. This junction allows for signals from the brain to pass to muscles. Many researchers believe that one of the earliest events in ALS is the disconnection of motor neurons from muscles at the NMJ. As this disconnection occurs, NMJ-related proteins can be released into the bloodstream. With this grant, Dr. Robitaille will investigate whether any of these proteins could serve as a reliable biomarker for ALS.

Previous studies have revealed that some muscle types are more resistant to NMJ disconnection than others. For example, in both humans and ALS mouse models, the eye muscles preserve these connections longer, which is why many assistive devices for ALS use eye movements for control. By comparing resistant and vulnerable muscle types in a mouse model of ALS, Dr. Robitaille identified a set of candidate biomarkers reflective of NMJ dysfunction.

Here, the aim is to validate these candidate proteins as diagnostic and/or prognostic (progression) biomarkers using human fluid (plasma) samples. Additionally, the team will explore whether candidate biomarkers can be used to track treatment response in mice treated with an experimental therapy called darifenacin. Preclinical work showed that treatment with darifenacin slowed weight loss, maintained motor function, and increased life span in ALS mice, and as a result Dr. Robitaille recently received support through the ALS Association’s Clinical Trials Awards Program to move darifenacin into a human clinical trial in 2023.

Validation of these potential biomarkers could enhance diagnostic accuracy, lead to earlier diagnosis, and provide more accurate markers of ALS progression. Moreover, this work could help to confirm the target and selectivity of the experimental treatment darifenacin, which are important steps in the drug development pathway.

Could improving the mechanisms of toxic protein disposal in motor neurons become a future treatment strategy?

Elucidating the basis for ubiquitination of misfolded ALS proteins by E3 ligase enzymes

$125,000 awarded to Dr.Gary S. Shaw, Western University, in collaboration with Dr. Martin Duennwald, Western University, and Dr. Elizabeth Meiering, University of Waterloo

Proteins are often referred to as the workhorses of the cell as they complete nearly all cellular functions required to sustain life. To perform these tasks correctly, proteins must fold into the correct 3D shape. If they take on the wrong shape, a process referred to as protein misfolding, they can stick together and form aggregates (or clumps) within the cell. A hallmark feature in both sporadic and familial forms of ALS is the presence of misfolded proteins, such as SOD1, TDP-43 and FUS, within motor neurons.

The body has natural mechanisms to promote the proper refolding, or degradation and removal of misfolded proteins before they can negatively impact neuronal health. One such mechanism is called the ubiquitin-proteasome system, which involves the labelling of a misfolded protein with a small tag called ubiquitin which serves as a signal to the cell to degrade the protein.

Dr. Shaw and his team hypothesize that problems in the ubiquitin-proteasome system may play a role in ALS. With this award, they will study three proteins (Dorfin, Parkin and NEDL1) that all have an early role in the selective tagging of folded vs. misfolded forms of ALS-associated proteins.

Using structural and enzymatic experiments, the team hopes to uncover the mechanisms by which the activity of Dorfin is regulated, and how this knowledge could be used to amplify its activity towards misfolded proteins specifically. The team will also investigate the sites where ubiquitin tags are placed on SOD1, TDP-43 and FUS, and whether the types of tags or the ability to place the tags differ between misfolded and folded forms.

The knowledge gained from this study has the potential to accelerate the development of small molecule therapeutics aimed at more effectively clearing from cells toxic protein clumps associated with ALS. This approach has shown promise in other disease areas such as Parkinson’s disease and certain types of prostate and breast cancers.

Can computational methods aid in the design of key antibodies for the diagnosis and treatment of ALS?

Rational targeting of FUS and TDP-43 protein assemblies for diagnostics and treatment of ALS

$125,000 awarded to Dr.Maria Stepanova, in collaboration with Dr. Holger Wille, University of Alberta

A protein is said to have prion-like behaviour when it fulfills two major criteria: first, it must be able to cause other normally-folded proteins to change their shape and adopt a toxic shape. Second, it must trigger a chain reaction, moving from cell to cell creating a domino effect of toxic protein misfolding and aggregation that spreads throughout the nervous system. Well-known prion diseases include scrapie in sheep, mad cow disease in cattle, and Creutzfeldt-Jakob disease in humans.

Some researchers believe that a prion-like mechanism may contribute to disease progression in ALS and that the size and shape of the aggregates differ depending on the protein involved or even the specific mutation within a particular protein. The difference in the aggregates formed could help to explain the varying symptoms observed in people living with ALS.

