Mexican researcher close to finding a cure for Parkinson’s disease
Published on March 25, 2015, News Medical
Responsible for the scientific finding is Gabriela Caraveo Piso, researcher at the Whitehead Institute for Biomedical Research in the United States, who discovered that the role of calcium as an intracellular messenger can become lethal to brain cells when in high concentration.
Neurological diseases called synucleinopathies, such as Parkinson’s, are characterized by the aggregation of alpha-synuclein protein. This action triggers a series of events such as the rise in intracellular calcium leading to over-activation of the enzyme calcineuria. This in turn removes phosphates (intracellular communication paths) to alter their functions and kill cells.
Gabriela Caraveo, a biologist graduated from the National Autonomous University of Mexico (UNAM), sought to nip this problem, after performing a series of analyzes in yeast, worms, and neurons of mice, found that by reducing the levels of activation of calcineurin, without eliminating it completely, the cells survived.
By modifying the activation of calcineurin contact with NFAT protein is cut out, and the communication to actin cytoskeletal rearrangements is redirected, which is responsible for cell morphology, thereby reducing failure in the motor function in animal models of Parkinson said the Mexican, who works in the lab of Susan Lindquist in the city of Cambridge, Massachusetts To achieve adequate toxicity reduction the drug tacrolimus was used, which is administered clinically in newly transplanted patients to prevent organ rejection by the immune system.
Because calcineurin is also highly expressed in brain, this immunosuppressant that can cross the blood brain barrier is able to reduce the activation of calcineurin in the brain reducing the toxic symptoms of the disease. But it is important to adjust the dosage, because too much of it completely eliminates the activation of calcineurin preventing stimulation of protective pathways like the cytoskeleton leading to cell death.
“The dosage of the drug, also called FK506, I propose is well below the level of the immunosuppressants, which allows my work to have immediate treatment of neurological diseases characterized by the aggregation of alpha-synuclein as therapeutic implications as the Parkinson’s disease,” explained the specialist in neurosciences.
In healthy people, cells achieve to regulate the amount of intracellular calcium, the problem is when there are neurological diseases such as Parkinson’s disease, the element is accumulated, becomes toxic and kills many neurons including dopaminergic neurons, responsible for implementing the motor functions.
According to preclinical results with tacrolimus pathologies associated to Parkinson’s disease decreased in rodent models. The next step is to start human trials to test its effectiveness and safety as an alternative treatment that could even act as a cure
International Stem Cell Corporation Completes Important Study in Parkinson’s Disease Program
The Wall Street Journal, June 19, 2014, 8:35 a.m.
International Stem Cell Corporation (OTCQB: ISCO), a California-based biotechnology company developing novel stem cell based therapies, announced today the completion of the acute toxicity study of the Company’s proposed clinical product to treat Parkinson’s disease. The recently completed IND-enabling study transplanting rodents with human neural stem cells, derived from ISCO’s proprietary parthenogenetic stem cell platform, showed that the cells are well tolerated even at high doses up to the equivalent of 2.2 billion cells in humans. The program continues to progress according to the plan outlined with the FDA at the pre-IND meeting as reported in February 2014. Parkinson’s disease program uses human parthenogenetic neural stem cells (hPNSC), a novel therapeutic cellular product derived from the company’s proprietary histocompatible human pluripotent stem cells. hPNSC are self-renewing multipotent cells that are precursors for the major cells of the central nervous system. The ability of hPNSC to (i) differentiate into dopaminergic (DA) neurons and (ii) express neurotrophic factors such as glial derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) to protect the nigrostriatal system, offers a new opportunity for the treatment of Parkinson’s disease, especially in cases where current small moleculeapproaches fail to adequately control the symptoms.
Largest-ever trial in Parkinson’s disease shows that for long-term treatment levodopa is better than newer drugs
Medicalxpress, June 10, 2014
The PD MED trial randomly assigned 1620 people with early PD to levodopa-sparing therapy (DA or MAOBI) or levodopa. With up to 7 years of follow-up, self-reported scores on scales measuring mobility and quality of life showed small but persistent benefits of starting treatment with levodopa rather than the other drugs. Patients in the levodopa group also reported significantly better scores on the activities of daily living, stigma, cognition, communication, and bodily discomfort scales than those taking levodopa-sparing therapy despite more involuntary muscle spasms.