We have been a bit quiet lately and that’s because a friend is very sick. He has amyotrophic lateral sclerosis (ALS). In order to help him, the Pathogenes team needed to catch up on the particulars of this most horrible disease. There is no cure for ALS and quite frankly, no useful treatments. It has taken us a few months to read stacks of papers and gather a team of experts. And form a plan. Our plan isn’t simple and it isn’t easy. It’s complicated and can change. As we formulate and fine tune our approach to stopping the progression of ALS our experts review our work for scientific accuracy and feasibility. We don’t mind that no one has heard of what we propose. We will test our hypothesis and march forward.
You can find a lot of information on ALS on the Web and we won’t repeat it here. You can check out our ALS tab for some links we found useful. It is worth pointing out that there is familial ALS (fALS) in which genetics plays a big part. Only 10-15% of patients with ALS (PALS)…these folks are acronym heavy…get fALS. Most people get spontaneous ALS (sALS), close to 90%. There are different camps and controversies concerning the pathways involved in disease and how to approach reversing the progress of motor neuron (MN) death, but an overriding theme of those that investigate ALS is the compassion and sharing of information. Basically, ALS is associated with an enzyme mutation (superoxide dismutase, SOD) and/or other mutations that cause MN death. Motor neurons make muscles work. You need motor neurons to breathe.
What stirred us to take a break from our bench work and communicate with our EPM-centric following is learning that dogs get spontaneous ALS! Dog-ALS is associated with the enzyme superoxide dismutase, the mutation is in SOD1. The onset of dog disease is late in life. That means there are ALS cases in people, dogs, and genetically engineered mice. Horsey people realize there are unknown causes of spontaneous neuromuscular disease in horses that cause them to be wobbly. These horses can progress until they can’t get around and are euthanized. In some cases there is no diagnosis and no treatment. We reviewed two of these diseases.
Equine Motor Neuron Disease (EMD) is an acquired neurodegenerative disease in horses affecting the lower motor neurons of adult horses. The disease is characterized by the onset of abnormal nerve function and muscle wasting resulting from the deterioration of motor neurons and myopathy. Horses from 15 months to 25 years old can get EMD. EMD is considered to be a multifactorial disease, however a dietary deficiency in vitamin E is considered to be a major predisposing factor in its development. This is largely related to when horses have a decreased antioxidant capacity leading to accumulation of free radials and that results in oxidative damage to the ventral motor neuron cells. Could a decreased function of horse-SOD be a factor?
No one knows what causes Equine degenerative myeloencephalopathy (EDM) that is a diffuse, degenerative disease which primarily causes damage to the horse’s spinal cord. EDM is considered to be an advanced form of neuron-axon dystrophy. EDM may have a genetic basis. Horses can develop EDM and equine motor neuron disease (EMD) at the same time and in association with an underlying vitamin E deficiency. Horses with EDM show clinical signs of a general proprioceptive ataxia-“I don’t know where my feet are” and an abnormal base-wide stance while at rest. Horses will usually start to show signs of EDM when they are 6 to 12 months old. Horses with mild cases of EDM may present as performance-related problems. At first the condition produces subtle signs, being nothing more than "clumsy" but ataxia slowly progresses as clinical signs are usually slow and insidious. Ataxia signs will become more apparent and worsen over time. Paralysis and spastic muscular movements will become more evident, until late stages where the horse is unable to get up from laying down without assistance. The only way to get a definite diagnosis that a horse has EDM is by conducting post-mortem examination shortly after death.
We’d like to test horses for EMD and EDM for antibody against neurofilaments. It’s a serum test. Once we have some results we will share them with everyone. If we can demonstrate that horses also have a form of ALS, and why shouldn’t they?, we can start looking at treatments in this species. If you have a horse with a diagnosis of EMD or EDM send us serum and we will test it. Be sure and have a firm diagnosis. Not just a “This is on the differential” or “It’s nothing I’ve seen before!”. Testing is expensive and we’re proposing to pay for it. We need to know and have proof that several diseases have been ruled out. You can email us for the form to send in a sample for this specific testing until we put a submission form up on our site. We want late cases as well as cases that are early.
The funny thing is that the deeper we delve into ALS and our approach to treatment, some paths seem to converge. As the ALS community gets closer to understanding the pathophysiology of disease we are finding common roads. All roads seem to be leading to Rome after all.
At some later date when we have some good news for your ALS friends we will ask you to share what we find. Until then, we are going back to work.