Update on the Road to the Cure - January 2022

A Real-Time Science Report

Ram S. Bhatt, PhD., Chief Science Officer

ICBII is named among big pharma developing technology to cross the BBB

Parkinson’s Cure May Be Closer than Ever!

In the November 2021 Newsletter we briefly discussed two of the many reasons for past failures in developing curative therapies for Parkinson’s disease. They were: 

1) The blood-brain barrier (BBB) that blocks the entrance of most pharmaceuticals from reaching the brain; and, 

2) Too much focus on clearing protein aggregation from the brain of patients despite failure of multiple clinical trials over the last two to three decades. The global scientific community erroneously assumed that by using the same approach (use of mouse monoclonal antibodies with very poor brain uptake) again and again will result in a better outcome, which never happened. We also stated in the November 2021 Newsletter that by the time aggregated protein starts appearing at detectable levels in the brain, most of the neurons have already been compromised. Without the clear understanding of what the initial trigger is that kills neurons in the vital part of the brain, there won’t be a cure for years to come. With its BBB permeability technology, ICB International has the tools to understand and reverse mechanisms that initially trigger neuronal death in Parkinson’s and other central nervous system diseases.   

PARKINSON’S DISEASE ETIOLOGY:  At present, the exact etiology and pathogenesis of Parkinson’s disease remain elusive despite massive effort by the global scientists. However, many studies have shown that multiple mechanisms are involved in the pathogenesis of Parkinson’s, such as alpha-synuclein (α-Syn) oligomerization, lysosomal dysfunction, mitochondrial damage, neuroinflammation, genetic factors and gut microbiome. Thus, Parkinson’s is a multifactorial neurodegenerative disorder. Without correcting and/or rejuvenating the processes that lead to neuronal death it wouldn’t be possible to cure neurodegenerative diseases. The drug must pass the BBB and reach the central nervous system in concentrations high enough to exert its therapeutic effect.

1. Lysosomal Dysfunction: Lysosomes are enzymes whose function is to break down unwanted proteins and cellular debris. It seems that in healthy individuals’ lysosomes function properly to clear the excess cellular debris but not in Parkinson’s patients. Lysosomal dysfunction might be a prominent and early event in Parkinson’s. Therefore, it makes sense to find ways to rejuvenate lysosomal machinery in Parkinson’s patients, which cannot be done without the drug crossing the BBB and entering the neurons to correct the lysosomal function.

2. Dysfunctional Mitochondria: The primary function of mitochondria is to convert foods we eat into energy in the form adenosine triphosphate. They also store calcium for cell signaling activities, generate heat, and mediate cell growth and death. The damage to the mitochondrial function can result from several causes, including impairment of constant generation of mitochondrial (biogenesis), increased reactive oxygen species (ROS) production (environmental effects), clearance of defective mitochondrial (lysosomal defect), calcium (Ca2+) imbalance, and accumulation of proteins such as PINK1 and α-synuclein in mitochondria (lysosomal defect). If these insults cannot be overcome by protective mechanisms, a relentless cycle of dysfunction will eventually evoke all these dysfunctions, leading to cellular impairment and ultimately cell death. It is believed that the accumulation of proteins inside the mitochondria is accompanied by the opening of permeability pores in the membrane resulting in mitochondria dysfunction, and ultimately neuronal death.

3. Neuroinflammation: Inflammation is the body’s natural way of mounting defense against any injury. What triggers neuroinflammation in Parkinson’s is still somewhat elusive but there are some logical explanations. Microglia are the resident macrophages of the central nervous system (CNS) acting as the first line of defense in the brain by phagocytosing harmful pathogens, aggregated proteins, and cellular debris. Aggregation of misfolded α-Syn in the brain is known to activate microglia that leads to neuroinflammation. Activated microglia damage neurons by several mechanism: i) ingesting damaged neurons and degrading them directly, leading to neuronal death; ii) secreting many proinflammatory factors, such as IFN-γ, IL-2R, and TNF-α; iii) phagocytizing aggregated α-Syn and promoting its spread to healthy neurons; iv) transforming astrocytes into toxic cells that damage neurons.

Due to space limitations in the newsletter, we will discuss the role of genetic factors and gut microbiome in the next newsletter.

Hope for the Cure: Though the recent scientific progress has shed light on the complex etiology of Parkinson’s, the good news is that ICB International, Inc., has the technology to address all the parameters that lead to the neuronal dysfunction long before the symptoms manifest in Parkinson’s patients. The company has the technology that delivers drugs to the brain in much higher concentrations than any other technology developed by the global scientists. In addition, more than one target in the CNS can be targeted by a single drug by the company’s proprietary technology. The company is expecting to close the current round of financing in the near future which will enable its scientists to generate the needed momentum to take its drugs to the market.

Editor’s Note: “Nature” is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology based on its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance, and surprising conclusions. A review article entitled “Strategies for delivering therapeutics across the blood–brain barrier (BBB)” published in May 2021 in Nature by scientists of international companies such as AbbVie and Pfizer, has named ICBII among big pharma who are developing technology to cross the BBB. The Abstract of this review article reads: Achieving sufficient delivery across the blood–brain barrier is a key challenge in the development of drugs to treat central nervous system (CNS) disorders.

WOULD YOU LIKE TO HELP get ICBII’s drugs to market faster? The joy of being a part of this historical event can be had by helping ICBI find the funds to bring these trials to fruition through your investing, and by finding others with the financial ability and humanitarian mindset to accomplish the, until now, impossible. Please contact ICBI directly through their website ICBII.com or by phone 858-455-9880, or contact Jo Rosen at PRO for a personal introduction to the scientists.

IMAGINE the world without Parkinson’s, MSA, or Alzheimer’s disease.

JUST IMAGINE.