ALS Treatment Shown Safe, Affects Key Proteins

(NIH.gov)

19 Sept. 2022. Results of a clinical trial show a combination of two approved drugs changes levels of proteins associated with ALS, with patients experiencing few adverse effects. Researchers from the biopharmaceutical company Neurosense Therapeutics Ltd. in Herzliya, Israel and Cambridge, Mass. reported the findings last week in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.

Neurosense Therapeutics develops therapies for neurodegenerative disorders, with its lead product called PrimeC designed as a treatment to limit the progression of ALS. Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a progressive disease where neurons controlling muscles in the body start wasting away, and can no longer send or receive signals from the brain or spinal cord. As neurons cease functioning, muscles in the limbs, and later speech and breathing muscles, weaken and eventually stop functioning. Most people with ALS die of respiratory failure. There are currently no cures for ALS, and few effective treatments for slowing its progression.

PrimeC is Neurosense’s own combination of two drugs, ciprofloxacin and celecoxib, currently approved for other diseases. Ciprofloxacin is an antibiotic prescribed to treat bacterial infections such as pneumonia, gonorrhea, and typhoid fever, as well as biological weapons such as anthrax. Celecoxib is a nonsteroidal anti-inflammatory drug given to relieve pain, stiffness, and swelling from osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, a form of arthritis affecting the spine. The drug works by blocking cyclooxygenase or COX enzymes that cause pain and inflammation.

Two protein indicators in blood samples

The mid-stage clinical trial enrolled 16 people living with ALS at Sourasky Medical Center in Tel Aviv, Israel, with 15 of those individuals taking part and 12 completing the study. Participants took PrimeC capsules three times a day for 12 months. The trial’s primary goal was to assess the safety of PrimeC in ALS patients, but also reveal chemical changes in participants that suggest the treatments are working as intended.

To assess chemical changes in the body, researchers tested patients’ blood samples for exosomes, natural oil extracellular vesicles or bubbles emitted by neurons, in blood serum. The Neurosense team looked mainly for two protein indicators in the blood serum samples: TAR DNA-binding protein 43, or TDP-43 and light chain 3, or LC3. Accumulations of TDP-43 are common in people with neurodegenerative diseases, including ALS, while LC3 is associated with autophagy, a process for clearing the body of misfolded or aggregated proteins.

Findings show four of the 15 participants experienced adverse effects from PrimeC, with most rated mild or moderate, and none considered serious. At the start of the study, the researchers tested trial participants for their levels of TDP-43 and LC3 proteins compared to matched healthy individuals, which shows ALS patients with more TDP-43 than healthy individuals, but lower levels of LC3. After 12 months, the team found TDP-43 levels decrease in ALS patients, but LC3 levels increase, compared to the start of the study.

“This clinical study is a very important achievement and milestone for the ALS community,” says Vivan Drory, director of neuromuscular diseases at Sourasky Medical Center and principal investigator in a Neurosense Therapeutics statement. “It is very encouraging to see that there was both biological activity and clinical signals of a treatment effect.”

Based on the findings, Neurosense Therapeutics says it began another mid-stage clinical trial, testing PrimeC against a placebo among ALS patients.

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