TREATING NEURODEGENERATIVE PARKINSON’S DISEASE
The main issues were:
- Limited understanding of the disease etiology;
- 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 causing PD. Although more research is needed to fully understand the PD etiology, 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.
This article focuses on the types of therapeutic molecules that can be used for treating PD, keeping in mind the key requisite that such therapeutic drug has to be able to cross the BBB.
Pharmaceuticals can be classified into two types of molecules: small molecules and macromolecules. Most small molecules such as Aspirin, Motrin, and Levodopa are BBB permeable. For decades the process of drug discovery has been centered on designing, developing and selecting small molecules with activity at a particular site or receptor in the brain 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 PD 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 molecule based drugs have been plagued with lack of specificity, development of drug resistance, low therapeutic indices and frequent administration, in addition, being inept to cure the disease.
Macromolecules are large molecule modern drugs such as engineered proteins (eg: nerve growth factors), antibodies, genes, vectors, micro-RNA, Si-RNA, and ribozymes, which are otherwise effective in ex-vivo studies, 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. Similarly, micro-RNA, Si-RNA, and ribozymes are highly specific molecules but cannot cross the BBB. Although neurodegenerative diseases have been known for many decades and despite enormous research efforts both by private sectors and government institutes, there are no diagnostics and curative treatments for Alzheimer’s and Parkinson’s diseases. 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 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, modifies the disease by halting its progression.
Realizing the urgent medical need, a small La Jolla based Biotech Company, has taken upon it 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, this company first focused upon tackling one of the biggest challenges of medicine, which was to overcome the hurdles of 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 world renowned 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 has launched a program to develop BBB permeable therapeutic molecules for Parkinson’s disease. It has developed a drug to neutralize and/or modulate the function of one of the pathogenic proteins, alpha- synuclein, implicated in the pathogenesis of PD. The company is now in the process of gathering resources to advance this potential pharmaceutical to preclinical and clinical trials.
As the founder and moving force behind PRO, Jo Rosen has, for the past 22 years, fostered and promoted a better quality of life for Parkinsonians and their care givers through emotional support and education. While continuing in her role as president of PRO, and continuing the emotional and educational support mission of PRO to make sure that no one is isolated because of Parkinson’s disease, Jo has taken on a personal mission to raise funds for this exciting new research, in hopes of achieving human clinical trials for a possible cure within 12 to 18 months.
If you are, or know someone, who is an experienced, sophisticated, investor with the ability to underwrite ($100,000 or more) this expensive research, I invite you to contact Jo Rosen personally at 760-895-5161 to further discuss the details of this project, answer your questions and, hopefully inspire you to join her in funding this scientific research. The company doing the research is a for-profit company founded and run by scientific entrepreneurs.