ALS - Amyotrophic Lateral Sclerosis

ALS occurs when motoneurons which control voluntary muscle movement, degenerate in the brain and spinal cord.

Patients experience rapid muscle atrophy, difficulty in breathing/swallowing and disease progression eventually leads to complete paralysis. In the absence of treatment able to slow down the course of the disease, ALS is fatal and the life expectancy once diagnosis is made is typically 2 to 5 years. During the disease progression, patients maintain normal sensory and cognitive abilities, which makes suffering particularly difficult, as they are aware of the changes happening in their body.

At any given time, it is estimated that there are approximately 400,000 people suffering from ALS.  Although the number seems quite low, it is due to the rapid fatality of the disease, and thus the very small living patient population.  It is projected that every 90 minutes, someone is diagnosed with ALS. This disease is not selective and can affect people of all ethnicities and genders. The majority of ALS (80-90%) is not hereditary and has no known cause or risk factor.

There is currently no drug that can stop disease progression. Only three drugs are currently approved and they induce only marginal benefits. Rilutek, which was the first drug approved by the FDA to treat ALS, provides only an additional three-month life extension in some forms of the disease.  Given the severity of the disease and the lack of therapeutic options, there is a clear need to develop and make available to patients a new medication to treat ALS. In this endeavor, ReMedys is working on two innovative approaches to bring relief to ALS patients.

Gene Therapy Treatment for ALS

There are two types of ALS, familial and sporadic.  Familial forms of ALS account for approximately 10% of ALS cases and a number of causative mutant genes have been identified. 20% of those familial ALS cases, the disease is caused by missense mutations in a gene called superoxide dismutase 1 (SOD1). Mutated SOD1 protein has a higher propensity to misfold and these abnormal forms of the protein acquire new toxic properties leading to neurodegeneration ("gain-of-function").

The gene therapy approach we are developing aims at specifically suppressing the mutant SOD1 mRNA, to avoid the expression of the toxic gene product. To achieve the elimination of the mutant RNA, we use a strategy called RNA interference, a mechanism used by nature to regulate the levels of messenger RNAs. Our gene therapy is based on a micro RNA designed to silence the human SOD1 gene. The sequence encoding the micro RNA is packaged into a viral vector (adeno-associated virus (AAV)) and the resulting vector suspension is injected in to the cerebrospinal fluid. The virus will dock to the cells and deliver the genetic material to the nucleus. This leads to long-term expression of the miRNA to reduce the level of mutant SOD1 following a single vector injection. Animal models of ALS have shown very promising results using this approach.

Gene therapy is again very much in the focus of innovative and targeted treatment options for many diseases following the approval of Glybera (for lipoprotein lipase deficiency) in Europe in 2012. (1) 
The approval of Zolgensma for the treatment of spinal muscular atrophy (SMA) has also raised the interest for gene therapy as a solution against neuromuscular diseases. These approved therapies are also based on AAV as the vector for delivering the corrective genetic coding material.


This highly innovative project will require extensive preclinical and toxicological evaluation as well as very controlled and sophisticated manufacturing of the therapeutic agent before it will be tested in humans. 

Gene therapy using an adenovirus vector. A new gene is inserted into a cell using an adenovirus. If the treatment is successful, the delivered gene will provide the genetic code to produce the corrective therapeutic agent locally in the cell, such as micro RNA or protein (Modified from Wikipedia:

(1) Laura M. Bryant, Devin M. Christopher, April R. Giles, Christian Hinderer, Jesse L. Rodriguez, Jenessa B. Smith, Elizabeth A. Traxler, Josh Tycko, Adam P. Wojno, and James M. Wilson. Human Gene Therapy Clinical Development. June 2013, 24(2): 55-64. doi:10.1089/humc.2013.087. Online at

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