Working Faster Than the Speed of ALS to Transform Neurodegenerative Disease Research
By: Soumya Shashikumar, MBiotech
Interviewee: Karen Ho, PhD, MSc, Vice President of Translational Medicine, Clene Nanomedicine
Working Faster Than the Speed of ALS to Transform Neurodegenerative Disease Research
By: Soumya Shashikumar, MBiotech
Interviewee: Karen Ho, PhD, MSc, Vice President of Translational Medicine, Clene Nanomedicine
Neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Parkinson’s disease (PD) represent some of the most challenging medical conditions, with ALS, often known as Lou Gehrig’s disease, leading the way as a fatal motor neuron disorder.
ALS causes the progressive degeneration of nerve cells in the brain and spinal cord, beginning with limb weakness and rapidly progressing to severe muscle atrophy, paralysis and ultimately death, often due to respiratory failure. Affecting approximately one in 50,000 people worldwide, ALS predominantly strikes men between the ages of 40 and 70, though it can occur earlier. With no cure available, current treatments focus on symptom management and improving the quality of life for those affected.
At the forefront of efforts to change the course of these devastating diseases is Clene Nanomedicine, a company pioneering the use of nanotechnology to develop breakthrough therapies. Their innovative approach leverages the unique properties of nanocrystals to create disease-modifying therapies, with one of the most promising developments being CNM-Au8, an investigational drug for ALS that uses gold nanocrystals.
Leading these efforts is Karen Ho, PhD, MSc, Vice President of Translational Medicine at Clene Nanomedicine. Dr. Ho’s commitment to improving the lives of those burdened with ALS is more than a professional pursuit; it is an inspiring mission. Here, Dr. Ho shares her insights into the challenges and advancements in the field of neurodegenerative diseases.
The Story Behind the Speed of ALS
Dr. Ho’s dedication to ALS research is as much about compassion as it is about science. During the interview, she spoke about Brooke Eby, an ALS advocate who has become an inspiration for many, including Dr. Ho.
“She [Brooke Eby] said that she has to live at the speed of ALS because her disease might kill her in two to five years. So, here's a young woman in her early thirties who now wants to cram as much of the richness and fullness of life experience into two to five years. At Clene I take this challenge seriously: let's develop a drug for ALS patients faster than the speed of ALS,” expressed Dr. Ho.
ALS is a brutal disease, often leaving patients with only a few years to live after diagnosis. Dr. Ho’s reflections on this reality underscore the importance of accelerating the development of new treatments. With heartfelt determination, she shared, “Let’s not let another person be told that there’s nothing we can do for you. Let’s instead be able to look them in the eye and say, we’re doing everything we can for you.”
Gold Nanocrystals — Insights into Nanomedicine
Central to Clene’s efforts is CNM-Au8, an oral suspension containing gold nanocrystals. This investigational drug, with completed Phase II trials, is being studied as a potential treatment for ALS, MS and PD. CNM-Au8 works by improving the health of mitochondria — the energy producers in our cells — while also reducing harmful oxidative stress and lowering levels of misfolded proteins. These actions help protect neurons, the cells that are most affected by these diseases.
Dr. Ho elaborated on the mechanism of action of CNM-Au8, explaining how gold nanocrystals, when engineered with clean surfaces, exhibit extraordinary catalytic and therapeutic activities.
“With CNM-Au8, we would expect to see activation of some mitochondrial markers,” Dr. Ho explained. “We would see higher levels of NAD+, and higher levels of the NAD+ to NADH ratio, just to give some examples. And we’d also like to see a decrease in toxic oxidative markers and an activation of an antioxidative response.”
Research suggests that NAD+, a molecule involved in energy production, plays a role in the progression of ALS. By boosting NAD+ levels and improving mitochondrial health, CNM-Au8 could offer a new approach to slowing the progression of neurodegenerative diseases.
“For neurodegenerative diseases, we as drug developers can give more options to medical doctors so that they don't have to look a patient in their eye and say, 'I'm sorry, there's nothing more that I can do.' I think that that's my great hope and I think it's going to take the entire field of drug developers to get there. It's not going to be just one drug. It's going to be an entire effort.”
