THE MISSING LINK IN DEVELOPING CURATIVE THERAPIES FOR CNS DISEASESCategory:
UPDATE ON THE ROAD TO THE CURE
A REAL-TIME SCIENCE REPORT
THE MISSING LINK IN DEVELOPING CURATIVE THERAPIES FOR CNS DISEASES.
By Ram Bhatt, Ph.D., CSO, CEO
There is increasing evidence for the role of inflammation in neurodegenerative diseases of the central nervous system (CNS), including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). There are several basic mechanisms that drive neurodegeneration that may be triggered by inflammatory cells and their mediators at various stages of the neurodegenerative processes. Some of the mechanisms involved believed to be are: Apoptosis (caspase-mediated programmed cell death), Necroptosis (loss of cell membrane integrity), Neuronal Autophagy (cell death by accumulated toxic components such as proteins and/or damaged organelles, Retrograde Degeneration (cell death due to axonal injury), and Demyelination (damage to myelin sheath on axons). Drug development so far has been mainly focused on correcting neuronal autophagy by targeting accumulated intra- or intercellular amyloid-beta or Tau or α-Syn. Drugs used have been humanized mouse monoclonal antibodies for the targeted pathogens, which have failed in multiple clinical trials over the last three decades. As we reported last month, evidence does not exist that mouse monoclonal antibodies actually reached the target site in the brain. We would like to repeat the quote of Dr. William Pardridge once again in this November issue:
“Today, there is not a single biologic that is FDA approved for a disease of the Central nervous system where the drug traverses the blood-brain barrier following intravenous or subcutaneous administration. It is difficult to conclude, on the basis of a failed clinical trial, that a given biologic is not effective for a given central nervous system disease when the biologic was never delivered to the target site in the brain.” Bio Drugs, 31, 503 (2017)
Therefore, the failure of all of the pharma drugs may be due to the inability of drugs used in the clinical trials. On the contrary, we cannot dispute the stated claims that a group of patients treated with massive doses of amyloid-beta mouse monoclonal antibody for a long period cleared amyloid-beta from the brain of treated AD patients but without improving cognition. This failure points to a missing link in the attempted therapies so far. That missing link is the therapy to promote remyelination of axons. While it is essential to clear the brain of deleterious products either by harnessing the body’s immune system or suppressing the CNS immune mechanisms, ICBII feels that without regenerative therapies that promote remyelination, it would be difficult, if not impossible to improve cognition and or motor function. Scientists at ICB International, Inc., (“ICBII”), believe that the ideal treatment for CNS disorders will be the one that comprises:
i. Excellent blood-brain barrier (BBB) uptake of a disease-modifying drug.
ii. Regenerate and restore axonal myelination.
iii. Restore mitochondrial function.
ICBII, a San Diego based biotech company, is working on a tri-specific therapy for AD, PD, ALS, MS, and many other CNS disorders.
And a quick note on Glial cell-derived neurotrophic factor (GDNF). GDNF is a protein that promotes the survival of neurons in humans. Unfortunately, GDNF does not cross the blood-brain barrier (BBB) into the central nervous system. As a result, the therapeutic effects of GDNF have not been possible to study. ICBII has the technology to transport GDNF into the brain. Delivering GDNF to the brain is one of ICBII’s approaches to improve motor function of Parkinson’s patients after clearing the α-synuclein oligomers, the very toxin responsible for killing the neurons.
WOULDN’T YOU LIKE TO HELP get ICBII’s drugs to market faster? The joy of being a part of this historic event can be had by helping ICBI fund bringing these trials to fruition through investing, or by finding others with the financial ability and humanitarian mindset to accomplish the - until now - impossible. Please contact Jo Rosen at 760-773-5628 or jorosen@Parkinsonsresource.org or by contacting ICBI directly through their website http://icbii.com/ or by phone 858-455-9880.
IMAGINE the world without Parkinson’s, MSA, or Alzheimer’s disease. JUST IMAGINE.