The present invention relates to a pharmaceutical composition for treating cerebral atrophy associated disease.
Alzheimer's Disease, also known as senile dementia disease, has become a global epidemic as the aging population increases rapidly. According to the International Association dementia statistics, there are 46.8 million global dementia patients in 2015, and one person suffering from dementia disease every 3 seconds. It is expected the global dementia patients will be twice in 2030, thus, how to prevent and treat dementia disease is an important issue.
Dementia disease is a chronic, progressive degenerative disease, can be divided into two categories: degenerative dementia and vascular dementia disease. The majority of patients are degenerative dementia, wherein the Alzheimer's disease, frontotemporal lobe degeneration, and Dementia with Lewy Bodies are the most common disease.
Vascular dementia disease is caused by stroke or cerebral vascular disease, the mental retardation is also caused by brain cell death due to poor blood circulation in the brain. Symptoms of early dementia may include: irritability, aggression, inability to normal speech, easy to get lost, emotional instability, loss of motivation to survive, loss of long-term memory, difficult to remember the recent occurrence, difficult to take care of themselves and behavioral abnormalities. Therefore, when the patient's condition deteriorates, they often begin to leave the family and social relations, and the gradual loss of physical function, then leading to death.
In the current study of dementia prevention is mainly focus on Alzheimer's disease. Although the true cause of Alzheimer's disease is still unknown, the abnormal accumulation of beta-amyloid, neurofibrillary tangles, and extensive neuro-inflammation, are the main pathological features, and so as cause serious impact on nerve repair and regeneration function.
The current treatment of dementia, mainly using acetylcholine inhibitor (acetyl-cholinesterase inhibitor) or NMDA receptor antagonist (NMDA anatagonist) to delay the development of the disease or improve the patient's mental and behavioral symptoms. However, the drugs cannot effectively prevent or restore damaged brain cells, in addition, the above-mentioned drugs on the patients themselves have convulsions, dyspnea and other side effects. Therefore, there is still a need for better medical treatment to treat the dementia disease.
Accordingly, the present invention provides a pharmaceutical composition for treating cerebral atrophy associated disease. Said pharmaceutical composition comprising adipose-derived stem cells, can improve the function of excitatory synapses in dementia patients and improve the function of memory storage area in brain.
The present invention provides a method for treating cerebral atrophy associated disease in a subject, wherein the method comprising administering to said subject a pharmaceutical composition, wherein the pharmaceutical composition is having an adipose-derived stem cell.
In one embodiment, the treating cerebral atrophy associated disease is through improving the function of memory storage area in brain of dementia patients.
In one embodiment, the treating cerebral atrophy associated disease is through increasing the function of excitatory synapses in dementia patients.
In one embodiment, the treating cerebral atrophy associated disease is through increasing the numbers of pyramidal neuron synapses in the cerebral prefrontal cortex in dementia patients.
In one embodiment, the treating cerebral atrophy associated disease is through increasing the numbers of pyramidal neuron synapses in the hippocampus in dementia patients.
In one embodiment, the concentration of the adipose-derived stem cells is 6×104/ul˜7×104/ul.
In one embodiment, the pharmaceutical composition is implanted near the fornix area in right cerebral hemisphere, wherein AP is −0.2, ML is −0.5 and DV is −6.
Adipose-derived stein cells (ADSCs) of the present invention are mesenchymal stem cells (MSC) in adipose tissue, which can be obtained from liposuction or lipectomy. That means, it is easy and convenient to obtain the adipose-derived stem cells without causing trauma in patients. Besides, the adipose-derived stein cells can be autologous implanted, which is easily be compatible, so as to reduce the anti-rejection drugs, long-term in vitro culture and other shortcomings. Furthermore, the adipose-derived stem cells are easy to isolate and can be rapidly and stably amplified in vitro, and are also less susceptible to aging, thus being suitable for use as pharmaceutical compositions of the present invention.
Experimental Animals
The Wistar rats are divided into three groups: control group, dementia group and experimental group, 300 pmole Amyloid-β-protein is implanted daily into the rats in dementia group and experimental group in day 0-28, the implantment position is AP: 0.4, ML: 1.5, DV: 3.3 so as to cause dementia disease. The pharmaceutical composition of the present invention (containing 1×106/15 ul adipose-derived stem cells, which is 6×104/ul˜7×104/ul adipose-derived stem cells) is implanted into the rat brain of experimental group in day 14, the implantment position is near the fornix area in right cerebral hemisphere (AP: −0.2, ML: −0.5, DV: −6) and the rat brain in control group is punctures in day 14.
The rat brain of control group and dementia group is stained by anti-Aβ 1-42 antibody. Please refer to
The rats of experimental group is implanted with the pharmaceutical composition of the present invention, and then sacrificed in day 3 (
In
The rats in control group, dementia group and experimental group were placed in a Morris water maze for 5 days to observe the movement patterns of rats in each group for the test of spatial memory. Please refer to
The rat brain of control group, dementia group and experimental group rats were analyzed by Western-style dot-blot method using the antibody of synaptic density protein 95 (PSD-95). The level of glutamatergic postsynaptic in the brain of the rat is shown in
As shown in
The neurons in the control group, dementia group and experimental group rats were labeled with Lucifer yellow to analyze the density of nerve dendrites in the brain of each group.
Statistical results is shown in
From the above results, the pharmaceutical composition of the present invention can effectively increase the density of nerve dendrites of dementia patients.
Although the present invention has been described in terms of specific exemplary embodiments and examples, it will be appreciated that the embodiments disclosed herein are for illustrative purposes only and various modifications and alterations might be made by those skilled in the art without departing from the spirit and scope of the invention as set forth in the following claims.
This Non-provisional application claims priority under 35 U.S.C. §119(a) on Patent Application No(s). [62/321,946] filed in American United States Apr. 13, 2016, the entire contents of which are hereby incorporated by reference.
Number | Date | Country | |
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62321946 | Apr 2016 | US |