Drug-like peptides inspired by snake venom can effectively treat neurodegenerative disorders

New Delhi: Researchers from the Institute of Advanced Study in Science and Technology (IASST), Guwahati, and Tezpur University have developed drug-like peptides, inspired by snake venom neurotrophin molecules that could reduce the progression of neurodegenerative diseases at a significantly lower concentration.

Neurodegenerative disease (ND) is a major global health problem. Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s. No specific medications or effective therapeutics exist to stop, slow, or prevent these diseases.

“This study is about snake venom nerve growth factors that inspired the development of novel, safe, and effective drugs to prevent the progression of neurodegenerative diseases such as Parkinson’s disease,” researchers informed.

An effective treatment for Parkinson’s disease is the administration of levodopa (a dopamine precursor). However, prolonged use of dopamine agonists (a chemical substance that binds to and activates specific receptors on cells, causes a biological response that tends to reduce their therapeutic efficacy and lead to several adverse effects.

“Snake venom is a treasure trove of drug prototypes for various biomedical applications such as cancer, cardiovascular disease, and COVID-19. It can effectively treat neurodegenerative disorders, including Parkinson’s disease. Studies from our lab have identified, purified, and characterized nerve growth factor (NGF) from Indian Cobra and Russell’s viper venom and shown that they possess neuritogenesis (the sprouting of neurites from a cell) properties,” said the research team.

However, drug development from a native snake venom toxin is tedious due to the venom crisis, stringent regulatory requirements, and costs. To overcome the challenge, the researchers have evolved two novel synthetic custom peptides (TNP and HNP) inspired by snake venom neurotrophin molecules. Their low molecular weight, structural stability, small size, and target sensitivity make them powerful tools for conquering the limitations of using endogenous NGF as therapeutic agents.

The drug-like peptides at a low dose (nanomolar concentration) can potentially reduce the progression of the paraquat-induced toxicity and symptoms associated with the Parkinson’s disease. They have been found to be showing several anti-Parkinson activities by reducing mitochondrial dysfunction, cellular death, etc.

“The drug-like peptides could reduce the progression of neurodegenerative diseases at a significantly lower concentration. This treatment would be most effective for people with fewer symptoms at the early onset of the disease. However, in-depth investigations through in vivo, pharmacokinetic, and pharmacodynamic studies for the successful development of safe drug prototypes for neurodegenerative disorders would be needed,” the researchers recommend.

The team comprised Dev Madhubala, Aparup Patra, Taufikul Islam, Kangkon Saikia, Mojibur R. Khan, Semim Akhtar Ahmed, Jagat C Borah, and Ashis K. Mukherjee. The study has been published in the Free Radical Biology and Medicine of Elsevier journal.

(India Science Wire)