Treating Alzheimers Disease with Neprilysin secreted by adipose derivedmesenchymal stem cells

Dr Steven KellnerCSO Med Cell Europe AG Switzerland

IntroductionAlzheimer’s disease (AD) is the most common cause of demen-tia, accounting for up to 70% of all dementia cases, and is nowestimated to be the third leading cause of death, after heart dis-ease and cancer. AD currently affects 5.2 million people in theUnited States (US), with projected estimates reaching 13.8 million(115 million worldwide) by the year 2050.1 Amyloid dysfunctionis known to be the main paathological reason in around 20 smi-lar diseases: Parkinson, M. Huntington, ALS and Diabetes type 2among others.

Alzheimer's DiseaseAD pathology shows accumulations of extracellular amyloid-beta(Ab) containing plaques and intracellular neurofibrillary tau tan-gles in the brain. The involvement of Ab in AD is a prerequisiteto the significance of Ab clearance to AD. It should be noted thatAb is a naturally occurring endogenous peptide that may havenormal physiological functions. Pathology associated with Ab isrelated to its aberrant accumulation/aggregation. The proteolyticdegradation of Ab is a major route of clearance. Of these enzymes,neprilysin(NEP) is considered one of the most important for thecontrol of cerebral Ab levels.2

Neprilysin from adipose derived mes-enchymal stem cells ad-MSCNEP, a 90±110-kDa plasma membrane glycoprotein, is the proto-type and best-characterized member of the M13 zinc metallopep-tidase family. NEP is primarily expressed in the kidney, howev-er, it occurs at much lower levels in many other tissues, includingbrain, where it is located on neuronal membranes, both pre- andpostsynaptically.3 Neprilysin occurs naturally in the secretome ofthe ad-MSC, which is produced in vitro and in vivo as a meansof communication from cell to cells and as a reaction to externalinfluences. The secretome of ad-MSC can be harvested as a clinical grade treatment for

various illnesses.

Patented system to augment Neprilysin inthe secretomePretreatment of ad-MSC achieved elevated levels of Neprilysinwithout compromising the other active ingredients of the secre-tome.

Simple differences in stem cell cultivation will change levels ofneprilysin in the secretome.

Future perspectivesTwo of the major neuropathological hallmarks of AD, senileplaques and neurofibrillary tangles, take place with the aging ofthe human brain many years prior to the disease onset.This sug-gests that aging is the predominant

risk factor for AD, and that a large number of people enteringan old age and manifesting these neuropathological structures intheir brains are likely to be in a presymptomatic stage of MCI andAD. In this respect, it is most

important that a preventive medicine combined with presymp-tomatic diagnosis allows a substantial portion of aged people toescape from the scourge of dementing syndromes. 4 There havebeen an overwhelming

number of reports indicating that neprilysin expression/activi-ty declines with aging and in AD. Substitution with the secre-tom from adipose derived mesenchymal stem cells containingneprilysin should be able to prevent AD and maybe even reverseexisting amyloid accumulation.

ReferencesRef.1 CSF Biomarkers of Alzheimer’s Disease: Impact on DiseaseConcept, Diagnosis, and Clinical Trial Design. Anne M. Fagan,Advances in Geriatrics, Volume 2014, Article ID 302712

Ref.2 Amyloid-beta and Alzheimer’s disease: the role ofneprilysin-2 in amyloid-beta clearance. Robert A. Marr andDaniel M. Hafez, Frontiers in Aging Neuroscience, August 2014| Volume 6 | Article 187

Ref.3 b-Amyloid catabolism: roles for neprilysin (NEP) and othermetallopeptidases? Julie A. Carson and Anthony J. Turner, Jour-nal of Neurochemistry, 2002, 81, 1-8

Ref.4 Metabolism of amyloid O peptide and pathogenesis ofAlzheimer’s disease. Takaomi C. SAIDO, Proc. Jpn. Acad., Ser. B89 (2013)