Amylovis: For Early Imaging Diagnosis and Treatment of Alzheimer’s Disease
To evaluate Amylovis for early diagnosis and treatment of Alzheimer's disease.
Alzheimer’s disease (AD) is a typical disease of the elderly. Several studies have been made to estimate the prevalence of this disease. It was stated in a meta-analysis, that about 25.5 million people worldwide suffered from dementia in 2000 year, with a prognosis of 63 million in 2030 and 114 million in 2050, being Alzheimer’s disease the most common type of dementia, accounting for 60-70% of all cases. According to a meta- analysis of the magazine “The Lancet” , in China, the world 's most populous country , the number of people with dementia increased from 3.7 million in 1990 to 9.2 million in 2010. With the continued growth of aging of China's population, these findings suggest that the nation is headed to a larger than expected load of dementia. The China´s Project of Alzheimer (called CAP) estimates that 75% of urban patients have not been diagnosed in a timely manner. The proportion of those not diagnosed in rural areas is probably higher. It happens despite the fact that there is growing awareness of these diseases. As the number of AD-patients will increase in the future, the burden on society for the healthcare of these patients will be enormous. The impact of dementias on the economies of the countries is not sufficiently appreciated.
According to statistics from the Alzheimer's disease International (ADI), the total cost worldwide of dementias were $ 604 billion in 2010. If dementia were a country, it would be 18 in the world economy, ranking between Turkey and Indonesia. Today, it is known that Alzheimer's disease is characterized pathologically by the presence of senile plaques (SP) and neurofibrillary tangles (NFT). The diagnosis of the AD is made post-mortem by a neuropathological examination with the appearance of SPs and NFTs in the brain. On the other hand, the clinical diagnosis of AD has moderate reliability. Early diagnosis of AD is very important in order to maximize the efficacy of potential therapies in initial stages of the disease and to improve the efficiency of clinical trials of new therapeutic drugs. Neuroimaging methods have increased the horizons for the diagnosis of brain disorders by means of techniques such as magnetic resonance imaging (MRI), single-photon computed tomography (SPECT) and positron emission tomography (PET). For example, some compound labeled with positron-emitter radionuclides have been proposed as radiotracers for early detection of senile plaques in patients. The Neuroscience Center of Cuba has a set of compounds called Amylovis, which are related to the SP and have the advantage of being versatile in radiolabeling. Thus, these compounds can be labeled independently with different types of radionuclides, both gamma ray emitters (99mTc, 123I or 131I) and with positron emitters (18F and 11C). Therefore, the Amylovis compounds could be adapted to the equipment possibilities (PET, SPECT and MRI) in a health center.
In addition, it was found in vitro evaluations that some of the Amylovis compounds modulated the kinetic of the protein fibrilgenesis process, which was confirmed by microscopic techniques.
Also, the compounds showed cytoprotective activity in cultures of cerebellar granule cells exposed to cytotoxic stimuli, evidenced by tests of cell viability and apoptosis.
Figure 1 In vitro studies. Micrographs of Transmission electronic and Atomic Force microscopies (TEM and AFM) confirm the disaggregating effect on pre formed β-fibrils by Amylovis® compounds.
Patent granted Cu/P/2009/57, EP 2 436 666 A20, South Africa P58243za00. Method for obtaining new naphthalene derivatives for in vivo diagnosis of Alzheimer's disease.
Patent granted Cuban CU/P/2013/27: "New naphthalene derivatives and their preparation processes for in vivo diagnosis of Alzheimer's disease through imaging techniques "
Requested Patent 4-9-2014. PCT/CU2013/000009, WO2014131374 A1. Chemical chaperonins as novel molecular modulators of beta protein aggregation present in conformational disease.
There are compounds have been evaluated in vitro preclinical assays to be used as therapeutic agents and diagnosticians. Preclinical in vivo studies are being carried out.
Figure 2 PET images of 18F-Amylovis® which cross the BBB, whether in healthy animals as well as in AD animal model. Left: Images of a control mouse CadizWT13. Right: Images of a transgenic mouse CadizTG73. 6 Images obtained after 120 s of the 6b inject
REQUESTED KIND OF COLLABORATION
These patents claim more than 100 compounds and have the competitive advantage of not having any interference with other patents published, so it keeps its novelty and inventiveness so it has a strong know-how associated. Therefore, patents are current and valid for which the product has commercial potential for diagnosis and treatment of AD.
The compounds described in the patent are versatile precursors which allow marking, independently, with more than one radionuclide for SPECT and PET, which gives an additional attraction. Also, some compounds with 19F may be used in MRI studies, as contrast agents
The granted patents have priority date 2009, so they have a window of opportunity of 14 years, with the possibility of making modifications to extend their lifetime.
Currently, early diagnosis by visualization of pathological structures for PET imaging is being performed with three products: Flutemetamol F 18 (Vizamyl), Florbetapir (Amyvid) and Florbetaben (Neuraceq), which are FDA approved.
Neurosciences Center of Cuba, Calle. 190 e/ 25 y 27, Cubanacán, Playa. La Habana. PC 11600, Phone: (+53) 7263-7100.
Key Lab for Neuroinformation, University of Electronic Sciences and Technology of China UESTC. Sichuan, Chengdu 610054, China.
Chryslaine Rodriguez-Tanty, Ph.D.
Head of Neurochemistry Department
Dr. Juan Feng
No. 4, Sections 2, North Jianshe Road,
Chengdu, 610054, China
Tel: 015255140281 (Germany)
Lixia Tang, PhD.
Senior Professor in Advanced Molecular Biology