ICBII Update on the Road to the Cure - July 2022Category: Road to the Cure
A Real-Time Science Report
Ram S. Bhatt, PhD., Chief Science Officer
The Role of LRRK2 in Parkinson’s disease – Mutations in the leucine-rich repeat kinase 2 (LRRK2, PARK8) gene are the most common cause of familial Parkinson’s. The most common LRRK2 mutation is G2019S meaning that the normal glycine residue at position 2019 is converted to serine in the natural LRRK2 protein. This mutation accounts for the 5-6% of familial and 1-2% of Parkinson’s cases whose cause is not known (idiopathic Parkinson’s). LRRK2 Parkinson’s patients display clinical features that are largely indistinguishable from the idiopathic Parkinson’s and similar neuropathological features. Most brains with LRRK2 mutations display dopaminergic neuronal loss in the substantia nigra region accompanied by typical brainstem Lewy body pathology. A small portion of LRRK2 mutation brains show heterogeneous neuropathology, including diffuse Lewy bodies, tau-positive neurofibrillary tangle pathology, and TDP-43 positive inclusions.
Approaches to Treat Parkinson’s disease – Whether it is familial or idiopathic Parkinson’s the dopamine producing neurons in the substantia nigra part of the brain are compromised affecting motor symptoms such as movement, balance, gait, and muscle control. The non-motor symptoms include anxiety, depression, cognition dysfunction, hallucinations, insomnia, bladder hyperreflexia, soft speech, swallowing issues, and loss of autonomous system. The pathological hallmark of the disease is the presence of Lewy bodies containing increased levels of alpha-synuclein, neurofilaments, and glial cells across the array of brain regions. Despite intense efforts for many decades, the fundamental mechanisms behind loss of dopamine producing neurons are still unknown.
The scientific and medical community around the globe is working diligently to develop technology to restore the dopamine producing neurons. We will discuss one such technology this month. The remaining technologies will be discussed in future issues.
Stem Cell Therapy – Cell replacement therapy with embryonic stem cells and human-induced Pluripotent Stem Cell (iPS) to restore dopaminergic neurons in patient’s brain has been pursued for nearly 3–4 decades. Although a very promising approach, issues such as quality control of stem cells, the ability of transplanted cells to produce dopamine, transplant rejection in case of embryonic stem cells, poor cell survival, graft induced dyskinesia, and risk of tumor formation are persisting as well as ethical issues of obtaining stem cells from embryos. Although the researchers working on stem cells think they have addressed most of those issues, the jury is still out about the efficacy of cell replacement therapy. Dr. Jeff Bronstein, a neurologist at UCLA, has treated hundreds of Parkinson’s patients over the years, including four who were part of the fetal transplant trials. One, Dr. Bronstein says, “had a transplant that probably took hold, given that the patient was on a minimum dose of levodopa for 20 years afterwards. Yet he was still falling frequently and had advanced dementia. He was a successful patient, but the disease keeps progressing”. Bronstein continued to say “The mistake people make is that they look at stem cell transplantation as disease-modifying therapy. It is not. It has the potential to improve disease symptoms, but it cannot alter the course of the disease.”
In subsequent articles we will be covering other available technologies for the treatment of Parkinson’s as well as what ICBII is doing to rejuvenate the dopamine neurons.
PRO would appreciate knowing what subjects you would like Dr. Bhatt and the scientists at ICBII to cover in this column.
ADDITIONALLY, WOULD YOU LIKE TO HELP get ICBII’s drugs to market faster? The joy of being a part of these historical events can be had by helping ICBII 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 ICBII 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.
- Previous Article
- Message from the President - July 2022