Research in 2008 had indicated Russian antihistamine drug Dimebon could be the cure to Alzheimer. In 2010, some studies disproved this. But the drug may still have a shot at being the cure for all types of dementia including Alzheimer’s. Early research had suggested this medicine prevented the protein accumulation that causes dementia symptoms. Work on the drug slowed down in 2010-2012 however. This was the year a Phase 3 clinical trial testing the effect of the drug on dementia was found to be ineffective.
Research indicates this medicine should continue to be useful. Researchers are currently investigating the biomechanism underlying the drug in nerve cells of mice with dementia. Research methods are being used to locate which part of the cell Dimebon targets and how this yields a protective impact. Modified drugs are being tested as well, so as to check the impact of these too.
Dimebon effects the underlying mechanism of Alzheimer’s dementia, according to some researchers. Scientists have found that it reduced Alzheimer’s linked impact of the hallmark protein tau in rodents displaying this dementia.Modified forms of Dimebon reduce the effect too. The results, however, are most potent with Dimebon in its unmodified form.
Despite the earlier results, researchers believe Dimebon has a future when it comes to treating Alzheimer’s. However, scientists now hold that it may work only at a certain phase of dementia in conjunction with other forms of therapy. While there is lack of clarity regarding the role Dimebon has in impacting the cell, there is some movement forward in understanding how the drug could work and making improvements leading to better treatment for Alzheimer’s, a progressive dementia that currently has no cure.
The 2008 Study
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Dimebon is a Russian antihistamine discovered 25 years ago. In 2008, when it comes proved in an 18-month trial to be an effective cure for Alzheimer’s, experts were surprised. This was positive news after the failure of Flurizan, once considered a popular cure for Alzheimer’s. The Russian researchers found the drug to be effective against mild Alzheimer’s in 183 patients. Dimebon has stabilized disease for a minimum of 18 months, Overall, patients treated with this drug tended to have better or marginally improved mental functioning.
This difference between test and placebo subjects was the biggest seen in Alzheimer’s patients. While placebo patients declined, those having taken Dimebon were sharper than ever on behavior, cognitive functioning and memory. However, a NY geriatric psychiatrist Gary Kennedy warned against the drug, saying it will not work as US patients get different care. Patients actual improvements were, in fact, not different from current Alzheimer drugs like Exelon, Razadyne, and Aricept. What has generated excitement, however, is the fact that the medication operates in a mechanism different from other Alzheimer’s drugs. This medication could be combined with existing medicines to slow down the disease course. The Dimebon data was encouraging at this point. However, it had not been verified by American and West European research.
How Does Dimebon Work?
Dimebon’s precise mechanisms of action are not known.Research, however, shows that it impacts the powerhouse of the cells, the mitochondria. This combats a defect that destroys brain cells. This is why Dimebon has even found to be effective in treating patients with Huntingdon’s disease. However, it is important to remember that plaque is not the only problem dementia patients face. There is a generation of fibrous tangles, made of a protein referred to as tau. These tangles impact the brain before symptoms surface, and the higher the number of tangles, the more serious the disease gets.
Development of anti-tangle drugs and anti-plaque drugs like Remember and PBT2 seek to prevent this from happening. The new drug Dimebon reversed the symptoms of the degenerative disease. The effect on cognitive functions seemed to increase over time. The most encouraging part about Dimebon was that it worked for a year, whereas current Alzheimer’s drugs work for only 3-6 months.
Dimebon has been shown to improve memory and skills to take on tasks like making a call or shopping. While there are 2 major classes of dementia drugs, researchers think Dimebon targets both.
The Failure of the Drug: 2010-2012 Research Trials
Photo By: Pexels/ CC BYPfizer in 2012 announced the Dimebon medication had failed an important test. Results were obtained from the FDA approved Phase 3 clinical trial named CONNECTION run by Pfizer and its subsidiary firm Medvation.
Phase 3 is the specific stage in research for studying the impact of drugs for human use. Following animal studies, the first phase establishes doses and safety of medicines in human beings. The Phase 2 trials check to see if the medication works on smaller groups of patients. Phase 3 is the final phase when the drug is tested on a multitude of people and results are safeguarded by testing using double-blind designs and placebos.
The Phase 3 study which marked the apparent failure of Dimebon was noted in 600 patients suffering moderate AD in EU and the US. Patients were randomly assigned to Dimebon or a sugar pill. During this time, their cognitive function was assessed to determine the changes occurring. Findings unearthed that patients receiving Dimebon did not differ from placebos.
The remarkable results obtained in 2008 were consistent with the findings of animal studies. Dimebon had been found to replicate the effects of classes of drugs currently approved by the FDA for treating dementia.
It blocks pathological activity at NMDA receptors in the brain, as does FDA approved memantine. It blocks the breakdown of enzymes of the chemical messenger acetylcholine just like drugs like Aricept. Dimebon also helps prevent the abnormal protein tau’s buildup associated with tangles in dementia patients’ brains. It may even block abnormal protein amyloid that builds up in dementia patients.
Dimebon is, however, no longer a miracle cure for dementias like AD. The quest for medicines that enhance the cognitive functioning of AD continue. Also known as latrepirdine, it was sold as an antihistamine in Russia in the 1980s. In the 1990s, Russian scientist Sergey Bachurin first discovered Dimebon could be used to treat AD.
Why Study Results Differed?
Authors of the 2008 Russian study held that their patients were younger than those recruited for the CONNECTION study. The mean baseline mini-mental state exam score was 17.7 for phase 3 subjects as against 18.7 for phase 2. Additionally, the 2008 study saw a massive decline in control subjects, while no such differences were noted between experimental and control group subjects in the phase 3 study. Comments were also raised about the validity of the Russian study. Equally important was whether the multinational study had recruited typical patients, with more than 40% recruited from the US. There were many other differences between the phase 2 and 3 studied.
The Future of Dimebon
Photo By: Pixabay/ CC BYNegative Phase 3 studied have led to a fall in clinical trial programs. But a current study is comparing Dimebon with placebos in 1050 patients. Another study at the Mount Sinai School of medicine and international research groups is generating stunning results through Dimebon in animal studies when the neurodegenerative disease is detected at early stages.
This 2014 study was published in the journal Molecular Psychiatry. Its roots were laid in the failure of the 2010-2012 study. The new study is being led by researcher Sam Gandy who is director of the MS Center for Cognitive Health. In this trial of studies, latrepridine was given along with a placebo at early stages of AD in mice. Research showed that Dimebon stopped the loss of memory and progression of neuropathology. Additionally, Dimebon also revved up the autophagy phase, which prevents the neurodegeneration of the brain. This time, researchers are seeking to definitively test Dimebon on early-stage AD. Clearly, Dimebon has a bright future as a treatment for Alzheimer’s, if the Phase 3 clinical trials are successful this time.