Phase I = Animal testing
Phase II = Placebo and meds
Phase III = Just the meds, to see how they work
A medical procedure whereby Human Bone Marrow/ Shark Stem Cells are transplanted into a patient. These cellular building blocks are usually administered intravenously and subcutaneously (under the skin). It is a painless procedure, which takes place in approximately one hour, and has no negative side effects.
The Bone Marrow/ Shark Stem Cell searches out, detects and then attempts to repair any damage or deficiency discovered, as well as releases growth factors, which stimulate the body's own repair mechanisms.
They can treat with Human Bone Marrow/shark, including children and adults suffering from many of mankind’s most devastating diseases.
HART is going, into a phase III, trail.
The Huntington Study Group (HSG) is conducting a study of the research medication ACR16 in persons 30 years of age and older who have clinical features of Huntington Disease (HD). HART is designed to determine the general safety and tolerability and an effective dose of ACR16 as well as the effect of ACR16 on motor (movement) and cognitive (thinking) abilities in subjects with HD. Approximately 35 research centers in North America will enroll up to 220 subjects for 16 weeks each. Enrollment began in October 2008. This Phase IIB study is sponsored by NeuroSearch Sweden AB. My Brother and I want to get into the JHD Study. It will happen, after the Adults, are found, to be okay. This the number one study, that we want, to be in.
ACR16 belongs to a novel class of agents called dopaminergic stabilizers, which have the ability to either enhance or inhibit dopamine controlled functions depending upon the initial level of dopaminergic activity. ACR16 was previously evaluated in four clinical Phase I/II studies for Huntington's Disease, Parkinson's Disease and psychosis and demonstrated a good safety and tolerability profile. In a Phase II study with Huntington's Disease, the results showed that 28 days of treatment with ACR16 led to an improvement in the patients' voluntary movements, including Parkinsonism and gait.
Dimebolin is safe and well tolerated, and provides significant improvements in cognition for patients with mild to moderate Huntington's disease, according to research presented here at the 9th International Conference on Alzheimer's and Parkinson's Diseases (ADPD).
He indicated, "[Dimebolin] was developed originally as an antihistamine ... and then studied in Alzheimer's disease," where it was shown to improve patient cognition, behaviour, and overall function.
Huntington's disease is a neurodegenerative disease of midlife that is also characterised by cognitive impairment and behavioural changes. Dr. Kieburtz and colleagues conducted their study to evaluate the safety and tolerability of dimebolin, and to explore its effects on symptoms of Huntington's disease.
They enrolled 91 patients with mild to moderate Huntington's disease and total functional capacity of 5 or greater. Of these patients, 45 were randomised to placebo (mean age, 52.7 years; male, 40.0%) and 46 to dimebolin 20 mg TID (mean age, 53.7 years; male, 6.5%), all receiving treatment for 90 days.
Dimebolin was as well tolerated as placebo among patients who completed the treatment course at the target dose (87% vs 82%, respectively), with fewer patients reporting adverse events (70% vs 80%).
Dr. Kieburtz concluded, "[Dimebolin] is safe and well tolerated, at least over this 3-month period of observation, ... and if you sort out the people who actually had cognitive impairment at baseline, it is the MMSE that shows a significant change."
He also noted the lack of effects in the other measures, "because really these cognitive measures are intended to track long-term deterioration rather than short-term improvement, with the ADAS-cog measuring aspects of cognition that aren't key to Huntington's disease."
I want this to work, and cure my dementia.
Ethyl EPA is a purified version of eicosapentaenoic acid, an Omega 3 fatty acid found in fish oil. A Phase III clinical trial managed by the Huntington Study Group and sponsored by Amarin Pharmaceuticals was suggestive of benefit after six months of use but not conclusive. There may be an additional trial to resolve the issue.
Blocking or stabilizing the neurotransmitter dopamine has been shown to reduce chorea. In addition, there is evidence to suggest that normal amounts of dopamine may be toxic in the brain in Huntington’s Disease.
Tauroursodeoxycholic acid or TUDCA is an endogenous bile acid which inhibits mitochondrial apoptosis. It is currently in Phase I trials sponsored by the HSG; results are expected soon.
The excitotoxicity theory holds that neurons are abnormally sensitive to glutamate; overstimulation by this important neurotransmitter can lead to cell death.
