Despite the work of researchers around the world, ALS is still a poorly understood disease. Because there are so many unknowns surrounding the disease, the most important research is conducted in labs, instead of human trials. We believe that once we understand the basic, biological cause of ALS, we will be able to begin developing effective therapies.
The Frances and Joseph Weinberg Research Unit, part of the Jefferson Weinberg ALS Clinic, is the first and only center in Philadelphia dedicated solely to ALS research. The Weinberg Center was established in 2006, thanks to the generosity of Vickie and Jack Farber.
Identifying the role of the blood-brain barrier in treating ALS
There are two FDA-approved medications for ALS. They are riluzole, which has been available for many years, and edaravone, which was approved in 2017. Riluzole appears to be very effective at slowing disease progress for about six months. Then it slowly becomes less effective. Eventually, riluzole stops slowing down disease progression at all.
This problem may be caused by the patient’s own body. Our brain is protected by a system called the blood-brain barrier. This system helps protect our brain from toxins. The barrier has two parts: a membrane, or physical barrier, and ABC pumps. If toxins make it past the membrane, the ABC pumps are supposed to identify them, capture them and pump them away from the brain.
Eventually, the nervous system of a person who has ALS realizes there is a problem. In an effort to protect the body, the ABC pumps become more sensitive. Unfortunately, it appears this means the ABC pumps begin to identify riluzole as a toxin. They capture the medication and pump it away from the brain.
Jefferson researchers are working on finding a medication that can slow the ABC blockers. If a medication is found, it may be able to be paired with riluzole. If riluzole can enter the brain for a longer period of time, we may be able to slow the progression of disease.
Communication between the spinal cord motor neurons and the muscle cells
Our spinal cord is made up of motor neurons. These are special kinds of cells that help control muscles. They are help facilitate communication between the motor neurons and the muscle cells. People living with ALS connected to the cells in our muscles by an area called the neuro-muscular junction. There are proteins that produce fewer and fewer of these key proteins as the disease progresses. It is believed this is a major cause of the weakness people with ALS experience.
Our scientists are investigating what causes this shortage of proteins. This could pave the way for research into a medication that can help preserve these proteins. Preserving these proteins may help preserve quality of life in ALS.
Malfunction of astrocytes
Astrocytes are the nervous system’s supportive cells. They produce and secrete proteins that help the rest of the nervous system function. In people with ALS, the astrocytes begin to secrete toxic proteins. These toxic proteins seem to quicken the progression of ALS.
Jefferson researchers are trying to find out what causes the astrocytes to secrete these toxic proteins. Once this question is answered, researchers hope to develop a medication to stop the secretion of these toxic proteins. This could either slow or stop the progression of ALS.
Role of C9Orf72
Everyone has the gene C9Orf72. However, some people have a mutation of that gene that is known to cause ALS. Unfortunately, no one currently knows why that mutation occurs.
Jefferson researchers are investigating a number of angles surrounding this mutation. One theory is that people with this disorder secrete too much C9Orf72 protein. If this is the cause, a treatment plan could include a drug that suppresses the secretion of this protein. Another theory is that people with the mutation secrete a toxic version of the C9Orf72 protein. If this theory is found to be true, a treatment option may involve a medication that reduces production of the protein.
Malfunction of nucleic acids
Nucleic acids are a normal component of our DNA. People with ALS may have abnormal molecular structures that absorb proteins, like a sponge. This prevents the proteins from continuing their normal function within the body.
If this is found to be the case, we could begin developing a therapy that involves introducing an artificial substance to “fill up” the “sponge.” This could allow the proteins to continue their normal function within the body.
Make an Appointment
Appointments are available every Friday for patients with a confirmed diagnosis of ALS. Diagnostic services are also available. If you have been told you have ALS, or have been asked to see an ALS specialist for a possible diagnosis, we can help. Please call the Jefferson Weinberg ALS Program Manager, Kate Monahan at 215-503-4294 or 215-955-8800.
Find out how you can support Thomas Jefferson University and Hospitals to make a difference in the research and treatment of ALS.