With this grant, Dr. Stepanova will use computational methods to predict the structure of abnormal protein aggregates formed by two ALS-linked proteins, TDP-43 and FUS. Results from the sophisticated computational analyses will provide researchers with the framework to design antibodies that can target these aggregates and hopefully slow or stop the toxic domino effect.

Antibodies are proteins naturally produced by the immune system to protect the body against foreign invaders like bacteria and viruses. Antibodies, however, are also commonly used as a tool in research because they can be designed to bind to specific proteins within the body making them ideal candidates for detecting biomarkers or even as treatments for various diseases.

In collaboration with Dr. Wille, the team will create antibodies capable of specifically binding to the toxic protein assemblies identified in the initial computational studies. To validate whether these are relevant in a human context, the antibodies will be tested in brain tissue samples donated from ALS patients. If the antibodies successfully bind, this will suggest that the predicted protein aggregate structures are involved in ALS diseases processes and reveal new targets for future drug development. Additionally, the already developed antibodies could be examined further to assess their potential as tools to detect diagnostic biomarkers or even as treatment options for ALS.

What role does its sister protein play when restoring G3BP1 levels as a potential ALS treatment strategy?

Deepening our understanding of G3BP1 and its paralog G3BP2 to facilitate accurate therapeutic development for ALS/FTD

$125,000 awarded to Dr. Christine Vande Velde, Centre de recherche du CHUM at Université de Montreal, in collaboration with Dr. Marlene Oeffinger, Institut de recherches cliniques de Montréal (IRCM)

TDP-43 is a protein that behaves abnormally in the motor neurons of 97 per cent of people with ALS. It is usually found in the nucleus, but in people with ALS, it becomes trapped outside in the cytoplasm where it forms aggregates. Previous work in the Vande Velde lab showed that the mislocalization of TDP-43 to the cytoplasm results in decreased levels of another protein, called G3BP1.

G3BP1 is an essential protein for the formation of stress granules, which are protective structures that healthy cells make when they are exposed to environmental stress. Stress granules protect vulnerable RNA (molecules that translate genetic instructions and oversee protein production) from becoming damaged.

It remains unclear whether the role of G3BP1 in stress granule dynamics is the main contributor to it’s influence on motor neuron health, or whether it has additional functions in key cellular pathways. Preliminary work suggests a role for G3BP1 in additional pathways, as studies examining its sister protein G3BP2, which has a similar function in stress granule dynamics, reveal that when G3BP1 levels are reduced G3BP2 cannot fully compensate for the loss.

With this award, Dr. Vande Velde seeks to understand the function of G3BP1 in a more holistic way. The team will define and compare the protein interaction network for both G3BP1 and G3BP2 in neurons. They will also examine the role both proteins play in RNA degradation within cells and how this influences ALS disease processes. Finally, they will explore whether a unique, recently understood biology in ALS, called cryptic exon inclusion, is responsible, at least in part, for the loss of G3BP1 at the RNA level.

Ultimately, the results from this study will help researchers more fully understand the wide array of cellular functions G3BP1 is involved in, and how these differ compared to its sister protein G3BP2. The proposal builds on prior foundational work and will influence ongoing studies aimed at restoring G3BP1 levels as a treatment strategy for ALS.

Will this new way of looking at certain protective proteins better explain their role in ALS?

The impact of ALS disease variants on regulation of heat shock protein life cycles – Implications for neuronal proteostasis

$125,000 awarded to Dr. Maria Vera Ugalde, in collaboration with Dr. Heather D. Durham, McGill University

In ALS and many other neurodegenerative diseases, one of the defining characteristics is that proteins can become misfolded and clump together, potentially damaging nerve cells. When a healthy body responds to this type of stress, protective mechanisms increase the production of heat shock proteins (HSPs) that work like guardians inside cells helping to refold proteins so they can work again, or, if that doesn’t work, ensuring that they are destroyed.

It’s suggested in ALS that HSPs are unable to keep up with misbehaving proteins and therefore can no longer protect against trouble at the cellular level. As a treatment strategy, researchers have previously identified drugs that aim to boost the production of HSPs, however, so far, their effectiveness has been limited.