Brain derived neurotrophic factor (BDNF) protects brain cells and promotes neurogenesis, the growth of new ones. Levels of BDNF are known to be reduced in the brains of HD patients. SSRI (selective serotonic reuptake inhibitor) antidepressants are known to elevate BDNF and one such antidepressant, Celexa, is in Phase II clinical trials. In addition, Cortex pharmaceuticals has an ampakine in preclinical testing which also induces BDNF. Raptor Pharmaceuticals is planning a Phase II trial of delayed release cysteamine later in 2008.
In addition to BDNF, researchers are also looking at other neurotrophic factors and synthetic compounds that mimic their effects with the hope that they will be neuroprotective in HD patients. One candidate is fibroblast growth factor 2 which promoted neurogenesis and extended survival time in the R6/2 mice. It is still in preclinical testing.
Ceregene has developed a viral vector for delivering a gene for the neurotrophic factor neurturin into the brain. This potential treatment is in Phase II clinical trials for Parkinson’s Disease and preclinical testing for Huntington’s Disease.
Trophos has a lead candidate which is neuroprotective in a striatal cell model of HD.
The dysregulation of gene transcription has been shown to be a significant problem in Huntington’s Disease. The HD protein interferes with the normal expression of genes. Histone deacetylase inhibitors may be able to reverse or partially reverse this dysfunction. Envivo has a candidate drug which performed well in preformed well in preclinical testing and a Phase I clinical trial is planned for later in 2008
Huntington’s disease is a disease of aging in that cells in the areas of the brain that are affected by HD are for some time able to cope with the challenges presented by the mutant protein. As we age, our cellular defense mechanisms become less efficient. There is a group of genes called sirtuins which appear to regulate aging. In the spring of 2008 Sirtris Pharmaceuticals announced that there is new data showing that in a preclinical model of Huntington's disease, mice live longer and have less disease pathology in the brain with increased SIRT1 expression. Sirtris has several compounds with induce SIRT1 expression. I use healthy chocolate, Sea salt, and green tea with orange juice.
One problem that increases with aging which is thought to be particularly damaging in HD is oxidative stress. During energy metabolism, free radicals of oxygen are produced which can damage proteins, lipids, and DNA if there aren’t enough antioxidants available with which to bond. As mentioned above, creatine and CoQ10 are antioxidants. Intellect Neurosciences is doing preclinical studies with their synthetic version of Indole-3-propionic acid.
The normal huntingtin’s protein is cleared away from the cell through the ubuiqitin proteosome system. This housekeeping process is not effective with the HD version of the protein. There is an alternate way to clear away the HD protein called autophagy. Two drugs which are already approved were found to be induce autophagy in cell and drosophila models. The next step is to test these drugs in the HD mice.
Both excess copper and excess iron have been shown to contribute to HD pathology. Pipex Pharmaceuticals, in collaboration with researchers at the VA Medical Center at Ann Arbor, is doing preclinical testing of their copper chelator. Varinel, an Israel Pharmaceutical company is testing their copper chelator in HD mouse models with funding from CHDI.
Research shows that there is an aberrant amplification of the adenosine 2A receptor signaling in striatal cells in people with Huntington's Disease. Kyowa Pharmaceuticals has an A2A receptor antagonist called KW-6002 (istradefyllin) that is in clinical testing for Parkinson’s disease.
When an HD mouse model was engineered to be resistant to caspase 6, the HD protein was not cleaved, the protein did not accumulate in the nucleus of the cell, and the mice did not develop Huntington’s Disease. CHDI is funding the development of a safe and effective caspase 6 inhibitor.
If the HD gene could be stopped from expressing itself, the result could be a virtual cure. Two pharmaceutical companies, Sirna and Anylam are working on ways to interference with messenger RNA so that instructions to make the HD protein are not sent out. An issue is that it may be necessary to develop allele specific ways to do this so that only the HD protein is shut down and the normal huntingtin’s protein continues to be expressed. The antisense approach being taken by Isis is somewhat different in that it is possible for a drug to do this on a periodic basis; the goal is to find an optimal time in which the cell can recover from the HD protein without being harmed by the absence of the normal protein.
Research with the HD mice suggests that stopping the HD gene from expressing itself would result in improvement even well into the progression of the disease. However, restorative treatments will likely be necessary for full recovery of later stage patients. ReNeuron has a line of stem cells which has shown efficacy in a cell model of HD. Preclinical work is being done.
