A GLP-1 Analog for the Treatment of ALS
Abstract
Neuroinflammation is a response to nerve cell injury. This results in the release of additional factors in the brain and spinal cord, which can cause further nerve cell damage. There is a wealth of evidence in patients as well as animal models of ALS to suggest that neuroinflammation may play a role in the disease by activating cells called microglia and astrocytes. ALS is not the only disease where this occurs. Other neurodegenerative diseases like Parkinson s disease (PD) and Alzheimer s disease (AD) also show this pattern. Therefore, the development of agents that could selectively inhibit microglia and astrocyte overactivation, resulting in toxic effects, could have profound therapeutic potential. One particular advantage of NLY01 is that because of its long half-life, patients may only need to inject this compound once weekly. This would offer a significant advantage over the currently approved ALS drugs riluzole (taken twice daily and with only a marginal effect) and the more intensive daily intravenous dosing (through a vein in the arm) of the newly approved compound edaravone. We anticipate that because NLY01 is easier to administer, this might improve compliance for patients. NLY01 activates a receptor on microglial cells thus reducing microglial and astrocyte overactivation. Because NLY01 targets a neuroinflammatory pathway thought to be relevant to ALS as well as other neurodegenerative diseases, it is likely that NLY01 may help to slow disease progression after it begins. It may be used for all types of ALS where neuroinflammation puts motor neurons of the brain and spinal cord at risk. Like any drug, there are some risks with this medication. One of the potential risks observed in our animal studies was a brief reduction in food consumption and weight. However, this effect was brief and improved over the 14-day recovery phase. No adverse effects of NLY01 were observed at any dose. Because we are aware of these results, we will be able to take precautions with our patients to prevent them. Because a pre-IND (Investigational New Drug) application to use NLY01 in Parkinson s disease has already been submitted to the Food and Drug Administration (FDA), we believe that if the proposal demonstrates that NLY01 works in our ALS animal models and human motor neuron cultures, a rapid filing of an FDA IND could be achieved within a 2-year time frame. The Johns Hopkins University has a large and active ALS clinic with extensive experience in investigator-initiated clinical trials. Therefore, we anticipate that this strategy could lead to our bringing a clinical trial in ALS patients within a year after the FDA IND is approved.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810175
Entities
People
- Nicholas J Maragakis
Organizations
- Johns Hopkins University
- United States Army