Curing Parkinson's Disease is the Mission of San Diego Based Company

Neurodegenerative diseases such as Parkinson’s have been inert to medicinal treatment partly because most drugs cannot reach the central nervous system (CNS). Why? There is a physical barrier, known as the blood-brain barrier (BBB), inside the brain that protects the CNS from harmful substances in the blood such as viruses, bacteria, parasites, chemicals and biological substances. Only nutrients needed for the brain can cross the BBB into the CNS. Mother Nature made this barrier for our own protection. Unfortunately, when something goes wrong in the brain, the protective action of the BBB does not allow most pharmaceuticals/drugs to enter the CNS. As a consequence, most brain diseases have been immune to therapeutic intervention, which has been a global medical challenge for centuries both in humans and animals. A company in San Diego has come a long way to overcome hurdles of the BBB impermeability.

It has developed a technology to deliver drugs into the CNS. This technology was validated in a mouse model last year by a world renowned UCSD neurologist. Now this company has gone even further. It announced on February 22nd that its scientists have developed a blood-brain barrier (BBB) permeable therapeutic drug to control the function of one of the most prominent Parkinson’s disease targets, alphaSynuclein, which is involved in the formation of Lewy bodies.

In laboratory experiments this candidate drug has been shown to interact with the Parkinson’s pathogen with high precision at a very low dose. With this begins our journey on the “Road to Cure Parkinson’s Disease.” We currently have small quantities of this potentially powerful drug. The goal is to generate large quantities for a comprehensive study to establish therapeutic efficacy initially in animals and then in humans. The animal study will involve at least 90–120 Parkinson’s transgenic mice, and probably will take 6–8 months for completion. The data from the ongoing PK (pharmacokinetics) study on the company’s Alzheimer’s drug will be useful to determine the dose regimen for the Parkinson’s drug.Last month’s article, entitled “REVERSING PARKINSON’S
Treating Neurodegenerative Parkinson’s disease”, discussed the two types of molecules in pharmaceuticals, i.e., small molecules and macromolecules. Most small molecules such as Aspirin, Motrin, and Levodopa, etc., are BBB permeable. For decades the process of drug discovery has been centered on designing, developing and selecting small molecules for treating brain disease with scant regard for non-specific targeting and organ distribution, which lead to undesirable side effects. In addition, small molecule drugs have low therapeutic indices and develop drug resistance shortly after initial treatment.

A handful of FDA approved small molecule drugs that slow down the disease symptoms in some patients stop working after some period, leaving the patient helpless. Daily we see our friends and relatives inflicted by Parkinson’s frequently changing medications, trying to adjust dose and consulting different  physicians in search of a better drug, which so far, sadly, does not exist. Thus, in spite of remarkable BBB permeability, the small molecules based drugs have been plagued with lack of specificity, development of drug resistance, low therapeutic indices and frequent administration, in addition to being inept to cure the disease.Macromolecules are large molecule modern drugs such as proteins and antibodies which are otherwise effective in laboratory experiments outside the human body, but have been discarded during their development for clinical use due to a failure to deliver them in sufficient quantity to the CNS. Antibodies are molecules of unsurpassed specificity but conventional antibodies do not cross the BBB. Antibodies are molecules which humans make against a foreign substance such as a cold virus to neutralize its effect but these antibodies are too big to cross the BBB. Although neurodegenerative diseases have been known for many decades and despite enormous research efforts both by private sectors and government institutes, due to the hurdles of BBB, there are no diagnostics and curative treatments for Alzheimer’s and Parkinson’s diseases. Similar to antibodies, most pharmaceutical drugs are also unable to cross the BBB into the CNS, making brain disease inert to drugs.

With more than 50 million people afflicted worldwide by neurodegenerative diseases, this epidemic summons an immediate response from local, national and international communities to develop early diagnosis and treatment. With the aging population living longer, the number of people suffering from neurodegenerative diseases will continue to escalate unless highly specific curative drugs (minimally toxic) are developed today. Disease curative drug is the one that, in addition to treating the symptoms, halts the disease progression. In the January issue of Newsworthy Notesappeared the article PARKINSON’S DISEASE A COLLABORATIVE, which focused on identifying the key issues, which have been in the way of developing curative treatment for neurodegenerative diseases. The main issues were: 1) Limited understanding of the disease etiology; 2) The inability of most drugs to go across the blood-brain barrier (BBB) into the central nervous system (CNS). Continued efforts to understand etiology have lead to the identification and characterization of the key pathogenic proteins involved in causingParkinson’s.

Most neuroscientists believe that therapeutic intervention to regulate the function of some of the already identified pathogenic proteins will alleviate, halt, and/or reverse the disease process. Realizing the urgent medical need, a small Biotech Company based in San Diego, California, has undertaken the challenge of developing diagnostics and therapeutics for the world’s most debilitating neurodegenerative Alzheimer’s and Parkinson’s diseases. Funded by a grant from the US Government and angel funds, the company first focused upon tackling one of the biggest challenges of medicine, which was to overcome the hurdles of Blood Brain Barrier (BBB) impermeability. After two years extensive research efforts, the company’s scientists developed a proprietary technology which breached the hitherto impermeable BBB in a mouse model. The validation of its technology was done by a well known UCSD neuroscientist.

To demonstrate BBB permeability, the scientists developed an Alzheimer’s disease specific pharmaceutical macromolecule, which when injected in the tail vein of a mouse traveled across the BBB into the CNS where it specifically bound with the amyloid-plaque found in the brain of Alzheimer’s transgenic mouse. Having demonstrated BBB permeability, the company is now trying to scale up the production of its drug to establish therapeutic efficacy against Alzheimer’s disease.Having been encouraged by the BBB study of its Alzheimer’s drug, the company launched a program last October to develop BBB permeable therapeutic molecules for Parkinson’s disease. It has now developed a drug to neutralize one of the pathogenic proteins, alphasynuclein, with a known link to Parkinson’s. The company is now in the process of gathering resources to advance this potential pharmaceutical to preclinical and clinical trials.