Background: Amyotrophic lateral sclerosis (ALS), or 'Lou Gehrig's Disease,' is a tragic health problem that affects approximately 30,000 Americans and is twice as common among military Veterans than among civilians. We do not understand why Veterans have a higher risk of ALS. The disease causes muscle paralysis and typically leads to death within 2-5 years of diagnosis. Because no current drugs cure or significantly extend the lives of ALS patients, new medicines are urgently needed. Our team at Mayo Clinic will use an entirely new method to find drugs that will protect nerve cells in ALS patients and stimulate their growth and health. Our method sifts through 100 trillion, minutely small DNA strands to find just the right shapes that stick to nerve cells and trigger them to survive and repair. Our team has previously made progress treating mice with ALS symptoms and our technology has shown promise in treating mice with multiple sclerosis (MS) symptoms.
Ultimate Applicability of the Research: We are using a new technology to find molecules that have the potential to bind to damaged neuron cells in ALS patients and improve the health of the cells or trigger them to regenerate. Our work will begin with cells in dishes. If progress is made, the drug molecules can be tested in the future in mice with ALS. We have experience with these animal models. If there is progress with mice, the drugs can be tested for safety in other animals, and then considered as a new drug therapy for human trials.
Types of ALS Patients To Be Helped: In principle, outcomes from this research have the potential to help all future ALS patients.
Potential Clinical Applications, Benefits, and Risks: The proposal is to discover new drugs using nerve cells grown in the lab. Future animal and human studies would determine whether patient health could be improved and lifespan extended. A prior study from our group with a larger and more complicated and expensive antibody molecule suggested that the health of mice with ALS could be improved. We seek similar results with the simpler, less expensive and more sturdy drugs studied here.
Projected Time it May Take to Achieve a Patient-Related Outcome: The drug studies in cells will take at least 2 years. Future studies using mice with ALS may require 2 to 4 years. Safety studies with other animals may require several additional years before licensing by a drug company partner for a clinical trial with human patients.
Interim Outcomes: The immediate goals are to identify one or more DNA molecules that have the desired ability to bind nerve cells and trigger favorable nerve health and regeneration when used with cells growing in the laboratory.
Likely Contributions of This Study in Advancing the Development of Therapeutics for ALS: The concept of regenerative therapy is an important new idea. Drugs of this kind stimulate the body to help itself. Our approach to regenerative drugs uses a new technology: Sifting through trillions of possible drug shapes to find the shapes that stick to nerve cells and tickle them in just the right way to induce them to change their behavior even when damaged by ALS. Our study will be the first to employ this approach for ALS and will reveal the strengths and weaknesses of this important new method for discovering drugs.
|Effective start/end date||1/1/21 → …|
- Congressionally Directed Medical Research Programs: $795,000.00