" class="no-js "lang="en-US"> ALS Gene Therapy Demonstrates Bioactivities in a Disease Model
Sunday, March 03, 2024

Gene Therapy Candidate for Amyotrophic Lateral Sclerosis (ALS) Demonstrates Bioactivities in a Murine Model of the Disease

Anew Medical, a medical product development company, announced results presented at the European Society of Cell and Gene Therapy (ESCGT) from preclinical in vivo studies of its lead secreted-Klotho (s-KL) gene therapy candidate in a stringent animal model of human ALS. The SOD1G93A mouse model recapitulates most of ALS neuromuscular abnormalities, and it’s been shown that there are decreased mRNA levels of s-KL protein expressed in skeletal muscles, the motor cortex, and the lumbar spinal cord in these animals. Thus, long-term supplementation of the s-KL protein via gene therapy technology is an attract new measure for treatment of this deadly disease.

The technology was licensed on an exclusive worldwide basis from the Universitat Autonomo de Barcelona in Barcelona, Spain. ANEW’s lead gene therapy candidate utilizes a muscle-targeting AAV9 viral vector and a muscle tissue-specific promoter upstream of the s-KL gene to selectively express the s-KL protein in the muscles and nervous system of transgenic mice that overexpress the SOD1G93A gene, leading to the clinical signs and symptoms of ALS, also known as “Motor Neuron Disease” and “Lou Gehrig’s disease”. The overexpression of the SOD1 gene in humans is called “familial ALS” and occurs in 5%-10% of all ALS cases.

ALS is a progressive neurologic disorder characterized by the loss of cortical and spinal motor neurons, denervation of nerve endplates, axonal retraction and death to motor neurons resulting in muscle atrophy. Patients average 2-3 years of survival after initial diagnosis, so there is an urgent medical need for effective treatments of this deadly disease. The ALS neuropathology is mainly due to oxidative stress, neuroinflammation, excitotoxicity and mitochondrial dysfunction leading to loss of muscle mass, muscle endplate denervation, and ultimately death from respiratory failure.

Results show that the overexpression of the s-KL protein in muscles and CNS, mediated by the s-KL gene, a muscle-targeted AAV vector, and the muscle-specific promoter enhances motor function, yields higher number of innervated neuromuscular junctions, reduced oxidative stress and neuroinflammation, produces higher muscle action potential of major muscle groups, induces improved muscle strength and muscle mass, reduces glutamate-induced excitotoxicity in the spinal cord, delays the disease onset, and improves overall survival versus the non-treated control groups.

Dr. Joseph Sinkule, the Company’s CEO stated, “Our s-KL gene therapy construct exhibits robust and prolonged bioactivity in this model of ALS and these results support ALS as the first indication in clinical trials of this new approach to treat ALS. We look forward to expanding the testing of our lead candidate, ANEW-202, in the Profilin1 animal model of ALS that represents 90-95% of all human ALS cases called Sporadic ALS. The delivery and expression of the s-KL protein by the s-KL gene may be an effective therapy in this degenerative neuromuscular disease.”

“The data open up additional avenues for the use of ANEW-202 in an expanding array of other neuromuscular and motor neuron diseases such as multiple sclerosis, muscular dystrophy, myasthenia gravis, and rare diseases like Lambert-Eaton disease, Friedreich’s ataxia, and spinal muscular atrophy. There may even be potential use in spinal cord injuries and peripheral nerve injuries but clearly, ALS is our lead indication,” says Dr. Sinkule.

  1. Eloxx Pharmaceuticals Announces Final Data Assessment from Phase 2 Combination Clinical Trial of ELX-02 in Class 1 Cystic Fibrosis Patients Read more
  2. Verge Genomics Announces Positive Safety and Tolerability Data from the Phase 1 Clinical Trial of VRG50635, a Potential Best-in-Class Therapeutic for All Forms of ALS Read more
  3. DEM BioPharma Appoints Wendy Young, Ph.D., to Scientific Advisory Board Read more
  4. Confo Therapeutics Enters into Research Collaboration for GPCR-Targeting Antibody Discovery with AbCellera Read more
  5. Vyriad Announces Expansion of T-Cell Lymphoma Trial at Mayo Clinic Read more