— Karen Ho, PhD, MSc, Vice President of Translational Medicine, Clene Nanomedicine
“For neurodegenerative diseases, we as drug developers can give more options to medical doctors so that they don't have to look a patient in their eye and say, 'I'm sorry, there's nothing more that I can do.' I think that that's my great hope and I think it's going to take the entire field of drug developers to get there. It's not going to be just one drug. It's going to be an entire effort.”
— Karen Ho, PhD, MSc, Vice President of Translational Medicine, Clene Nanomedicine
The Role of Biomarkers in Neurodegenerative Treatment
Dr. Ho’s work is closely connected to the use of biomarkers — measurable indicators that can show how well a treatment works. She discussed two types of biomarkers that are particularly relevant for neurodegenerative disease research: target engagement biomarkers and disease progression biomarkers.
“The power of these biomarkers is that they’re a window into the brain which we can't open up and dissect and look at in humans. In the cases of serious life-threatening diseases such as ALS, where lifespan is severely cut short, biomarker data can be pivotal in accelerating the drug's approval,” said Dr. Ho.
One particularly important biomarker Dr. Ho mentioned is neurofilament-light chain (Nf-L), a protein that stabilizes neurons but is released into the bloodstream and cerebrospinal fluid (CSF) when neurons are damaged. High levels of Nf-L are a sign of active neurodegeneration. By monitoring this biomarker, researchers can assess whether therapies and drugs are able to protect neurons.
“We would be looking to see whether or not treatment with a drug such as CNM-Au8 could lower those levels of Nf-L and that would be a signal that now we are preserving neuronal health and function,” she explained.
The Future of ALS Research: Nanomedicine and Beyond
The promise of nanomedicine doesn’t stop with gold nanocrystals. Dr. Ho also discussed the potential of using other metals and alloys in similar treatments. These nanocrystals have unique properties that make them effective in a wide range of applications.
Dr. Ho is excited about the future of this field and emphasized the importance of staying curious and innovative, saying “My hope for nanomedicine is that with Clene's pioneering the first nanotherapeutic that is catalytically active, I think that there's an opening and opportunity to start to explore other ways and other materials that we could use to treat these hard-to-treat, forgotten diseases with high unmet need and actually really impact millions of lives of people who suffer from these diseases.”
Dr. Ho also highlighted the significant role of patient advocacy in driving progress in ALS research. She highlighted how organizations like I AM ALS and ALSA [The ALS Association] have been instrumental in bringing patient voices to the forefront of research and clinical trials. This increased patient involvement has been transformative for the field, leading to more informed research and stronger partnerships between scientists and the ALS community.
Looking ahead, Dr. Ho sees a future where drug development is a collaborative effort. She believes that advances in technology and medicine will work together to give doctors more options for treating neurodegenerative diseases.
Dr. Ho recognized that the fight against these diseases will require a comprehensive approach. “It’s not going to be just one drug. It’s going to be an entire effort, and that’s totally fine,” she said. “And it’s exciting to be part of that effort.”
ABOUT Karen S. Ho
Dr. Ho is Head of Translational Medicine at Clene, where she leads the development of our drug candidates from basic science to early clinical studies. She is responsible for generating scientific insights into mechanism and efficacy, as well as much of the scientific communications about Clene’s catalytic nanomedicines. She leads biomarker development, scientific collaborations, presentations, publications, grant writing and some of the company’s PR efforts. Prior to Clene, she was the lead scientist at a startup diagnostic testing company, where she streamlined and innovated new methodologies for the scientific interpretation of genetic testing results for children with autism, developmental delays and/or cognitive impairment.
After receiving her Bachelor of Science degree in Biochemistry summa cum laude from Washington University as a Compton Scholar, Dr. Ho lived in England for two years where she earned a Masters degree in Genetics from the University of Cambridge as a Marshall Scholar. She has a PhD in Developmental Biology from Stanford and completed her postdoctoral training as a National Sleep Foundation Pickwick Scholar and Howard Hughes Medical Institute Postdoctoral Fellow at University of Pennsylvania in the Department of Neuroscience. Dr. Ho serves on several rare disease group Scientific Advisory Boards and holds a concurrent position as adjunct faculty at the University of Utah School of Medicine in the Department of Pediatrics, Division of Medical Genetics.