Dr. Vera Ugalde hypothesized that the expression of ALS-linked proteins within cells may interfere with the regulation of HSPs which ultimately could compromise the efficiency of HSP-boosting therapies. With this grant, Dr. Vera Ugalde will use cutting-edge single-molecule tools to study the impact of three ALS-associated genes (FUS, TARDBP, and SOD1) on the life cycle of HSPs in cell cultures, ALS mouse models and donated human tissue samples. The team will also analyze how the presence of ALS-linked proteins impact the activity of known HSP-boosting drugs and related disease mechanisms.

The results from this study will provide researchers with a more comprehensive understanding of the HSP life cycle in an ALS context, which may shed a light on why previous HSP-boosting drugs did not meet expectations and provide a framework for optimizing these types of treatments in the future.

2022 ALS Canada-Brain Canada Career Transition Award

A new way to look at the most common genetic form of ALS

Loss of C9orf72 disrupts nucleoporins and contributes to TDP-43 mislocalization

$250,000 awarded to Dr. Philip McGoldrick at the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto

Mutations in the C9ORF72 gene are the most common genetic cause of ALS. These mutations are unique in that unlike most other ALS-linked genes, where there is often a mistake in a single piece of DNA, C9ORF72 mutations involve a section of DNA that is abnormally repeated, often hundreds or even thousands of times. These repeat mutations result in less of the normal C9ORF72 protein being produced within cells, which is suggested to impair its ability to do its normal job.

Growing evidence also points to a significant involvement of C9OF72 mutations in the disruption of nucleocytoplasmic transport (NCT) within cells. NCT involves the exchange of substances between two important compartments of the cell, the nucleus and cytoplasm, and is crucial to cell survival. The exact mechanism for this disruption, however, is still unknown.

With this award, Dr. Philip McGoldrick will explore the link between a loss of normal C9ORF72 function and nucleocytoplasmic transport, and whether dysfunction in this system contributes to the abnormal behaviour of another ALS-linked protein, called TDP-43, which is found to be mislocalized from the nucleus to the cytoplasm in 97% of all ALS cases. To date, most of the connections made between C9ORF72 mutations and NCT have related to a different mechanism, making Dr. McGoldrick’s work unique in the field.

Expanding on previous work, Dr. McGoldrick will study changes in the biology of nuclear pore complexes (NPCs), the large protein complexes responsible for moving substances between the nucleus and cytoplasm, as well as the downstream effects of these changes on important cellular processes such as the stress response and protein homeostasis. He will also evaluate whether loss of C9ORF72 in combination with normal ageing processes contributes to neuronal degeneration in human cell models.

Ultimately, this work will help researchers to better understand how an important cellular process may be disrupted in the early stages of ALS. Understanding why these changes occur and what the downstream effects are will no doubt be key to future therapeutic development. Dr. McGoldrick hopes to grow this project into a career based on developing new laboratory models and treatments for all forms of ALS.

2022 ALS Canada Trainee Awards

Doctoral Awards

Does this newly discovered tag on TDP-43 have an important role in ALS?

Investigating TDP-43 palmitoylation as a therapeutic target to lower protein aggregation

$75,000 awarded to Lucia Meng Qi Liao, a PhD student in Dr. Dale Martin’s lab at the University of Waterloo

In over 97 per cent of all ALS cases a protein called TDP-43, which is normally found within the nucleus of a cell, becomes trapped outside in the cytoplasm where it forms clumps or aggregates. While mutations in the TDP-43 gene are responsible for this dysfunction in a small subset of cases, the cause for most people living with ALS still unknown.

With this award, Lucia aims to characterize the role that palmitoylation may play in TDP-43 dysfunction. Palmitoylation involves the addition of a small tag to a protein that can influence how it functions and where it’s located within a cell. Preliminary results show that TDP-43 is palmitoylated in cells and that this may contribute to the cytoplasmic buildup and aggregation often seen in ALS.

Using both cellular and animal models, Lucia will determine the locations where palmitoylation occurs on TDP-43, as well as what enzymes play a role in the process. She will also explore the relationship between palmitoylation and another common protein modification, called nitrosylation, to better understand how these two processes may influence one another and contribute to ALS.

Understanding how TDP-43 dysfunction could be regulated through palmitoylation is of great interest as the outcomes of this work could contribute to our understanding of almost all cases of ALS and potentially open new avenues of exploration for developing future ALS treatments.

How do ALS-linked genes contribute to the loss of normal stress granule formation?

Elucidating the role of stress granule dynamics in the pathogenesis of ALS

$75,000 awarded to Charlotte Manser, a PhD student in Dr. Derrick Gibbing’s lab at the University of Ottawa

Stress granules are protective structures that healthy cells make when they are exposed to environmental stress. Stress granules protect vulnerable RNA (molecules that translate genetic instructions and oversee protein production) from becoming damaged. Once the stress passes, the stress granules break apart and RNA resumes its work within the cell. Recent evidence suggests that disruption of proper stress granule biology may play a central role in ALS disease processes.

In this study, Charlotte will investigate how various ALS-linked genes influence stress granule dynamics within cells and how this may impact the mislocalization of TDP-43, an ALS-linked protein known to become trapped in abnormal stress granules. Once she has identified the genes that have a significant effect, Charlotte will validate her findings in motor neurons derived from stem cells. Finally, using a mouse model of ALS, she will explore the mechanisms by which these gene candidates alter stress granule dynamics and TDP-43 function.

By systematically investigating the role of various ALS-linked genes in key disease processes, this work will help to increase our understanding of the biological pathways that underly ALS. The information gained from this study should provide valuable insight into the cellular processes that take place when stress granules assemble and disassemble, which is essential to developing future treatments aimed at maintaining healthy stress granule dynamics and ultimately slowing or stopping the progression of ALS.

How does tRNA function contribute to ALS disease processes?

Aberrant tRNA function exacerbates TDP-43 misfolding and toxicity in cellular models of ALS

$75,000 awarded to Donovan McDonald, a PhD student in Dr. Martin Duennwald’s lab at Western University

DNA holds the master code of genetic instructions that oversee the production of proteins, the workhorses of the cell. Proteins consist of long chains of smaller units called amino acids. The genetic information carried in our DNA is converted into proteins at a specific structure within the cell, called the ribosome. Other molecules, called tRNA, play a key role in protein formation by delivering amino acids to the ribosome to be incorporated into proteins. New evidence suggests that abnormal functioning of tRNA may contribute to errors in protein formation that lead to protein misfolding, a common feature seen in many neurodegenerative diseases, including ALS.

With this award, Donovan will investigate the effects that abnormal tRNA function have on TDP-43, a protein known to be affected in nearly all ALS cases. Using a yeast model, Donovan will first explore how a common mutation in tRNA contributes to the misfolding of TDP-43. Then, he will determine how genes known to regulate tRNA function influence TDP-43 dysfunction. Finally, he will investigate how a specific protein associated with a familial form of ALS, called angiogenin, influences tRNA and subsequently TDP-43.

The abnormal functioning of tRNA has not been well studied in ALS to date. It is clear that tRNAs perform many functions in cells that, if interrupted, may contribute to disease. The results of this work will add another piece to the ALS puzzle, providing new knowledge in a previously unexplored area. Additionally, this work could help to identify new risk factors, biomarkers, and possibly new treatment targets for ALS.

Postdoctoral Fellowship

Could neuronal reprogramming serve as a potential treatment strategy for ALS?

Neuronal reprogramming as a novel therapeutic strategy to treat amyotrophic lateral sclerosis

$165,000 awarded to Dr. Hussein Ghazale, a postdoctoral fellow in Dr. Carol Schuurmans’s lab at Sunnybrook Research Institute

Direct neuronal reprogramming is a new technology that allows researchers to convert cells from one type to another. In the past, this type of cellular programming was only achievable when using stem cells as a starting point. Now researchers can take an already differentiated cell, such as an astrocyte, and covert it to what is called an induced Neuron (iNeuron).

Using a mouse model of ALS, Dr. Ghazale will attempt to convert astrocytes within the motor cortex to a specific type of neuron, called a GABAergic interneuron, using a viral gene delivery system. Previous studies have shown that activation of these GABAergic neurons helps to preserve motor function in mice. Additionally, astrocytes have been shown to become reactive in ALS, releasing toxic factors that may contribute to disease progression. The hope is that by reducing the potentially toxic astrocyte population, and increasing the number of helpful interneurons, this technique may be able to delay ALS progression.

Dr. Ghazale will examine how effective the neuronal reprogramming technique is in both a mouse and human cerebral organoid model of ALS. If successful, this technique could represent a promising new avenue to explore for disease modeling, drug screening and therapeutic development in ALS.